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Planta

, Volume 248, Issue 3, pp 519–544 | Cite as

Recent advances in steroidal saponins biosynthesis and in vitro production

  • Swati Upadhyay
  • Gajendra Singh Jeena
  • Shikha
  • Rakesh Kumar Shukla
Review

Abstract

Main conclusion

Steroidal saponins exhibited numerous pharmacological activities due to the modification of their backbone by different cytochrome P450s (P450) and UDP glycosyltransferases (UGTs). Plant-derived steroidal saponins are not sufficient for utilizing them for commercial purpose so in vitro production of saponin by tissue culture, root culture, embryo culture, etc, is necessary for its large-scale production.

Saponin glycosides are the important class of plant secondary metabolites, which consists of either steroidal or terpenoidal backbone. Due to the existence of a wide range of medicinal properties, saponin glycosides are pharmacologically very important. This review is focused on important medicinal properties of steroidal saponin, its occurrence, and biosynthesis. In addition to this, some recently identified plants containing steroidal saponins in different parts were summarized. The high throughput transcriptome sequencing approach elaborates our understanding related to the secondary metabolic pathway and its regulation even in the absence of adequate genomic information of non-model plants. The aim of this review is to encapsulate the information related to applications of steroidal saponin and its biosynthetic enzymes specially P450s and UGTs that are involved at later stage modifications of saponin backbone. Lastly, we discussed the in vitro production of steroidal saponin as the plant-based production of saponin is time-consuming and yield a limited amount of saponins. A large amount of plant material has been used to increase the production of steroidal saponin by employing in vitro culture technique, which has received a lot of attention in past two decades and provides a way to conserve medicinal plants as well as to escape them for being endangered.

Keywords

Metabolites P450 UGTs Transcriptome Pathway 

Introduction

Majority of higher plants and microbes synthesize useful secondary metabolites, which are categorized into alkaloids, terpenoids, polyphenols, polyketides, etc., according to their chemical structures and biosynthetic routes. These compounds protect plants from pathogens, competitors and UV light. They also assist in plant adaptation and most of them have valuable medicinal properties that make them useful in pharmaceutical, agrochemical, flavor and aroma industries. Saponins are important plant secondary metabolites generally known for their multiple pharmacological properties (Williams and Gong 2007).

The word saponin is derived from sapo, i.e., soap, which describes the soapy appearance of saponin when combined with water. Due to their amphiphilic properties and tendency to form the foam, they can be used as surfactant or emulsifying agents (Kime et al. 2015). Structurally, saponins are amphiphilic molecules that are composed of one or more hydrophilic sugar residues and hydrophobic steroidal or triterpenoidal part on the basis of which they are called as steroidal saponin or triterpenoidal saponins. The non-sugar water-insoluble part is called as sapogenin, and on the basis of sugar present in saponin molecules they can be either monodesmosidic (contains only one sugar residue), bidesmosidic (contains two sugar residues) or polydesmosidic (more than two sugar residues) saponins (Lorent et al. 2014). Structural variants of saponin are found in plants due to the presence of different sugar at different position and orientation. The most common sugars residues that are found in saponins are d-glucose, d-galactose, l-rhamnose, l-arabinose, d-glucuronic acid, d-fucose and d-xylose (Lorent et al. 2014).

Saponins are synthesized from 30-carbon linear precursor molecule 2, 3-oxidosqualene, but during the synthesis of steroidal aglycone, there is a loss of three methyl groups that results in the formation of a skeleton having 27 carbon atoms while during synthesis of triterpenoidal aglycone all the 30 carbon atoms retains in its backbone (Moses et al. 2014a, b; Jeena et al. 2017). Steroidal saponins are further classified into two subfamilies, i.e., spirostanol saponins and furostanol saponins. Spirostanol saponins contain a bicyclic spiroacetal moiety at 22nd carbon that involves the steroid E and F rings while furostanol saponins bear a hemiacetal, methyl acetal, or Δ20(22)-unsaturation at this position (Fig. 1) (Challinor and De Voss 2013). Both spirostanol and furostanol saponins have either R or S configuration at 25th carbon position (Masullo et al. 2016). Infrared (IR) spectroscopy has been used to differentiate between spirostanol and furostanol saponins. Spirostanol possesses characteristic absorption peaks at around 980, 920, 900, and 860 cm−1 (Challinor et al. 2012a, b, c). The relative intensities at 920 and 900 cm−1 bands are predictive C-25S and C-25R configuration in spirostanol (Jones et al. 1953) but the detection of the stereochemistry of C-25 in furostanol saponins is more challenging due to the absence of ring configuration as observed in spirostanol saponins. So the conversion of furostanol saponin to the corresponding spirostanol form by either hydrolysis or by enzymatic cleavage of glucose moiety at 26th carbon position for ring closure of its side chain is the most authentic method for prediction of C-25 configuration in furostanol saponin (Inoue et al. 1996). In this review, we will focus on the steroidal saponin-producing plants whose transcriptome sequencing has been done along with we encapsulate the information related to diverse applications of steroidal saponin and its biosynthetic enzymes specifically P450s and UGTs that are involved at later step modification of saponin backbone.
Fig. 1

Structural chemical backbone of steroidal saponins: a furostanol type steroidal saponin b spirostanol type steroidal saponin. Both furostanol and spirostanol type of steroidal saponins are derived from either the 30-carbon linear precursor 2, 3-oxidosqualene (cycloartenol pathway) or 22,26-dihydroxycholesterol (cholesterol pathway) but during the synthesis of their steroidal aglycone loss of three methyl groups results in a 27-carbon backbone. Conversion of furostanol saponin into spirostanol form and vice versa is catalyzed by furostanol glycoside 26-O-β-glucosidase (F26G) and UGT glucosyltransferase enzyme, respectively

The value of steroidal saponins

Steroidal saponins obtained from Dioscorea zingiberensis are widely used for preventing cardiovascular diseases (Qin et al. 2009). In addition to providing cardiovascular protection, steroidal saponin isolated from Ophiopogon japonicus plant also exhibited various other pharmacological activities, such as anticancer, immunomodulation, anti-oxidation, anti-inflammation, cough relief, antimicrobial, and anti-diabetes (Chen et al. 2016). Steroidal saponin constituents from Paris species are used to treat cancer, malignant boil, bleeding and gastritis (Wang et al. 2015a, b, c). They also exhibited antifungal activity (Morrissey and Osbourn 1999) and used as an efficient natural sweetener like glycyrrhizin from licorice roots (Kitagawa 2002). In pharmaceutical industry, they are widely used as raw materials for the production of steroid hormones (Guclu Ustundag and Mazza 2007). Steroidal saponin from Anemarrhena asphodeloides, i.e., timosaponin AIII was found to inhibit the growth of tumor cells and can be considered as a significant compound for the development of the novel anticancerous drug (Wang et al. 2016a, b). Steroidal saponin diosgenin increases bone formation (Folwarczna et al. 2016), executes anti-thrombotic activity by inhibiting the activity of factor VIII and platelet aggregation (Zhang et al. 2013a, b, c), cardioprotective (Jayachandran et al. 2016), suppresses skin inflammation (Kim et al. 2016), have potential to treat liver fibrosis (Xie et al. 2015), useful in the treatment of metabolic disease by regulating cholesterol homeostasis, effective in reversing hyperlipidemia (Fuller and Stephens 2015), anti-inflammatory, improves antioxidant status, inhibits lipid peroxidation (Chen et al. 2015) etc. So this compound can be further used for pharmacotherapy of various diseases.

Spicatoside A from Liriope platyphylla possesses anti-inflammatory activities, anti-asthma activities, anti-osteoclastogenesis activities, memory consolidation activities, neurite outgrowth activities, anti-cancer activities (Ramalingam and Kim 2016) while steroidal saponin from allium species possesses antispasmodic effect, cardioprotective activity, antifungal activity and cytotoxic activity (Sobolewska et al. 2016).

The antiproliferative and cytotoxic activity of steroidal saponins were mainly explored by researchers. It was observed that Paris polyphylla steroidal saponins (PPSS) induce apoptosis and autophagy in human lung cancer cell lines that indicate the anti-cancerous properties of steroidal saponins (He et al. 2015). Additionally, spirostane-type steroidal glycosides from Allium flavum also showed cytotoxicity against a human cancerous cell line (Rezgui et al. 2014). Trillium tschonoskii steroidal saponins have a potential of prevention and treatment of colorectal cancer (Li et al. 2015a, b, c) and they also have the capability to reverse the multidrug resistance and enhance the drug sensitivity in hepatocellular carcinoma (Wang et al. 2013). Steroidal saponin TTB2 from Trillium tschonoskii exerts anticancer effects against Ewing sarcoma cell line through cell cycle arrest at G2/M and S phase (Huang and Zou 2015). Terrestrosin D, PSVII and diosgenin induce apoptosis in prostate, cervical and breast cancer stem cells, respectively (Zhang et al. 2014a, b; Bhuvanalakshmi et al. 2017). Polyphyllin Ι from Paris polyphylla induces cell cycle arrest and ROS dependent autophagy in colorectal cancerous cells.

Anticarcinogenic activity was shown by a variety of steroidal saponins from different plants including Digitalis trojana (Kirmizibekmez et al. 2014), Allium schoenoprasum (Timité et al. 2013), Dioscorea zingiberensis (Tong et al. 2012), Fagonia indica (Waheed et al. 2012), Rhizoma Paridis (Xiao et al. 2012), Solanum violaceum (Yen et al. 2012), Agave sisalana (Chen et al. 2011a, b), Anemarrhena asphodeloides (Kang et al. 2011), Dioscorea bulbifera (Liu et al. 2011), Trigonella foenum-graecum (Kawabata et al. 2011), Paris polyphylla (Zhu et al. 2011), Raphia farinifera (Tapondjou et al. 2015) etc.

Characterized enzymes involved in the biosynthesis of steroidal saponins

Both the cytosolic mevalonate (MVA) pathway and plastidial methylerythritol 4-phosphate (MEP) pathway are involved in the biosynthesis of steroidal saponins. Acetyl Co-A is the precursor of MVA pathway in the cytosol while in the chloroplast, glyceraldehyde-3-phosphate and pyruvate serve as precursor molecules to initiate MEP pathway. Both pathways lead to the formation of dimethylallyl diphosphate (DMAPP) that is used to synthesize squalene via the sequential action of three enzymes, i.e., geranyl diphosphate synthase (GPS), farnesyl diphosphate synthase (FPS) and squalene synthase (SQS). Squalene is then converted into 2, 3-oxidosqualene under the catalysis of squalene epoxidase (SE). The cyclization of 2, 3-oxidosqualene is then carried out by different oxidosqualene cyclases leading to the products that undergo cyclization, hydroxylation and glycosylation reactions ultimately yielding different types of steroidal saponin glycosides.

Some of the enzymes related to saponin biosynthesis have been characterized and most are yet to be characterized. The exact biosynthetic pathway of saponin biosynthesis is not yet established and now it has become an interesting area of research to find out each enzyme of this biosynthetic pathway and signaling molecules involved in the regulation of saponin biosynthesis. Some characterized enzyme of this pathway in different plant species is reviewed and summarized below.

Enzymes of MVA pathway

Enzymes of MVA pathway was characterized in different plants as 3-hydroxy-3-methylglutaryl CoA reductase (HMGR) is the crucial regulatory and rate-limiting enzyme of mevalonate pathway of saponin biosynthesis that catalyzes the irreversible conversion of HMGR to mevalonate. In addition to steroidal saponin, HMGR is also involved in the biosynthesis of phytosterols and sitosterols. By increasing HMGR gene expression, diosgenin content significantly increased in in vitro cultures of Dioscorea zingiberensis (Diarra et al. 2013). Similarly in Medicago truncatula, silencing of Mkb1 (E3 ubiquitin ligase), that control the activity of HMGR results in accumulation of monoglycosylated saponins (Moses et al. 2014a, b). This enzyme was characterized in different plants including Hevea brasiliensis (Chye et al. 1991), potato (Bhattacharyya et al. 1995), wheat (Aoyagi et al. 1993), Camptotheca acuminate (Maldonado-Mendoza et al. 1997), mulberry (Jain et al. 2000), rice (Ha et al. 2001), Capsicum annuum (Ha et al. 2003), Ginkgo biloba (Shen et al. 2006), Corylus avellana (Wang et al. 2007), Euphorbia pekinensi (Cao et al. 2010), Salvia miltiorrhiza (Dai et al. 2011), coffee (Tiski et al. 2011), Glycyrrhiza uralensis (Rong et al. 2011), Withania somnifera (Akhtar et al. 2013), Dendrobium officinale (Zhang et al. 2014a, b), Paris fargesii (Liang et al. 2014), Centella asiatica (Kalita et al. 2015), Arabidopsis (Suzuki et al. 2004), Cyanotis arachnoidea (Wang et al. 2014a, b, c) and Panax ginseng (Kim et al. 2014).

Mevalonate kinase (MK) catalyzes a step in the isoprenoid biosynthetic pathway, which ultimately leads to huge number of compounds that play important roles in plant growth and development (Tang and Newton 2006). This enzyme was characterized in Catharanthus roseus (Schulte et al. 2000) and Bacopa monniera (Kumari et al. 2015). Mevalonate diphosphate decarboxylase enzyme requires ATP and Mg+2 to convert mevalonate 5-diphosphate (MVAPP) into isopentenyl diphosphate (IPP), has been characterized in Bacopa monniera (Abbassi et al. 2015). Isopentenyl diphosphate isomerase (IPP isomerase) is an important enzyme of isoprenoid biosynthesis that converts IPP into DMAPP has been characterized in Tripterygium wilfordii (Tong et al. 2015), Taxus media (Shen et al. 2015) and Camptotheca acuminate (Pan et al. 2008).

Another important enzyme of isoprenoid biosynthesis is FPS that forms farnesyl diphosphate by a head to tail condensation of two molecules of IPP and one molecule of DMAPP (Fig. 2a). FPS can increase terpenoid accumulation in plants as suggested by gene expression analysis (Zhao et al. 2015). Gene expression studies have demonstrated that FPS expression is positively related to the isoprene content in plants. This gene has been characterized in many plants including Bacopa monniera (Vishwakarma et al. 2012), Tripterygium wilfordii (Zhao et al. 2015) and Arabidopsis thaliana (Keim et al. 2012).
Fig. 2

Steroidal saponin biosynthetic pathway: a overview of steroidal saponin biosynthesis in plants that involve both cytosolic mevalonate (MVA) and plastidial methylerythritol 4-phosphate (MEP) pathways. b This figure mainly represents known P450 s, UGTs and glucosidases involved in hydroxylation, oxidation, glycosylation and final cyclization of saponin backbone. Enzyme and species names are italicized. Dashed arrows imply multiple steps in the pathway. DHCR24 delta 24-sterol reductase, DHCR7 7-dehydrocholesterol reductase, CyP51 sterol 14α-demethylase

Enzymes of methylerythritol 4-phosphate (MEP) pathway

Enzymes of MEP pathway was also characterized in different plants like 1-deoxy-d-xylulose 5-phosphate synthase (DXS) enzyme that was the first enzyme of MEP pathway in plastid that catalyzes the formation of 1-deoxy-d-xylulose 5-phosphate (DXP) by condensation of C1 aldehyde group of d-glyceraldehyde 3-phosphate (GAP) and pyruvate. Intramolecular rearrangement and reduction of DXP were catalyzed by DXP reductoisomerase (DXR) that results in the formation of 2-C-methyl-d-erythritol 4-phosphate (MEP). MEP is further converted into 2C-methyl-d-erythritol 2, 4-cyclodiphosphate (MEC) by the activity of MEC synthase enzyme. DXS was characterized in Aquilaria sinensis (Xu et al. 2014), Maize (Cordoba et al. 2011), DXR enzyme was characterized in Ginkgo biloba (Gong et al. 2005), 2C-methyl-d-erythritol 2,4-cyclodiphosphate (MEC) synthase enzyme of MEP pathway was characterized in Taxus media (Jin et al. 2006) and Ginkgo biloba (Kim et al. 2006). In the last step of MEP pathway both IPP and DMAPP is formed and they also interconvertible in another form or isomerized by the activity of IPP isomerase (Fig. 2a). IPP isomerase was characterized in Taxus media (Shen et al. 2015), Tripterygium wilfordii (Tong et al. 2016), Gossypium barbadense (Wang et al. 2009a, b), Arabidopsis thaliana (Phillips et al. 2008), Camptotheca acuminate (Pan et al. 2008), Cinchona robusta (Ramos-Valdivia et al. 1997) etc.

Both phytosterol and saponins are synthesized from the same precursors that are squalene and 2, 3-oxidosqualene (Haralampidis et al. 2002). SQS is a membrane-bound enzyme that catalyzes the initial enzymatic reaction in the biosynthesis of triterpenoids like plant sterols from MVA isoprenoid pathway (Abe et al. 1993). It catalyzes the condensation of two FPP molecules into squalene. SQS was characterized in a wide variety of plant species including Panax ginseng (Kim et al. 2011), Chlorophytum borivilianum (Kalra et al. 2013), Ornithogalum caudatum (Liu et al. 2017), Panax notoginseng (Jiang et al. 2017), Siraitia grosvenorii (Zhao et al. 2017), Salvia miltiorrhiza (Rong et al. 2016) and Magnolia officinalis (Zha et al. 2016).

SE is another rate-limiting enzyme that catalyzes the epoxidation of the double bond of squalene to produce 2,3 oxidosqualene in saponin biosynthesis. This is the first oxidation step in phytosterol and saponin biosynthesis in plants. It was shown that the expression of SE in Eleutherococcus senticosus was affected by endophytic fungi (Xing et al. 2012). SE is one of the important enzymes for biosynthesis of saponins in vitro using synthetic biology approach. Major work related to this enzyme was performed in Panax species that is supposed to be an important source of triterpenoidal saponin. Molecular cloning, expression profiling and characterization of SE were done in Panax notoginseng and it was observed that it is highly expressed in root tissues. Methyl jasmonate (MeJA) treatment increases the expression level of SE in Panax ginseng (Choi et al. 2005). Chitosan induces saponin biosynthesis by increasing the expression level of squalene epoxidase, but it was found that the activity of chitosan and the expression level of SE were inhibited by chitosan inhibitor PD98059.

Two isoforms of SE were identified in Panax ginseng, one is involved in ginsenoside biosynthesis and another one is involved in phytosterol synthesis (Han et al. 2010). Besides Panax species and yeast, SE was also characterized in Euphorbia tirucalli (Uchida et al. 2007), Withania somnifera (Razdan et al. 2013), Arabidopsis (Laranjeira et al. 2015), Gynostemma pentaphyllum (Guo et al. 2016) etc.

Cycloartenol synthase (CAS) is another membrane-bound enzyme as SQS and SE that is involved in phytosterol biosynthesis in a plant system. In arabidopsis, CAS1 is reported to be involved in the biogenesis of plastid (Babiychuk et al. 2008). CAS was also characterized in Withania somnifera (Dhar et al. 2014), Nicotiana (Gas-Pascual et al. 2014), Siraitia grosvenorii (Zhao et al. 2017) etc. In addition to the above-mentioned enzymes, many P450 and glucosyltransferases that were involved in the biosynthesis of steroidal saponin is discussed below.

Later step modification enzymes (P450 and UGT)

Intermediates of the phytosterol pathway are involved in saponin biosynthesis and primarily enzymes that belong to the multigene families of oxidosqualene cyclases (OSCs), P450 s and family 1 of UGTs are supposed to be involved in saponin biosynthesis (Augustin et al. 2011). Both P450s and UGTs are the member of plant supergene families. In plants, during the biosynthesis of diverse plant secondary metabolites like, terpenoids, fatty acids, lignins, hormones, sterols, pigments and defense-related phytoalexins, P450s catalyzes the oxidative reactions (Schuler 1996). P450s and UGTs are considered as a key enzyme, which leads to diversification of natural products in plants. The diverse characteristics of these enzymes make their identification in saponin pathway difficult. Arabidopsis thaliana contains around 246 P450 genes, and it is really difficult to analyze the function of each P450 gene using reverse genetics approach (Nelson 2006). Since these modifications are necessary for making the saponins soluble and active. Researchers are making large-scale experiments and attempts to isolate P450 s and UGTs involved in saponin biosynthetic pathway in plants.

Plant P450 can be divided into two groups that are mainly A-type and non A-type P450. A-type P450 are mainly involved in secondary metabolites biosynthesis while non A-type P450 is a highly diverse group that includes P450 related to lipid or hormone metabolism (Paquette et al. 2000). Animal, microbial and plant P450 differ at their protein level and show sequence homology of 30% or less than 30%. Beside this CyP51 family members are the most conserved P450 among phyla and share sequence homology more than 30–40% (Bak et al. 2011). In the eukaryotic system, members of CyP51 family catalyze 14α-demethylation of sterols.

As reported earlier that cycloartenol is an important intermediate between 2,3 oxidosqualene and obtusifoliol in photosynthetic eukaryotic organisms while in non-photosynthetic eukaryotic organism cycloartenol is not present and lanosterol is derived directly from oxidosqualene (Fabris et al. 2014). Obtusifoliol 14α demethylase gene was characterized from Sorghum bicolor (L.) and showed strict substrate specificity towards obtusifoliol, which belongs to P450 gene family CyP51 (Bak et al. 1997). Wheat sterol 14α demethylase gene (CyP51) was found to complement ERG11 (lanosterol 14-alpha-demethylase) disrupted engineered yeast strain (Cabello-Hurtado et al. 1999). Steroidal saponins are mainly synthesized from cholesterol by oxygenations at C-16, C-22 and C-26 positions (Ohnishi et al. 2009). P450s that were identified in a transcriptome analysis of medicinal plants and supposed to be involved in steroidal saponin biosynthesis is summarized in Fig. 2b.

Glycosylation of saponins is supposed to be the last step in the biosynthesis of saponins. Glycosylation also regulates the biological activities and solubility of these naturally derived saponins (Sawai and Saito 2011). The identification and characterization of these glycosyltransferase enzymes that catalyze the transfer of sugar moiety to these steroidal and terpenoidal backbones will certainly help us to understand the mechanism of the diversity of these saponins and also control their biological activities in plants. Despite of their importance only few glucosyltransferases are identified and characterized. We have compiled some of the recently identified and characterized UGTs along with their function (Fig. 2b).

Presence and absence of sugar residue at specific position allow saponin glycoside to achieve their different biological activity. For example presence of C-26 sugar in avenacosides A and B from oat plant inhibited their antimicrobial activity but the removal of sugar residue from same carbon position required to gain antimicrobial activity in this plant (Osbourn 1996). Similarly, 26 desgluco derivatives of tobacco furostanol saponin B is required to maintain its hemolytic and antifungal activity while its structural homolog had no such kind of activity (Gruenweller et al. 1990). Number and position of sugar moiety attached with saponin molecule also influence its biological activity as incorporation of α-l-rhamnosyl at C-2 of the glucosyl unit of diosgenin leads to a disaccharide saponin with potent cytotoxicity but when l-rhamnose is attached to C-3 or C-4 of d-glucose, the resulting diosgenyl saponins do not exhibit significant cytotoxic activity against HL-60 cells (Perez-Labrada et al. 2012).

Biosynthesis of steroidal saponin can be best studied in solanum species. Wide ranges of steroidal saponins are synthesized in this genus. It was reported that SaGT4A glucosylate steroidal saponins as well as steroidal alkaloids in Solanum aculeatissimum (Kohara et al. 2005) while StSGT a glycosyltransferase from Solanum tuberosum share 75% sequence homology with SaGT4A only glycosylate steroidal alkaloids (Moehs et al. 1997). It was reported that fructose was added to furostan saponins at the position of C6-OH of 26-O-β-d-glucopyranosyl by β-fructosidase enzyme of a microbial strain of Arthrobacter nitroguajacolicus. This kind of fructosylation is possible only with furostan saponins but not with spirostan saponins due to the stereo-hindrance effect (Liu et al. 2015a, b).

Generally, spirostanol saponins are water-insoluble but the attachment of α-l-rhamnopyranosyl group with the glucopyranosyl moiety at the C2-OH of the C3-O-glycoside; increase the solubility of saponin as well as its absorption by the human body. Toruzyme 3.0 L, a kind of cyclodextrin glucanotransferase was used to synthesize steroidal saponins with novel sugar chains to increase their solubility as well as their activity. Nine steroidal saponins with different aglycones and sugar chains were used as substrates to be glucosylated by this cyclodextrin glucanotransferase (Wang et al. 2010). Cantalasaponin I, a spirostanoside from Agave sisalanta was used as substrates to be glucosylated by toruzyme 3.0 L (CGT), and five new glucosylated products were isolated and identified (Kang et al. 2012a, b, c). Beside glycosylation, deglycosylation of steroidal saponin to sapogenin was reported to be carried out by rumen bacteria, especially the cell-associated enzymes fraction of ruminal content (Wang and McAllister 2010). UGTs, as well as glucosidases that were identified in a transcriptome analysis of steroidal saponin-producing plants, were summarized in Fig. 2b.

Newly identified steroidal saponins in last decade

Generally, steroidal saponins were reported in monocot families like Dioscoreaceae, Amaryllidaceae, Smilacaceae, Liliaceae, Agavaceae, Alliaceae, Asparagaceae, Bromeliaceae, Palmae and Scrophulariaceae, etc, and they are accumulated abundantly in crop plants such as yam, alliums, asparagus, fenugreek, yucca and ginseng (Hostettmann and Marston 2005). The presence of steroidal saponin was also reported in certain dicot families like Apocynaceae, Leguminosae, Solanaceae etc. (Moses et al. 2014a, b). Steroidal saponins from different angiosperms were extracted and their structure was elucidated by spectral analysis. Modern spectrometric methods used for the structural analysis of saponins are mass spectrometry (MS), nuclear magnetic resonancy (NMR) and IR. In different organs of the plant there is a considerable variation in the quantity of saponin. Saponin content depends on age, cultivar and geographical distribution of plant (Vincken et al. 2007). Most commonly steroidal saponins are isolated from underground parts of the plant especially roots and rhizomes, and less often from above ground tissues such as leaves, stems, seeds, and fruits (Challinor and De Voss 2013). Cereals and grasses are generally deficient in saponins, with some notable exceptions such as avena species (oats), which accumulate both triterpenoid and steroidal saponins (Osbourn 2003). It is known that over 90 plant families contain steroidal saponins and many new occurrences are still being reported (Hostettmann and Marston 1995). Some recently identified steroidal saponin with their plant part is summarized in Table 1.
Table 1

List of some recently identified, steroidal saponin-producing plants

S. No.

Steroidal saponin

Plant

Plant part

References

1.

Sarsasapogenin M, Sarsasapogenin N

Asparagus officinalis

Roots

Huang and Kong (2006)

2.

Ornithosaponins A–D

Ornithogalum thyrsoides

Bulbs

Kuroda et al. (2006)

3.

Three spirostanol and one furostanol saponin

Calamus insignis

Stem

Ohtsuki et al. (2006)

4.

Chekiangensosides A and B

Cynanchum chekiangense

Roots

Li et al. (2006)

5.

Neosibiricosides A–D

Polygonatum sibiricum

Rhizomes

Ahn et al. (2006)

6.

Two furostane type, two cholestane and two spirostane type

Tribulus alatus Del

Aerial parts

Temraz et al. (2006)

7.

Spirostane type steroidal saponin

Agave shrevei

leaves

Pereira et al. (2004)

8.

Two steroidal saponins

Allium ursinum L

Underground parts

Sobolewska et al. (2006)

9.

Two steroidal saponins

Capsicum frutescens

Whole Plant

De Lucca et al. (2006)

10.

Timosaponins AI, AII, AIII, and AIV, and timosaponins BI, and BII

Anemarrhena asphodeloides

Rhizome

Nian et al. (2006)

11.

Three steroidal glycosides

Furcraea selloa

Leaves

El-Sayed et al. (2006)

12.

Diosgenin

Solanum lyratum

Whole plant

Sun et al. (2006)

13.

Two new spirostanol saponins

Smilax medica

Roots

Sautour et al. (2006)

14.

Racemosides A, B and C

Asparagus racemosus

Fruits

Mandal et al. (2006)

15.

Atropurosides A–G

Smilacina atropurpurea

Rhizomes

Zhang et al. (2006)

16.

Taccaoside C and D

Tacca plantaginea

Whole plant

Liu et al. (2006)

17.

Timosaponin N, E1, E2, O and Purpureagitosid

Anemarrhena asphodeloides

Rhizomes

Kang et al. (2006)

18.

Ophiopogonin E

Ophiopogon japonicus

Tubers

Cheng et al. (2006)

19.

Solanigrosides C–H

Solanum nigrum

Whole plant

Zhou et al. (2006)

20.

A pair of diastereoisomeric steroidal saponins

Tupistra chinensis

Rhizomes

Zou et al. (2006)

21.

Steroidal saponins 1, 2, 3 and 4

Smilax china

Whole Plant

Shao et al. (2007)

22.

Ypsilandroside A, B, isoypsilandroside A,B and isoypsilandrogenin

Ypsilandra thibetica

Whole plant

Xie et al. (2006)

23.

Polypunctosides A–D

Polygonatum punctatum

Rhizomes

Yang and Yang (2006)

24.

Dioscin, protodioscin and protogracillin

Dioscorea septemloba Thunb

Rhizomes

Tan et al. (2006)

25.

Turrillianoside

Veronica turrilliana

Aerial parts

Kostadinova et al. (2007)

26.

Six new steroidal saponins

Asparagus acutifolius

Roots

Sautour et al. (2007)

27.

Yuccalan

Yucca smalliana

Leaves

Jin et al. (2007)

28.

Cynanversicoside A, B, D, G, glaucoside C and glaucogenin C-3-O-beta-d-thevetopyranoside

Radix Cynanchi Atrati

Whole plant

Liang et al. (2007)

29.

Two new steroidal saponins

Dracaena ombet

Leaves

Moharram and EI-Shenawy (2007)

30.

Filiasparosides A–D

Asparagus filicinus

Roots

Zhou et al. (2007)

31.

A pair of stereoisomeric spirostanol saponins and a new cholestane saponin

Paris polyphylla

Rhizome

Zhao et al. (2007)

32.

Elephanoside A, elephanosides B–F, Ys-II, Ys-IV

Yucca elephantipes

Stems

Zhang et al. (2008)

33.

Pseudoprotodioscin, methyl protodioscin and dioscin

Dioscorea nipponica Makino

Rhizome

Lin et al. (2007)

34.

Methyl parvifloside, methyl protodeltonin, zingiberensis saponin I, deltonin

Dioscorea villosa

Roots

Hayes et al. (2007)

35.

Paridiformoside B

Lysimachia Paridiformis

Whole plant

Xu et al. (2007a, b)

36.

Shatavarins VI–X

Asparagus racemosus

Roots

Hayes et al. (2008)

37.

Aspafiliosides E and F

Asparagus filicinus

Roots

Zhou and Chen (2008)

38.

Balanitin-6 and balanitin-7

Balanites aegyptiaca

Kernels

Gnoula et al. (2008)

39.

Ilwensisaponin A and C

Verbascum pterocalycinum var. mutense

Flowers

Akkol et al. (2007)

40.

Zingiberenin G

Dioscorea zingiberensis

Rhizomes

Xu et al. (2007a, 2007b)

41.

Lyconosides Ia, Ib, II, III, and IV

Solanum lycocarpum St. Hil.

Fruits

Nakamura et al. (2008)

42.

Five steroidal saponins

Allium leucanthum C. Koch

Flower

Mskhiladze et al. (2008a, b)

43.

Cesdiurins I–III

Cestrum diurnum L

Leaves

Fouad et al. (2008)

44.

Ophiofurospiside A

Ophiopogon japonicus (Thunb.) Ker-Gawl

Tubers

Xu et al. (2008)

45.

Mannioside A

Dracaena mannii

Stem bark

Tapondjou et al. (2008)

46.

Six C-21 steroidal glycosides

Cynanchum auriculatum Royle ex Wight

Root tuber

Peng et al. (2008)

47.

Paris saponin I, Paris saponin V, Paris saponin VI, Paris saponin VII, Paris saponin H

Paris polyphylla Smith var stenophylla Franch

Whole plant

Yin et al. (2008)

48.

Stemucronatoside K

Stephanotis mucronata

Whole plant

Ye et al. (2008)

49.

Three new spirostanol glycosides, a new furostanol glycoside, and a new cholestane glycoside

Clintonia udensis

Rhizomes

Matsuo et al. (2008)

50.

Three steroidal saponins

Paris polyphylla Smith

Rhizomes

Deng et al. (2008)

51.

Two new steroidal saponin along with curillin G, asparagoside E, asparoside A, asparoside B

Smilax aspera subsp. mauritanica

Roots

Belhouchet et al. (2008)

52.

Smilacinoside A, B, C, D and funkioside D, aspidistrin

Smilacina atropurpurea

Dried tender aerial parts

Yang et al. (2009)

53.

Solanolactosides A, B, Torvosides M, N

Solanum torvum

Aerial parts

Lu et al. (2009)

54.

Two new steroidal saponins

Tribulus terrestris

Fruits

Su et al. (2009)

55.

Polygonoides A and B

Polygonatum sibiricum

Rhizome

Xu et al. (2009a, b, c)

56.

Five new steroidal saponins

Tribulus terrestris

Fruits

Su et al. (2009)

57.

Eleven steroidal saponins

Trillium erectum

Roots

Hayes et al. (2009)

58.

Two new furostanol saponins and one new spirostanol saponin

Paris polyphylla

Rhizome

Zhao et al. (2009)

59.

Seven spirostanol type saponins

Allium leucanthum

Flowers

Mskhiladze et al. (2008a, 2008b)

60.

Two new steroidal saponins

Allium macrostemon bunge

Dried bulbs

Chen et al. (2009)

61.

Chloragin

Chlorophytum nimonii (Grah) Dalz

Aerial part

Lakshmi et al. (2009)

62.

Three steroidal saponins

Polygonatum odoratum

Rhizomes

Wang et al. (2009a, 2009b)

63.

Three new furostanol saponins together with known protodioscin, pseudoprotodioscin and dioscin

Smilax excelsa

Rhizomes

Ivanova et al. (2009)

64.

15-hydroxy-pseudoprotodioscin and 15-methoxy-pseudoprotodioscin

Smilax china

Tubes

Huang et al. (2009)

65.

Padelaosides A and B

Paris delavayi

Rhizomes

Zhang et al. (2009a, b)

66.

Ceparosides C and D

Allium cepa L

Seeds

Yuan et al. (2009)

67.

Five spirostanol saponins, Three furostanol saponins

Agave utahensis

Whole plant

Yokosuka and Mimaki (2009)

68.

Zingiberenin F

Dioscorea zingiberensis

Rhizome

Xu et al. (2009a, 2009b, 2009c)

69.

Ypsilandrosides C–G

Ypsilandra thibetica

Whole plant

Xie et al. (2009)

70.

Eight new spirostanol saponins and three new furostanol saponins

Agave utahensis

Whole plants

Yokosuka et al. (2009)

71.

Shatavaroside A and shatavaroside B together with filiasparoside C

Asparagus racemosus

Roots

Sharma et al. (2009)

72.

Yamogenin II

Asparagus officinalis L

Dried Stems

Sun et al. (2010)

73.

Spirostanol saponin, chantrieroside A

Tacca chantrieri

Rhizomes

Zhang et al. (2009a, b)

74.

Three new steroidal saponins

Tribulus terrestris L

Fruits

Liu et al. (2010a, b)

75.

Two new steroidal saponins

Tribulus terrestris L

Fruits

Liu et al. (2010a, 2010b)

76.

Two steroidal saponin

Hosta sieboldiana

Leaf and Leafstalk

Yada et al. (2010)

77.

Monodesmosidic spirostanol saponi

Agave macroacantha Zucc

Leaves

Eskander et al. (2010)

78.

Orchidastrosides A–F, and chloromaloside D

Chlorophytum orchidastrum

Roots

Acharya et al. (2010)

79.

Timosaponins AIII, BIII, and D

Anemarrhena asphodeloides

Rhizome

Lee et al. (2010)

80.

Tribufurosides D and E

Tribulus terrestris L

Fruits

Xu et al. (2009a, 2009b, 2009c)

81.

Three new steroid saponin

Tacca integrifolia

Rhizome

Shwe et al. (2010)

82.

Parvifloside, protodeltonin, protodioscin, protogracillin, zingiberensis saponin, deltonin, dioscin and trillin

Dioscorea zingiberensis C.H. Wright

Rhizome

Li et al. (2010)

83.

Two new furostanol saponins

Lilium longiflorum Thunb

Bulbs

Munafo et al. (2010)

84.

Angudracanosides A–F

Dracaena angustifolia

Fresh stems

Xu et al. (2010)

85.

Esculeoside A

Solanum lycopersicum

Ripe Fruit

Nohara et al. (2010)

86.

Filiasparosides E, F, filiasparoside G, asparagusin A filiasparoside A, filiasparoside B, aspafilioside A, aspafilioside B, and filiasparoside C

Asparagus filicinus

Roots

Wu et al. (2010)

87.

Fistulosaponins A–F

Allium fistulosum

Seeds

Lai et al. (2010)

88.

Deistelianosides A, B and arboreasaponins A and B

Dracaena deisteliana and Dracaena arborea

Stem and bark

Kougan et al. (2010)

89.

Ypsilandrosides H–L and a known saponin polyphylloside III

Ypsilandra thibetica

Whole plant

Lu et al. (2010)

90.

Two furostanol saponins

Ruscus ponticus

Leaves

Napolitano et al. (2010)

91.

Two steroidal saponins

Solanum surattense Burm. f.

Aerial parts

Lu et al. (2011)

92.

Two new steroidal saponins

Agave sisalana

Leaves

Chen et al. (2011a, 2011b)

93.

Diosbulbisides D and E

Dioscorea bulbifera

Rhizomes

Liu et al. (2011)

94.

Lirigramosides A (1) and B

Liriope graminifolia (Linn.)

Underground parts

Wang et al. (2011a, b)

95.

Five steroidal glycosides, including three spirostane, one furostane and one cholestane type saponins

Yucca gloriosa L

Rhizomes

Skhirtladze et al. (2011)

96.

Helosides A and B

Chamaelirium luteum

Roots

Challinor et al. (2011)

97.

A new steroidal saponin

Ophiopogon japonicus

Dried roots

Qu et al. (2011)

98.

Polyphyllin D

Paris polyphylla

Rhizome

Chan et al. (2011)

99.

Thirteen steroidal saponins

Beaucarnea recurvata

Leaves

Eskander et al. (2011)

100.

Esculeoside B-5

Solanum lycopersicum

Ripe fruit

Ohno et al. (2011)

101.

DT-13

Liriope muscari (Decne.) Baily

Tuber

Ma et al. (2011)

102.

A bidesmosidic steroidal saponins

Yucca schidigera

Bark

Kowalczyk et al. (2011)

103.

A new aglycone of amplexicogenin B

Cynanchum amplexicaule

Whole plant

Chen et al. (2011a, 2011b)

104.

Pallidiflosides A, B and C

Fritillaria pallidiflora

Dry bulbs

Shen et al. (2011)

105.

Desmettianosides A and B

Yucca desmettiana

Leaves

Diab et al. (2012)

106.

Parvifloside, methyl protodeltonin, trigofoenoside A-1, zingiberensis saponin I, deltonin, dioscin and prosapogenin A of dioscin

Dioscorea villosa

Rhizome

Yoon et al. (2012)

107.

Seven spirostane and furostane-type glycosides

Cestrum ruizteranianum

Fruits

Galarraga et al. (2011)

108.

Timosaponin J, timosaponin K, (25S)-karatavioside C, timosaponin L, and (25S)-officinalisnin-I

Anemarrhena asphodeloides

Rhizome

Kang et al. (2012a, 2012b, 2012c)

109.

Two new furostanol saponins sarsaparilloside B and sarsaparilloside C

Smilax ornata Lem.

Roots

Challinor et al. (2012a, 2012b, 2012c)

110.

A new steroidal saponin

Allium ampeloprasum

Bulbs

Adão et al. (2012)

111.

Lycioside A and lycioside B

Lycium barbarum

Seeds

Wang et al. (2011a, 2011b)

112.

Parisyunnanosides G–I, one new C(21) steroidal glycoside, parisyunnanoside J

Paris polyphylla

Rhizome

Kang et al. (2012a, 2012b, 2012c)

113.

Two new C-21 steroidal glycosides

Cynanchum amplexicaule

Whole plant

Chen et al. (2012)

114.

Dioscins E and F

Dioscorea nipponica

Rhizomes

Zhang et al. (2012a, b)

115.

Ophiopogonins H–O

Ophiopogon japonicus

Tuber

Zhang et al. (2012a, 2012b)

116.

Japonicoside A, japonicoside B and japonicoside C

Smilacina japonica

Dried rhizomes and roots

Liu et al. (2012a, b)

117.

Pallidifloside D, pallidifloside E, pallidifloside G, pallidifloside H and pallidifloside I

Fritillaria pallidiflora Schrenk

Dry bulbs

Shen et al. (2012)

118.

Tupisteroide A–C

Tupistra chinensis

Roots

Liu et al. (2012a, 2012b)

119.

Two new steroidal saponins

Tribulus terrestris

Fruits

Chen et al. (2013)

120.

Pariposides A–D

Paris polyphylla var. yunnanensis

Roots

Wu et al. (2012a, b)

121.

15 steroidal saponins

Chamaelirium luteum (false unicorn)

Roots

Challinor et al. (2012a, 2012b, 2012c)

122.

Chonglouosides SL-1-SL-6

Paris polyphylla

Stems and Leaves

Qin et al. (2012)

123.

A novel steroidal saponin

Fagonia indica

Aerial Parts

Waheed et al. (2012)

124.

Eleven steroidal saponins

Paris polyphylla

Rhizomes

Wu et al. (2012a, 2012b)

125.

Two new furostanol saponins 1 and 2

Ruscus aculeatus L

Underground parts

De Marino et al. (2012)

126.

Stauntosides C–K

Cynanchum stauntonii

Roots

Yu et al. (2013)

127.

Ophiopogonin P–S

Ophiopogon japonicus

Tuberous roots

Li et al. (2013)

128.

Two new steroidal saponins

Smilax microphylla

Roots and Rhizome

Lin et al. (2012)

129.

A new isospirostanol-type steroidal saponin

Smilax scobinicaulis

Roots and Rhizome

Zhang et al. (2013a, 2013b, 2013c)

130.

Shatavaroside C

Asparagus racemosus

Roots

Sharma et al. (2012)

131.

Avenacosides A and B

Avena sativa L

Grains

Pecio et al. (2012)

132.

Seven new steroidal saponins

Lilium brownii var. viridulum

Bulbs

Hong et al. (2012)

133.

Tupichinin A

Tupistra chinensis

Rhizomes

Pan et al. (2012)

134.

Pumilum A

Lilium pumilum DC

Bulbs

Zhou et al. (2012)

135.

Three new steroidal saponins

Dracaena marginata

Bark

Rezgui et al. (2013)

136.

Nolinospiroside F

Ophiopogon japonicus

Roots

Sun et al. (2013)

137.

Three new steroidal compounds

Hosta longipes

Leaves

Kim et al. (2013)

138.

Four spirostane-type glycosides

Allium schoenoprasum

Whole plant

Timité et al. (2013)

139.

Seven steroidal glycosides

Solanum torvum

Fruits

Colmenares et al. (2013)

140.

Torvpregnanosides A and B, two pregnane glycosides, and torvoside Q, a 23-keto-spirostanol glycoside

Solanum torvum

Aerial parts

Lee et al. (2013)

141.

Solanolactoside C

Solanum torvum Swartz

Aerial part

Shu et al. (2013)

142.

Anemarnoside A and anemarnoside B

Anemarrhena asphodeloides

Whole plant

Liu et al. (2013)

143.

Three furostanol type saponins

Digitalis trojana

Aerial parts

Kirmizibekmez et al. (2014)

144.

Two new furostanol saponins

Ophiopogon japonicus

Tubers

Guo et al. (2013)

145.

Two new steroidal saponins

Selaginella uncinata (Desv.)

Whole plant

Zheng et al. (2013)

146.

Magueyosides A–E

Agave offoyana

Flowers

Pérez et al. (2013)

147.

Three novel cholestane-type steroidal glycosides and two novel spirostane-type steroidal saponins

Polygonatum odoratum

Rhizome

Bai et al. (2014)

148.

Three new steroidal saponins

Ophiopogon japonicus (Thunb.) Ker-Gawl

Tubers

Ye et al. (2013)

149.

Dioscoreanosides A–K

Dioscorea bulbifera var. sativa

Flowers

Tapondjou et al. (2013)

150.

Drangustosides A–B

Dracaena angustifolia Roxb

Whole plant

Huang et al. (2013)

151.

Longipetalosides A–C

Tribulus longipetalus

Whole plant

Naveed et al. (2014)

152.

Cambodianosides A–F

Dracaena cambodiana

Whole plant

Shen et al. (2014)

153.

Five oleanane-type saponins

Ganophyllum giganteum

Root bark

Montes et al. (2014)

154.

Three new spirostane-type glycosides

Allium flavum

Whole plant

Rezgui et al. (2014)

155.

Five steroidal saponins

Agave offoyana

Leaves

Pérez et al. (2014)

156.

Diospreussinosides A–C

Dioscorea preussii

Rhizomes

Tabopda et al. (2014)

157.

Riparoside B and timosaponin J

Smilax riparia

Roots and Rhizomes

Wu et al. (2014a, b)

158.

Zingiberenosides A and B

Dioscorea zingiberensis

Rhizomes

Zheng et al. (2014)

159.

Two new furostanol saponins

Asparagus cochinchinensis

Roots

Zhu et al. (2014)

160.

Cynanosides A–O

Cynanchum atratum

Roots

Yan et al. (2014)

161.

Diospreussinosides A–C

Dioscorea preussii

Rhizomes

Tabopda et al. (2014)

162.

Six pennogenyl saponins

Paris quadrifolia L

Rhizomes

Gajdus et al. (2014)

163.

Seven steroidal saponins

Anemarrhena asphodeloides

Rhizomes

Guo et al. (2015)

164.

Polygodosides A–F

Polygonatum odoratum

Fibrous roots

Zhang et al. (2014a, 2014b)

165.

ASC

Ophitopogin japonicas

Whole plant

Zeng et al. (2015)

166.

Smilaxchinoside A and smilaxchinoside C

Smilax riparia

Roots and Rhizomes

Wu et al. (2014a, 2014b)

167.

Sixteen steroidal saponin

Tribulus terrestris

Whole plant

Kang et al. (2014)

168.

Timosaponin X and timosaponin Y

Anemarrhena asphodeloides

Rhizomes

Yuan et al. (2014)

169.

A new steroidal saponin

Antigonon leptopus

Whole plant

Apaya and Chichioco-Hernandez (2014)

170.

Spicatoside A and spicatoside D

Liriope plathyphylla

Whole Plant

Choi et al. (2015)

171.

Ypsilandroside S and ypsilandroside T

Ypsilandra thibetica

Whole Plant

Si et al. (2014)

172.

A new C21 steroidal saponin

Azadirachta indica

Leaves

Liu et al. (2014)

173.

Four new spirostane steroidal saponins

Bletilla striata

Roots

Wang and Meng (2015)

174.

Parisverticosides A–C

Paris verticillata

Aerial parts

Sun et al. (2014)

175.

Periplocoside P

Periplocae Cortex

Whole plant

Liu et al. (2015a, 2015b)

176.

Two new furostanol saponins and a new spirostanol saponin

Tupistra chinensis

Roots and Rhizomes

Li et al. (2015a, 2015b, 2015c)

177.

Spirostane-type saponins

Dracaena fragrans

Bark, Roots and leaves

Rezgui et al. (2015)

178.

Two new steroidal saponins

Solanum paniculatum L

Aerial parts

Vieira Júnior et al. (2015)

179.

Cambodianoside G

Dracaena cambodiana

Rhizome

Luo et al. (2015)

180.

Polyhydroxy hellebosaponins

Helleborus niger L

Roots

Duckstein et al. (2014)

181.

Four new furostanol glycosides

Hosta plantaginea (Lam.) Aschers

Flowers

Li et al. (2015a, 2015b, 2015c)

182.

Trigoneoside XIIIa, parvifloside, trigoneoside IVa, deltoside, protobioside, lilioglycoside k, zingiberensis newsaponin I, deltonin, prosapogenin A of dioscin, and trillin

Dioscorea zingiberensis

Tubers

Wang et al. (2014a, 2014b, 2014c)

183.

Eight steroidal saponins

Raphia farinifera

Mesocarp of the fruits

Tapondjou et al. (2015)

184.

Three new steroidal saponins

Helleborus thibetanus

Dried roots and rhizomes

Zhang et al. (2016a, b)

185.

Two new steroidal saponins

Avena sativa

Oat Bran

Yang et al. (2016)

186.

Typaspidosides B–L

Aspidistra typica

Rhizomes

Cui et al. (2016)

187.

Chlorodeistelianosides A–D

Chlorophytum deistelianum

Aerial parts

Tabopda et al. (2016)

188.

Esculeosides B-1 and B-2

Solanum lycopersicum

Tomato juice

Nohara et al. (2015)

189.

Pratioside G and H

Polygonatum prattii

Rhizomes

Zhang et al. (2016a, 2016b)

190.

Govanoside A

Trillium govanianum

Rhizomes

Shafiq-ur-Rahman et al. (2015)

191.

Chonglouosides SL-9-SL-20

Paris polyphylla var. yunnanensis

Stems and leaves

Qin et al. (2016)

192.

TTB2

Trillium tschonoskii Maxim

Whole plant

Huang and Zou (2015)

193.

Timosaponin B-II

Anemarrhena asphodeloides

Whole plant

Yuan et al. (2015)

194.

Cynawilfosides A–I

Cynanchum wilfordii

Roots

Li et al. (2016)

195.

Two new steroidal saponins

Cestrum laevigatum L

Leaves

Ribeiro et al. (2016)

196.

Taccavietnamosides A–E

Tacca vietnamensis

Rhizomes

Yen et al. (2016)

197.

Timosaponin AIII

Anemarrhena asphodeloides Bge

Rhizomes

Wang et al. (2016a, 2016b)

198.

Methyl protodioscin

Dioscorea nipponica

Roots

Chung et al. (2016)

199.

Padelaosides C–F

Paris delavayi

Rhizomes

Liu et al. (2016a, 2016b)

200.

Terrestrinin J–T

Tribulus terrestris

Whole plant

Wang et al. (2016a, 2016b)

Transcriptome analysis of medicinal plants that produce steroidal saponins

The advent of high throughput next-generation sequencing (NGS) has made the transcriptomic analysis of plant possible with increasing speed and affordability. Transcriptome analysis of medicinal plants whose genomic information is not available in public databases helps in the identification of prospective candidate genes involved in the biosynthesis of the secondary metabolic pathway and this will further increase our understanding related to biosynthesis, regulation, and diversity of secondary metabolites. Some of the medicinal plants that were explored to understand the steroidal saponin biosynthesis are discussed below and summarized in Fig. 3.
Fig. 3

Representation of steroidal saponin-producing plant with transcriptome data: diagrammatic representation of steroidal saponin-producing non-model plants with their plant part whose comparative or non-comparative transcriptome sequencing has been performed using NGS platform. Purple star indicate more steroidal saponin accumulation and more number of upregulated transcripts related to steroidal saponin biosynthesis

Dioscorea species

Mainly steroidal saponins are found in the monocot species such as some species of Dioscoreaceae family. Steroidal saponins of this plant species, i.e., diosgenin is used as the raw material for industrial production of steroidal drugs (Lin and Yang 2008). Comparative transcriptome analysis of two high saponin-producing Dioscorea esculenta and Dioscorea cayenensis and a low saponin-producing Dioscorea alata was performed using 454 pyrosequencing to investigate steroidal saponin biosynthesis in Dioscorea species. From transcriptome analysis, it was found that DeF26G transcript was highly expressed in Dioscorea esculenta but not in Dioscorea alata. The biochemical characterization of DeF26G revealed that it was a furostanol glycoside 26-O-β-glucosidase that was involved in the conversion of protodioscin (furostanol saponin) to dioscin (spirostanol saponin). The expression of the DeF26G1 gene in the leaves of Dioscorea esculenta was higher than that in the tubers (Nakayasu et al. 2015). Using Illumina deep sequencing Dioscorea composita was used to analyze the transcriptome of 18-month-old Dioscorea composita. This information allows us to understand the biosynthetic pathway of steroidal sapogenins (diosgenin) in Dioscorea composita (Wang et al. 2015a, b, c).

Asparagus racemosus

Steroidal saponins in Asparagus racemosus mainly accumulates in the root system. The dried root of Asparagus is used as an ayurvedic medicine. The saponin present in the root of Asparagus collectively known as shatavarins. Leaf versus root transcriptome of Asparagus racemosus using Illumina sequencing approach revealed that majority of transcripts related to steroidal saponin biosynthesis including P450 and UDP-glucosyltransferase was found to be upregulated in root tissue as compared to leaf. This will lead to the hypothesis that steroidal saponin accumulated in the roots of Asparagus racemosus, which is mainly responsible for its pharmacological properties (Upadhyay et al. 2014).

Chlorophytum borivilianum

Safed musli has high saponin and polysaccharide content but the main active compound known as borivilianosides is found in roots. Steroidal saponins, borivilianosides (spirostanol type), are the major type of saponins present in Chlorophytum borivilianum. Earlier phytochemical studies indicated that initial reactions of saponins biosynthetic pathway occur in leaves, while later step modifications and storage occurs in roots (Kalra et al. 2013). Illumina HiSeq 2000 sequencing analysis of root tissue of this plant helps in the identification of candidate genes that encode enzymes controlling later stages of the saponin biosynthetic pathway and modifications (Kumar et al. 2016; Kalra et al. 2013).

Paris polyphylla

The rhizome as well as leaves and stem of Paris polyphylla is an important source of steroidal saponins. The root tissue is the main site of steroid saponin biosynthesis in Paris polyphylla so comparative transcriptome analysis was performed between 8-year-old and 4-year-old roots of Paris polyphylla. Comparative saponin biosynthesis in different aged roots showed that genes including P450 and UGTs involved in saponin biosynthesis were upregulated in the 8-year-old root, an understandable finding considering that the amount of saponin is higher in older roots (Liu et al. 2016a, b).

Trigonella foenum-graecum

The seeds and leaves of Trigonella foenum-graecum (fenugreek) are used as ayurvedic medicine in the Indian subcontinent to treat gastrointestinal ailments, high cholesterol, diabetes, wounds and inflammation. Leaves and seeds of this plant are edible and can be used as condiments (Chevallier 2000). Representational difference analysis (RDA) of cDNA of was performed using transcriptome user-friendly analysis (TRUFA, a webserver platform dedicated to RNA-seq analysis) was used to identify up-regulated genes in fenugreek in response to MeJA, cholesterol and squalene (Kornobis et al. 2015). MeJA mainly act as elicitor in plant defense under biotic and abiotic stresses. Majority of the transcripts involved in diosgenin biosynthesis including various P450 was found to be upregulated after MeJA treatment (Ciura et al. 2017) that further confirms the involvement of MeJA in the upregulation of secondary biosynthetic pathway related gene.

Trillium govanianum

Diosgenin that accumulates in rhizome as “Trillarin” is considered as the main bioactive constituent of Trillium govanianum. In addition to diosgenin govanoside, borassoside, and pennogenin were also reported to be present in the rhizome of Trillium govanianum (Rahman et al. 2015). Spatial differential expression of genes associated with steroidal saponin biosynthesis in rhizome, stem, leaf and fruit tissues of Trillium govanianum were studied using Illumina GAIIx sequencing platform. The expression analysis revealed that maximum numbers of genes are involved in saponin biosynthesis and found to be highly expressed in fruit and leaf tissues, indicating active biosynthesis of steroidal saponin takes place in fruit and leaf tissues. The downstream genes of steroidal saponin biosynthesis in leaf (SQS, CPI1, CyP5G1, FK, HDY1 and SMO2) and fruit (SQLE, SMT1, SMO1, DWF5, UGT80B1 and β-glucosidase) also showed higher expression level. These results indicate that steroidal saponins biosynthesis mainly occur in leaf and fruit tissues (Singh et al. 2017).

Allium species

Steroidal saponins were reported in more than 40 different species of allium. Tigogenin, diosgenin, alliogenin, gitogenin, agigenin, and β-chlorogenin are among the most common spirostanol sapogenins identified in the plants of allium species (Sobolewska et al. 2016). High-throughput RNA-Seq of the root, bulb and leaf tissues of Allium fistulosum with extra chromosome 2A from shallot (FF2A), monosomic addition lines (MALs) and Allium cepa aggregatum group (AA) was carried out using Illumina’s HiSeq 2500 platform to gain molecular insight into the Allium saponin biosynthesis pathway. It was observed that in FF2A line acetyl-CoA-acetyltransferase and SQS are highly expressed transcripts that are related to saponin biosynthesis. Further oxidation, hydroxylation and glycosylation steps of the saponin backbone via P450 and UGT family transcripts, respectively, were also found to be remarkably up-regulated in the FF2A line (Abdelrahman et al. 2017).

Production of steroidal saponin in culture media

Due to the limited availability of medicinal plants and slow production of medicinally important secondary metabolites, it is necessary to develop in vitro techniques for the production of bioactive compounds that can be useful for pharmacological purposes. Advances in functional genomics and application of multidisciplinary approaches help to discover new plant saponins that have different pharmacological properties. Plant cell and tissue culture methods have been explored as potentially more efficient alternatives for the production of saponin and other plant derivatives. These methods were started many years ago but the optimization of culture condition was still going on to increase the saponin production for commercial use.

In vitro culture methods to obtain steroidal saponin can be possible by optimizing plant growth regulator/plant hormone concentration in culture media, light treatment, growth conditions, precursor feeding and other parameters to obtain better results. For example, plant hormone auxin was used to induce the production of steroidal saponin solanine, solasodine and solanidine in the tissue and suspension culture of Solanum lyratum (Kuo et al. 2012). Similarly, steroidal saponin (aculeatiside A, aculeatiside B) production was observed in considerable amount in the hairy root culture of Solanum aculeatissimum under continuous light treatment for 8 weeks (Ikenaga et al. 1995). Epicotyls of Solanum aculeatissimum were used to induce callus culture and it was observed that it was able to produce steroidal saponins aculeatiside A and B (Ikenaga et al. 2000). Attempts were also made for the production of steroidal saponins from the roots of Asparagus racemosus and its callus and suspension cultures were established to produce high levels of saponins both intracellularly and extracellularly. Being an endangered species it is necessary to propagate this plant through tissue culture because traditional method of propagation through seeds is not an efficient method and it takes a lot of time. Using in vitro culture methods 20 times higher levels of saponins (shatavarins) were produced that has found to stimulate immunological response (Pise et al. 2015).

Root cultures are considered as reliable and alternative sources for the production of valuable secondary metabolites. It is easy to culture root tissues of dicot plant but in the case of monocot plants where root forms modified structures such as bulb, corm or tubers the root culture seems to be difficult but the tuberous root culture of Chlorophytum borivilianum was developed and considerable amount of saponin was quantified (Basu and Jha 2015). Effect of growth regulators was determined in the adventitious root culture of Dioscorea nipponica and it was observed that dioscin and prosapogenin C content in indole-3-butyric acid (IBA) treated roots were significantly higher as compared to 1-naphthaleneacetic acid (NAA) treated roots (Ahn et al. 2005). In in vitro shoot culture of Bacopa monnieri it was observed that application of abiotic elicitors (MeJA, salicylic acid, and CuSO4) enhances bacoside production and among these elicitors, CuSO4 was found to accumulate bacoside in a large amount (Sharma et al. 2015).

Somatic embryogenesis is a valuable technique in medicinal plant improvement programs, such as for propagation and genetic transformation. Embryogenic callus culture derived from the leaf explants of Tribulus terrestris L. accumulated steroidal saponin, i.e., diosgenin. Saponin content in embryogenic callus culture of Tribulus terrestris was found to be similar to that of seeds of naturally growing plants after the application of casein hydrolysate (CH) in growth media (Nikam et al. 2009). Fagonia indica burm was cultured in vitro on MS medium supplemented with 2,4-d for rapid regeneration of plant. Somatic embryogenesis was induced by the elimination of 2,4-dichlorophenoxyacetic acid (2,4-d) and a slight increase of 6-benzylaminopurine (BA) concentration (Ebrahimi and Payan 2013). Shoot organ culture of Yucca schidigera accumulated all kinds of sapogenins as in plant shoot but in different concentrations and their glycoside pattern was similar to that of saponins present in mature Yucca schidigera rhizome (Kaneda et al. 1987).

Steroidal saponin production in cell and tissue culture of certain plant species can also be increased by the addition of hormone or biotic and abiotic growth regulators like the production of diosgenin was stimulated by light or fungal elicitation in the cell suspension cultures of Dioscorea galeottiana when cells were grown in the dark condition. Application of low phosphate and sucrose in the growth medium results in highest production of diosgenin (Rojas et al. 1999). Diosgenin accumulation in the tissue culture of Dioscorea deltoidea was enhanced in the presence of 2,4-d (Marshall and Staba 1976).

Microbial transformation of saponin present in Dioscorea zingiberensis tubers was difficult due to the association of saponin with starch so it cannot be able to make contact with microorganisms so a combined technology of enzymatic saccharification for excluding starch from raw herb and the microbial transformation was established to prepare diosgenin from the tubers of Dioscorea zingiberensis. Using these approach saponins from Dioscorea zingiberensis was converted into diosgenin using the fungal culture of Trichoderma reesei (Zhu et al. 2010). A strain of Gibberella intermedia was also used for conversion of saponins into diosgenin by optimizing culture conditions, and using this method three times higher diosgenin yield was observed as compared to original culture media (Zhang et al. 2013a, b, c). In addition to this, nine steroidal saponins were obtained by the fermentation of total furostanol saponins from Dioscorea zingiberensis tubers incubated with the culture of a fungus Absidia coerulea. Two compounds among them show induced platelet aggregation activity due to change in their chemical structure (Pang et al. 2015). Biotransformation of total steroidal saponins of Agave sisalana into tigogenin was achieved using a rod-shaped bacterium obtained from soil samples of karst area of Guilin, China. The microbial transformation is an eco-friendly approach in the production of tigogenin (Wang et al. 2014a, b, c).

Rhizomes and roots of Ruscus aculeatus contain steroidal saponins (ruscogenins) that have several pharmacological properties. Due to its slow growth rate, complicated cultivation methods and pollination failure make this plant a vulnerable species. Ruscogenin biosynthesis in Ruscus aculeatus is greatly influenced by its clonal origin and culture type that forms the basis of its ex situ conservation (Ivanova et al. 2015). In vitro culture of Ruscus aculeatus has a potential capacity to biosynthesize steroidal saponin. Rhizome segments of this plant are used to generate calli. It was observed that young regenerated plants of about 6 weeks old have a greater capacity to biosynthesize and accumulate saponins than calli cultures and the neoruscogenin contents were found to be greater than those of ruscogenin in all samples, i.e.,plantlets and calli (Palazón et al. 2006).

It is challenging to produce saponins in the heterologous system, i.e., in microbes, and only limited successful pathway engineering attempts have been reported. The effects of several previously unexplored gene knockout targets of Saccharomyces cerevisiae were assessed for the heterologous production and to improve the production capabilities of this saponin production platform. Dramatic expansion of the endoplasmic reticulum stimulates the production of recombinant triterpene biosynthetic enzymes through disruption of the phosphatidic acid phosphatase-encoding PAH1 of Saccharomyces cerevisiae through CRISPR/Cas9 which results in the accumulation of triterpenoids and triterpene saponin (Arendt et al. 2017). Transgenic yeast strains expressing β-amyrin synthase (bAS), P450 reductase, CyP93E2 and CyP72A61v2 were able to produce soyasapogenol B, and yeast strain over expressing bAS, P450 reductase, CyP716A12 and CyP72A68v2 produce gypsogenic acid. Additionally, P450 s that seemed not to work together in planta were combinatorially expressed in transgenic yeast for the production of saponins (Fukushima et al. 2013). Combinatorial synthetic biology program was also successful for the synthesis of monoglycosylated saponins in yeast by combining CyP716Y1 with oxidosqualene cyclase, P450, and glycosyltransferase genes from different plant species (Moses et al. 2014a, b). Another transgenic yeast strain expressing dammarenediol-II synthase and protopanaxadiol synthase genes of Panax ginseng, together with a NADPH-cytochrome P450 reductase gene of Arabidopsis thaliana, were able to produce protopanaxadiol (Dai et al. 2013) and bioactive ginsenosides Rh2 or Rg3 were produced from simple sugars by microbial fermentation (Wang et al. 2015a, b, c). These platforms will provide an alternative approach to replace the traditional method of ginsenosides extraction from Panax plants. Elicitation process is another one of the most effective strategies to enhance metabolites biosynthesis and accumulation in biotechnological systems. By adopting this elicitation strategy, yeast extract can be used to elicit ginsenoside production in hairy root cultures of Panax quinquefolium (Kochan et al. 2017). Reports were available, that employ synthetic biology approach for heterologous production of triterpenoidal saponin but this technique was not reported in context of steroidal saponin production. Efforts will be made for the development of engineered yeast system that will provide an efficient system for large-scale production of steroidal saponins in near future.

Future prospects

Steroidal saponins possess a wide range of medicinal and biological properties due to the presence of structural diversity in them. To find out new plant sources of steroidal saponins and to identify the presence of new steroidal saponins in the known medicinal plants will be the area of interest of many researchers. The anti-cancerous properties of most of the steroidal saponins were already being explored widely and is still going on but the other pharmacological properties associated with this compound is yet to be investigated.

The emergence of NGS platform has revolutionized our understanding related to saponin biosynthesis especially the modification of saponin backbone. Most of the P450 s and UGTs that were involved in terpenoidal saponin biosynthesis have been characterized but identification and characterization of these two enzymes that will convert obtusifoliol to furostanol and spirostanol type of steroidal saponin are yet to be needed as they are responsible for providing different biological properties to steroidal saponins. Transcriptome data of non-model plant will be helpful in discovering new candidates of P450 s and UGTs that may be involved in the saponin backbone modification but they need to be characterized further.

The advancement in the synthetic biotechnology tools like CRISPR/Cas9-based approaches will be beneficial to engineer medicinal plants regarding secondary metabolites production and to functionally characterize the biosynthetic (backbone modifying) and regulatory enzymes related to steroidal saponin biosynthesis. Due to the lack of availability of functional mutants in most of the medicinal plants, the genome editing technology based on type II CRISPR/Cas system can be utilized to establish mutants for gene function analysis. This technique relies on Agrobacterium tumefaciens mediated transformation technology and can also be combined with Agrobacterium rhizogenes-mediated transformation. Agrobacterium rhizogenes-based Ri transformed hairy roots show the characteristics of rapid growth, reduced apical dominance, high branching, and enhanced stable production of secondary metabolites, making them a promising system for investigating biosynthesis of various secondary metabolites, especially in medicinal plants. CRISPR/Cas9 system has a wide range of applications, with more accuracy and precision as compared to other genome editing tools. This approach can be applied for converting saponin-producing plants into biofactories for mass production of saponin by diverting the flux towards steroidal biosynthetic pathway. For example, by blocking the bAS gene of triterpenoidal saponin biosynthetic pathway, phytoene synthase gene of carotenoid biosynthetic pathway or geraniol synthase gene of alkaloid biosynthesis, metabolic flux can be shifted towards steroidal saponin production. Additionally this technique will be beneficial for elucidating the function of novel P450 and UGTs. As the life cycle of saponin metabolite producing plants is generally high so Cas9 based system can further be employed to control the spatiotemporal patterns of gene expression in plants and modulating life cycles of various economically useful plants to obtain useful metabolites in short duration of time.

Saponin molecules are synthesized in plants in very trace amount that will not satisfy the needs of its commercial use and the plant sources are also very limited. So there will be the need for the production of saponins using in vitro culture methods. Tissue culture-based techniques were already being developed and need to be further optimized. Combinatorial biosynthesis of steroidal saponins in yeast system will be a part of future research and research is going on to generate semi-synthetic steroidal saponin.

Author contribution statement

SU has compiled and written the manuscript. GSJ and S have edited the manuscript. RKS has conceptualized, supervised and edited the manuscript.

Funding

Swati, Gajendra, and Shikha acknowledge CSIR-UGC for fellowship. Shukla RK would like to acknowledge SCIENCE & ENGINEERING RESEARCH BOARD EMR/2016/005256 (GAP397) for funding.

References

  1. Abbassi SJ, Vishwakarma RK, Patel P, Kumari U, Khan BM (2015) Bacopa monniera recombinant mevalonate diphosphate decarboxylase: biochemical characterization. Int J Biol Macromol 79:661–668PubMedCrossRefGoogle Scholar
  2. Abdelrahman M, El-Sayed M, Sato S, Hirakawa H, Ito SI, Tanaka K, Mine Y, Sugiyama N, Suzuki M, Yamauchi N, Shigyo M (2017) RNA-sequencing-based transcriptome and biochemical analyses of steroidal saponin pathway in a complete set of Allium fistulosumA. cepa monosomic addition lines. PLoS ONE 12:e0181784PubMedPubMedCentralCrossRefGoogle Scholar
  3. Abe I, Rohmer M, Prestwich GD (1993) Enzymatic cyclization of squalene and oxidosqualene to sterols and triterpenes. Chem Rev 93:2189–2206CrossRefGoogle Scholar
  4. Acharya D, Mitaine-Offer AC, Kaushik N, Miyamoto T, Paululat T, Mirjolet JF, Duchamp O, Lacaille-Dubois MA (2010) Steroidal saponins from Chlorophytum orchidastrum. J Nat Prod 73:7–11PubMedCrossRefGoogle Scholar
  5. Adão CR, Pereira da Silva B, Tinoco LW, Parente JP (2012) Haemolytic activity and immunological adjuvant effect of a new steroidal saponin from Allium ampeloprasum var. porrum. Chem Biodivers 9:58–67PubMedCrossRefGoogle Scholar
  6. Ahn JH, Son KH, Sohn HY, Kwon ST (2005) In vitro culture of adventitious roots from Dioscorea nipponica Makino for the production of steroidal saponins. Kor J Plant Biotechnol 32:217–223CrossRefGoogle Scholar
  7. Ahn MJ, Kim CY, Yoon KD, Ryu MY, Cheong JH, Chin YW, Kim J (2006) Steroidal saponins from the rhizomes of Polygonatum sibiricum. J Nat Prod 69:360–364PubMedCrossRefGoogle Scholar
  8. Akhtar N, Gupta P, Sangwan NS, Sangwan RS, Trivedi PK (2013) Cloning and functional characterization of 3-hydroxy-3-methylglutaryl coenzyme A reductase gene from Withania somnifera: an important medicinal plant. Protoplasma 250:613–622PubMedCrossRefGoogle Scholar
  9. Akkol EK, Tatli II, Akdemir ZS (2007) Antinociceptive and anti-inflammatory effects of saponin and iridoid glycosides from Verbascum pterocalycinum var. mutense. Hub Mor Z Naturforsch C 62:813–820PubMedCrossRefGoogle Scholar
  10. Aoyagi K, Beyou A, Moon K, Fang L, Ulrich T (1993) Isolation and characterization of cDNAs encoding wheat 3-hydroxy-3-methylglutaryl coenzyme A reductase. Plant Physiol 102:623–628PubMedPubMedCentralCrossRefGoogle Scholar
  11. Apaya MK, Chichioco-Hernandez CL (2014) New steroidal saponin from Antigonon leptopus Hook. and Arn. Pharmacogn Mag 10:S501–S505PubMedPubMedCentralCrossRefGoogle Scholar
  12. Arendt P, Miettinen K, Pollier J, De Rycke R, Callewaert N, Goossens A (2017) An endoplasmic reticulum-engineered yeast platform for overproduction of triterpenoids. Metab Eng 40:165–175PubMedCrossRefGoogle Scholar
  13. Augustin JM, Kuzina V, Andersen SB, Bak S (2011) Molecular activities, biosynthesis and evolution of triterpenoid saponins. Phytochemistry 72:435–457PubMedCrossRefGoogle Scholar
  14. Babiychuk E, Bouvier-Navé P, Compagnon V, Suzuki M, Muranaka T, Van Montagu M, Kushnir S, Schaller H (2008) Albinism and cell viability in cycloartenol synthase deficient Arabidopsis. Plant Signal Behav 3:978–980PubMedPubMedCentralCrossRefGoogle Scholar
  15. Bai H, Li W, Zhao H, Anzai Y, Li H, Guo H, Kato F, Koike K (2014) Isolation and structural elucidation of novel cholestane glycosides and spirostane saponins from Polygonatum odoratum. Steroids 80:7–14PubMedCrossRefGoogle Scholar
  16. Bak S, Kahn RA, Olsen CE, Halkier BA (1997) Cloning and expression in Escherichia coli of the obtusifoliol 14α-demethylase of Sorghum bicolor (L.) Moench, a cytochrome P450 orthologous to the sterol 14α-demethylases (CYP51) from fungi and mammals. Plant J 11:191–201PubMedCrossRefGoogle Scholar
  17. Bak S, Beisson F, Bishop G, Hamberger B, Höfer R, Paquette S, Werck-Reichhart D (2011) Cytochromes p450. Arabidopsis Book 9:e0144PubMedPubMedCentralCrossRefGoogle Scholar
  18. Basu S, Jha TB (2015) In vitro root culture: an alternative source of bioactives in the rare aphrodisiac herb Chlorophytum borivilianum Sant et Fern. Plant Tissue Cult Biotech 23:133–146Google Scholar
  19. Belhouchet Z, Sautour M, Miyamoto T, Lacaille-Dubois MA (2008) Steroidal saponins from the roots of Smilax aspera subsp. mauritanica. Chem Pharm Bull (Tokyo) 56:1324–1327CrossRefGoogle Scholar
  20. Bhattacharyya MK, Paiva NL, Dixon RA, Korth KL, Stermer BA (1995) Features of the hmg 1 subfamily of genes encoding HMG-CoA reductase in potato. Plant Mol Biol 28:1–15PubMedCrossRefGoogle Scholar
  21. Bhuvanalakshmi G, Basappa Rangappa KS, Dharmarajan A, Sethi G, Kumar AP, Warrier S (2017) Breast cancer stem-like cells are inhibited by diosgenin, a steroidal saponin, by the attenuation of the Wnt β-catenin signaling via the Wnt antagonist secreted frizzled related protein-4. Front Pharmacol 8:124PubMedPubMedCentralCrossRefGoogle Scholar
  22. Cabello-Hurtado F, Taton M, Forthoffer N, Kahn R, Bak S, Rahier A, Werck-Reichhart D (1999) Optimized expression and catalytic properties of a wheat obtusifoliol 14α-demethylase (CYP51) expressed in yeast. Complementation of erg11Delta yeast mutants by plant CYP51. Eur J Biochem 262:435–446PubMedCrossRefGoogle Scholar
  23. Cao X, Zong Z, Ju X, Sun Y, Dai C, Liu Q, Jiang J (2010) Molecular cloning, characterization and function analysis of the gene encoding HMG-CoA reductase from Euphorbia Pekinensis Rupr. Mol Biol Rep 37:1559–1567PubMedCrossRefGoogle Scholar
  24. Challinor VL, De Voss JJ (2013) Open-chain steroidal glycosides, a diverse class of plant saponins. Nat Prod Rep 30:429–454PubMedCrossRefGoogle Scholar
  25. Challinor VL, Stuthe JM, Bernhardt PV, Lehmann RP, Kitching W, De Voss JJ (2011) Structure and absolute configuration of helosides A and B, new saponins from Chamaelirium luteum. J Nat Prod 74:1557–1560PubMedCrossRefGoogle Scholar
  26. Challinor VL, Parsons PG, Chap S, White EF, Blanchfield JT, Lehmann RP, De Voss JJ (2012a) Steroidal saponins from the roots of Smilax sp.: structure and bioactivity. Steroids 77:504–511PubMedCrossRefGoogle Scholar
  27. Challinor VL, Piacente S, De Voss JJ (2012b) NMR assignment of the absolute configuration of C-25 in furostanol steroidal saponins. Steroids 77:602–608PubMedCrossRefGoogle Scholar
  28. Challinor VL, Stuthe JM, Parsons PG, Lambert LK, Lehmann RP, Kitching W, De Voss JJ (2012c) Structure and bioactivity of steroidal saponins isolated from the roots of Chamaelirium luteum (false unicorn). J Nat Prod 75:1469–1479PubMedCrossRefGoogle Scholar
  29. Chan JY, Koon JC, Liu X, Detmar M, Yu B, Kong SK, Fung KP (2011) Polyphyllin D, a steroidal saponin from Paris polyphylla, inhibits endothelial cell functions in vitro and angiogenesis in zebrafish embryos in vivo. J Ethnopharmacol 137:64–69PubMedCrossRefGoogle Scholar
  30. Chen HF, Wang GH, Luo Q, Wang NL, Yao XS (2009) Two new steroidal saponins from Allium macrostemon bunge and their cytotoxity on different cancer cell lines. Molecules 14:2246–2253PubMedCrossRefGoogle Scholar
  31. Chen G, Chen H, Li W, Pei YH (2011a) Steroidal glycosides from Cynanchum amplexicaule. J Asian Nat Prod Res 13:756–760PubMedCrossRefGoogle Scholar
  32. Chen PY, Chen CH, Kuo CC, Lee TH, Kuo YH, Lee CK (2011b) Cytotoxic steroidal saponins from Agave sisalana. Planta Med 77:929–933PubMedCrossRefGoogle Scholar
  33. Chen G, Yi S, Hua HM, Lu X, Pei YH (2012) Two new steroidal glycosides from Cynanchum amplexicaule. J Asian Nat Prod Res 14:559–563PubMedCrossRefGoogle Scholar
  34. Chen G, Su L, Feng SG, Lu X, Wang H, Pei YH (2013) Furostanol saponins from the fruits of Tribulus terrestris. Nat Prod Res 27:1186–1190PubMedCrossRefGoogle Scholar
  35. Chen Y, Tang YM, Yu SL, Han YW, Kou JP, Liu BL, Yu BY (2015) Advances in the pharmacological activities and mechanisms of diosgenin. Chin J Nat Med 13:578–587PubMedGoogle Scholar
  36. Chen MH, Chen XJ, Wang M, Lin LG, Wang YT (2016) Ophiopogon japonicus—A phytochemical, ethnomedicinal and pharmacological review. J Ethnopharmacol 181:193–213PubMedCrossRefGoogle Scholar
  37. Cheng ZH, Wu T, Yu BY (2006) Steroidal glycosides from tubers of Ophiopogon japonicus. J Asian Nat Prod Res 8:555–559PubMedCrossRefGoogle Scholar
  38. Chevallier A (2000) Encyclopedia of herbal medicine. Dorling Kindersley Publishing, New York, p 271Google Scholar
  39. Choi DW, Jung J, Ha YI, Park HW, In DS, Chung HJ, Liu JR (2005) Analysis of transcripts in methyl jasmonate-treated ginseng hairy roots to identify genes involved in the biosynthesis of ginsenosides and other secondary metabolites. Plant Cell Rep 23:557–566PubMedCrossRefGoogle Scholar
  40. Choi SJ, Choi J, Jeon H, Bae SK, Ko J, Kim J, Yoon KD (2015) Application of high-performance countercurrent chromatography for the isolation of steroidal saponins from Liriope plathyphylla. J Sep Sci 38:18–24PubMedCrossRefGoogle Scholar
  41. Chung YL, Pan CH, Wang CC, Hsu KC, Sheu MJ, Chen HF, Wu CH (2016) Methyl protodioscin, a steroidal saponin, inhibits neointima formation in vitro and in vivo. J Nat Prod 79:1635–1644PubMedCrossRefGoogle Scholar
  42. Chye ML, Kush A, Tan CT, Chua NH (1991) Characterization of cDNA and genomic clones encoding 3-hydroxy-3-methylglutaryl-coenzyme A reductase from Hevea brasiliensis. Plant Mol Biol 16:567–577PubMedCrossRefGoogle Scholar
  43. Ciura J, Szeliga M, Grzesik M, Tyrka M (2017) Next-generation sequencing of representational difference analysis products for identification of genes involved in diosgenin biosynthesis in fenugreek (Trigonella foenum-graecum). Planta 245:977–991PubMedPubMedCentralCrossRefGoogle Scholar
  44. Colmenares AP, Rojas LB, Mitaine-Offer AC, Pouységu L, Quideau S, Miyamoto T, Tanaka C, Paululat T, Usubillaga A, Lacaille-Dubois MA (2013) Steroidal saponins from the fruits of Solanum torvum. Phytochemistry 86:137–143PubMedCrossRefGoogle Scholar
  45. Cordoba E, Porta H, Arroyo A, San Román C, Medina L, Rodriguez-Concepcion M, León P (2011) Functional characterization of the three genes encoding 1-deoxy-d-xylulose 5-phosphate synthase in maize. J Exp Bot 62:2023–2038PubMedCrossRefGoogle Scholar
  46. Cui JM, Kang LP, Zhao Y, Zhao JY, Zhang J, Pang X, Yu HS, Jia DX, Liu C, Yu LY, Ma BP (2016) Steroidal saponins from the rhizomes of Aspidistra typica. PLoS ONE 11:e0150595PubMedPubMedCentralCrossRefGoogle Scholar
  47. Dai Z, Cui G, Zhou SF, Zhang X, Huang L (2011) Cloning and characterization of a novel 3-hydroxy-3-methylglutaryl coenzyme A reductase gene from Salvia miltiorrhiza involved in diterpenoid tanshinone accumulation. J Plant Physiol 168:148–157PubMedCrossRefGoogle Scholar
  48. Dai Z, Liu Y, Zhang X, Shi M, Wang B, Wang D, Huang L, Zhang X (2013) Metabolic engineering of Saccharomyces cerevisiae for production of ginsenosides. Metab Eng 20:146–156PubMedCrossRefGoogle Scholar
  49. De Lucca AJ, Boue S, Palmgren MS, Maskos K, Cleveland TE (2006) Fungicidal properties of two saponins from Capsicum frutescens and the relationship of structure and fungicidal activity. Can J Microbiol 52:336–342PubMedCrossRefGoogle Scholar
  50. De Marino S, Festa C, Zollo F, Iorizzi M (2012) Novel steroidal components from the underground parts of Ruscus aculeatus L. Molecules 17:14002–14014PubMedCrossRefGoogle Scholar
  51. Deng D, Lauren DR, Cooney JM, Jensen DJ, Wurms KV, Upritchard JE, Cannon RD, Wang MZ, Li MZ (2008) Antifungal saponins from Paris polyphylla Smith. Planta Med 74:1397–1402PubMedCrossRefGoogle Scholar
  52. Dhar N, Rana S, Razdan S, Bhat WW, Hussain A, Dhar RS, Vaishnavi S, Hamid A, Vishwakarma R, Lattoo SK (2014) Cloning and functional characterization of three branch point oxidosqualene cyclases from Withania somnifera (L.) dunal. J Biol Chem 289:17249–17267PubMedPubMedCentralCrossRefGoogle Scholar
  53. Diab Y, Ioannou E, Emam A, Vagias C, Roussis V (2012) Desmettianosides A and B, bisdesmosidic furostanol saponins with molluscicidal activity from Yucca desmettiana. Steroids 77:686–690PubMedCrossRefGoogle Scholar
  54. Diarra ST, He J, Wang J, Li J (2013) Ethylene treatment improves diosgenin accumulation in in vitro cultures of Dioscorea zingiberensis via up-regulation of CAS and HMGR gene expression. Elect J Biotech 16:1–10Google Scholar
  55. Duckstein SM, Lorenz P, Conrad J, Stintzing FC (2014) Tandem mass spectrometric characterization of acetylated polyhydroxy hellebosaponins, the principal steroid saponins in Helleborus niger L. roots. Rapid Commun Mass Spectrom 28:1801–1812PubMedCrossRefGoogle Scholar
  56. Ebrahimi MA, Payan A (2013) Induction of callus and somatic embryogenesis from cotyledon explants of Fagonia indica Burm. J Med Plants By Prod 2:209–214Google Scholar
  57. El-Sayed MM, Abdel-Hameed ES, El-Nahas HA, El-Wakil EA (2006) Isolation and identification of some steroidal glycosides of Furcraea selloa. Pharmazie 61:478–482PubMedGoogle Scholar
  58. Eskander J, Lavaud C, Harakat D (2010) Steroidal saponins from the leaves of Agave macroacantha. Fitoterapia 81:371–374PubMedCrossRefGoogle Scholar
  59. Eskander J, Lavaud C, Harakat D (2011) Steroidal saponins from the leaves of Beaucarnea recurvata. Phytochemistry 72:946–951PubMedCrossRefGoogle Scholar
  60. Fabris M, Matthijs M, Carbonelle S, Moses T, Pollier J, Dasseville R, Baart GJ, Vyverman W, Goossens A (2014) Tracking the sterol biosynthesis pathway of the diatom Phaeodactylum tricornutum. New Phytol 204:521–535PubMedCrossRefGoogle Scholar
  61. Folwarczna J, Zych M, Nowińska B, Pytlik M, Bialik M, Jagusiak A, Lipecka-Karcz M, Matysiak M (2016) Effect of diosgenin, a steroidal sapogenin, on the rat skeletal system. Acta Biochim Pol 63:287–295PubMedCrossRefGoogle Scholar
  62. Fouad MA, Mohamed KM, Kamel MS, Matsunami K, Otsuka H (2008) Cesdiurins I-III, steroidal saponins from Cestrum diurnum L. J Nat Med 62:168–173PubMedCrossRefGoogle Scholar
  63. Fukushima EO, Seki H, Sawai S, Suzuki M, Ohyama K, Saito K, Muranaka T (2013) Combinatorial biosynthesis of legume natural and rare triterpenoids in engineered yeast. Plant Cell Physiol 54(5):740–749PubMedCrossRefGoogle Scholar
  64. Fuller S, Stephens JM (2015) Diosgenin, 4-hydroxyisoleucine, and fiber from fenugreek: mechanisms of actions and potential effects on metabolic syndrome. Adv Nutr 6:189–197PubMedPubMedCentralCrossRefGoogle Scholar
  65. Gajdus J, Kaczyński Z, Kawiak A, Lojkowska E, Stefanowicz-Hajduk J, Ochocka JR, Stepnowski P (2014) Isolation and identification of cytotoxic compounds from the rhizomes of Paris quadrifolia L. Pharmacogn Mag 10:S324–S333PubMedPubMedCentralCrossRefGoogle Scholar
  66. Galarraga E, Mitaine-Offer AC, Amaro-Luis JM, Miyamoto T, Tanaka C, Pouységu L, Quideau S, Rojas LB, Lacaille-Dubois MA (2011) Steroidal saponins from the fruits of Cestrum ruizteranianum. Nat Prod Commun 6:1825–1826PubMedGoogle Scholar
  67. Gas-Pascual E, Berna A, Bach TJ, Schaller H (2014) Plant oxidosqualene metabolism: cycloartenol synthase-dependent sterol biosynthesis in Nicotiana benthamiana. PLoS ONE 9:e109156PubMedPubMedCentralCrossRefGoogle Scholar
  68. Gnoula C, Mégalizzi V, De Nève N, Sauvage S, Ribaucour F, Guissou P, Duez P, Dubois J, Ingrassia L, Lefranc F, Kiss R, Mijatovic T (2008) Balanitin-6 and -7: diosgenyl saponins isolated from Balanites aegyptiaca Del. display significant anti-tumor activity in vitro and in vivo. Int J Oncol 32:5–15PubMedGoogle Scholar
  69. Gong Y, Liao Z, Chen M, Zuo K, Guo L, Tan Q, Huang Z, Kai G, Sun X, Tan F, Tang K (2005) Molecular cloning and characterization of a 1-deoxy-d-xylulose 5-phosphate reductoisomerase gene from Ginkgo biloba. DNA Seq 16:111–120PubMedCrossRefGoogle Scholar
  70. Gruenweller S, Schroeder E, Kesselmeier J (1990) Biological activities of furostanol saponins from Nicotiana tabacum. Phytochemistry 29:2485–2490CrossRefGoogle Scholar
  71. Guclu Ustundag O, Mazza G (2007) Saponins: properties, applications and processing. Crit Rev Food Sci Nutr 47:231–258PubMedCrossRefGoogle Scholar
  72. Guo Y, Liu YX, Kang LP, Zhang T, Yu HS, Zhao Y, Xiong CQ, Ma BP (2013) Two novel furostanol saponins from the tubers of Ophiopogon japonicus. J Asian Nat Prod Res 15:459–465PubMedCrossRefGoogle Scholar
  73. Guo J, Xu C, Xue R, Jiang W, Wu B, Huang C (2015) Cytotoxic activities of chemical constituents from rhizomes of Anemarrhena asphodeloides and their analogues. Arch Pharm Res 38:598–603PubMedCrossRefGoogle Scholar
  74. Guo H, Li R, Liu S, Zhao N, Han S, Lu M, Liu X, Xia X (2016) Molecular characterization, expression, and regulation of Gynostemma pentaphyllum squalene epoxidase gene 1. Plant Physiol Biochem 109:230–239PubMedCrossRefGoogle Scholar
  75. Ha SH, Lee SW, Kim YM, Hwang YS (2001) Molecular characterization of Hmg2 gene encoding a 3-hydroxy-methylglutaryl-CoA reductase in rice. Mol Cells 11:295–302PubMedGoogle Scholar
  76. Ha SH, Kim JB, Hwang YS, Lee SW (2003) Molecular characterization of three 3-hydroxy-3-methylglutaryl-CoA reductase genes including pathogen-induced Hmg2 from pepper (Capsicum annuum). Biochim Biophys Acta 1625:253–260PubMedCrossRefGoogle Scholar
  77. Han JY, In JG, Kwon YS, Choi YE (2010) Regulation of ginsenoside and phytosterol biosynthesis by RNA interferences of squalene epoxidase gene in Panax ginseng. Phytochemistry 71:36–46PubMedCrossRefGoogle Scholar
  78. Haralampidis K, Trojanowska M, Osbourn AE (2002) Biosynthesis of triterpenoid saponins in plants. Adv Biochem Eng Biotechnol 75:31–49PubMedGoogle Scholar
  79. Hayes PY, Lambert LK, Lehmann R, Penman K, Kitching W, De Voss JJ (2007) Complete (1)H and (13)C assignments of the four major saponins from Dioscorea villosa (wild yam). Magn Reson Chem 45:1001–1005PubMedCrossRefGoogle Scholar
  80. Hayes PY, Jahidin AH, Lehmann R, Penman K, Kitching W, De Voss JJ (2008) Steroidal saponins from the roots of Asparagus racemosus. Phytochemistry 69:796–804PubMedCrossRefGoogle Scholar
  81. Hayes PY, Lehmann R, Penman K, Kitching W, De Voss JJ (2009) Steroidal saponins from the roots of Trillium erectum (Beth root). Phytochemistry 70:105–113PubMedCrossRefGoogle Scholar
  82. He H, Sun YP, Zheng L, Yue ZG (2015) Steroidal saponins from Paris polyphylla induce apoptotic cell death and autophagy in A549 human lung cancer cells. Asian Pac J Cancer Prev 16:1169–1173PubMedCrossRefGoogle Scholar
  83. Hong XX, Luo JG, Guo C, Kong LY (2012) New steroidal saponins from the bulbs of Lilium brownii var. viridulum. Carbohydr Res 361:19–26PubMedCrossRefGoogle Scholar
  84. Hostettmann K, Marston A (1995) Saponins. Cambridge University Press, CambridgeCrossRefGoogle Scholar
  85. Hostettmann K, Marston A (2005) Saponins, chemistry and pharmacology of natural products. Cambridge University Press, CambridgeGoogle Scholar
  86. Huang X, Kong L (2006) Steroidal saponins from roots of Asparagus officinalis. Steroids 71:171–176PubMedCrossRefGoogle Scholar
  87. Huang W, Zou K (2015) Cytotoxicity of the saponin TTB2 on Ewing sarcoma cells. Exp Ther Med 10:625–628PubMedPubMedCentralCrossRefGoogle Scholar
  88. Huang HL, Liu RH, Shao F (2009) Structural determination of two new steroidal saponins from Smilax china. Magn Reson Chem 47:741–745PubMedCrossRefGoogle Scholar
  89. Huang HC, Lin MK, Hwang SY, Hwang TL, Kuo YH, Chang CI, Ou CY, Kuo YH (2013) Two anti-inflammatory steroidal saponins from Dracaena angustifolia Roxb. Molecules 18:8752–8763PubMedCrossRefGoogle Scholar
  90. Ikenaga T, Oyama T, Muranaka T (1995) Growth and steroidal saponin production in hairy root cultures of Solanum aculeatissimum. Plant Cell Rep 14:413–417PubMedCrossRefGoogle Scholar
  91. Ikenaga T, Handayani R, Oyama T (2000) Steroidal saponin production in callus cultures of Solanum aculeatissimum Jacq. Plant Cell Rep 19:1240–1244CrossRefGoogle Scholar
  92. Inoue K, Shimomura K, Kobayashi S, Sankawa U, Ebizuka Y (1996) Conversion of furostanol glycoside to spirostanol glycoside by β-glucosidase in Costus speciosus. Phytochemistry 41:725–727CrossRefGoogle Scholar
  93. Ivanova A, Mikhova B, Klaiber I, Dinchev D, Kostova I (2009) Steroidal saponins from Smilax excelsa rhizomes. Nat Prod Res 23:916–924PubMedCrossRefGoogle Scholar
  94. Ivanova T, Dimitrova D, Gussev C, Bosseva Y, Stoeva T (2015) Ex situ conservation of Ruscus aculeatus L.—ruscogenin biosynthesis, genome-size stability and propagation traits of tissue-cultured clones. Biotechnol Biotechnol Equip 29:27–32PubMedPubMedCentralCrossRefGoogle Scholar
  95. Jain AK, Vincent RM, Nessler CL (2000) Molecular characterization of a hydroxymethylglutaryl-CoA reductase gene from mulberry (Morus alba L.). Plant Mol Biol 42:559–569PubMedCrossRefGoogle Scholar
  96. Jayachandran KS, Vasanthi AH, Gurusamy N (2016) Steroidal saponin diosgenin from Dioscorea bulbifera protects cardiac cells from hypoxia-reoxygenation Injury through modulation of pro-survival and pro-death molecules. Pharmacogn Mag 12:14–20CrossRefGoogle Scholar
  97. Jeena GS, Fatima S, Tripathi P, Upadhyay S, Shukla RK (2017) Comparative transcriptome analysis of shoot and root tissue of Bacopa monnieri identifies potential genes related to triterpenoid saponin biosynthesis. BMC Genom 18:490CrossRefGoogle Scholar
  98. Jiang D, Rong Q, Chen Y, Yuan Q, Shen Y, Guo J, Yang Y, Zha L, Wu H, Huang L, Liu C (2017) Molecular cloning and functional analysis of squalene synthase (SS) in Panax notoginseng. Int J Biol Macromol 95:658–666PubMedCrossRefGoogle Scholar
  99. Jin H, Gong Y, Guo B, Qiu C, Liu D, Miao Z, Sun X, Tang K (2006) Isolation and characterization of a 2C-methyl-d-erythritol 2, 4-cyclodiphosphate synthase gene from Taxus media. Mol Biol (Mosk) 40:1013–1020CrossRefGoogle Scholar
  100. Jin YL, Kuk JH, Oh KT, Kim YJ, Piao XL, Park RD (2007) A new steroidal saponin, yuccalan, from the leaves of Yucca smalliana. Arch Pharm Res 30:543–546PubMedCrossRefGoogle Scholar
  101. Jones RN, Katzenellenbogen E, Dobriner K (1953) Steroid metabolism. XVII. The infrared absorption spectra of the steroid sapogenins. J Am Chem Soc 75:158–166CrossRefGoogle Scholar
  102. Kalita R, Patar L, Shasany AK, Modi MK, Sen P (2015) Molecular cloning, characterization and expression analysis of 3-hydroxy-3-methylglutaryl coenzyme A reductase gene from Centella asiatica L. Mol Biol Rep 42:1431–1439PubMedCrossRefGoogle Scholar
  103. Kalra S, Kumar S, Lakhanpal N, Kaur J, Singh K (2013) Characterization of Squalene synthase gene from Chlorophytum borivilianum (Sant. and Fernand.). Mol Biotechnol 54:944–953PubMedCrossRefGoogle Scholar
  104. Kaneda N, Nakanishi H, Staba EJ (1987) Steroidal constituents of Yucca shidigera plants and tissue cultures. Phytochemistry 26:1425–1429CrossRefGoogle Scholar
  105. Kang LP, Ma BP, Shi TJ, Zhang J, Xiong CQ (2006) Two new furostanol saponins from the rhizomes of Anemarrhena asphodeloides. Yao Xue Xue Bao 41:527–532PubMedGoogle Scholar
  106. Kang YJ, Chung HJ, Nam JW, Park HJ, Seo EK, Kim YS, Lee D, Lee SK (2011) Cytotoxic and antineoplastic activity of timosaponin A-III for human colon cancer cells. J Nat Prod 74:701–706PubMedCrossRefGoogle Scholar
  107. Kang LP, Liu YX, Eichhorn T, Dapat E, Yu HS, Zhao Y, Xiong CQ, Liu C, Efferth T, Ma BP (2012a) Polyhydroxylated steroidal glycosides from Paris polyphylla. J Nat Prod 75:1201–1205PubMedCrossRefGoogle Scholar
  108. Kang LP, Wang YZ, Feng B, Huang HZ, Zhou WB, Zhao Y, Xiong CQ, Tan DW, Song XB, Ma BP (2012b) Structure elucidation and complete NMR spectral assignments of glucosylated saponins of cantalasaponin I. Magn Reson Chem 50:79–83PubMedCrossRefGoogle Scholar
  109. Kang LP, Zhang J, Cong Y, Li B, Xiong CQ, Zhao Y, Tan DW, Yu HS, Yu ZY, Cong YW, Liu C, Ma BP (2012c) Steroidal glycosides from the rhizomes of Anemarrhena asphodeloides and their antiplatelet aggregation activity. Planta Med 78:611–616PubMedCrossRefGoogle Scholar
  110. Kang LP, Wu KL, Yu HS, Pang X, Liu J, Han LF, Zhang J, Zhao Y, Xiong CQ, Song XB, Liu C, Cong YW, Ma BP (2014) Steroidal saponins from Tribulus terrestris. Phytochemistry 107:182–189PubMedCrossRefGoogle Scholar
  111. Kawabata T, Cui MY, Hasegawa T, Takano F, Ohta T (2011) Anti-inflammatory and anti-melanogenic steroidal saponin glycosides from Fenugreek (Trigonella foenum-graecum L.) seeds. Planta Med 77:705–710PubMedCrossRefGoogle Scholar
  112. Keim V, Manzano D, Fernández FJ, Closa M, Andrade P, Caudepón D, Bortolotti C, Vega MC, Arró M, Ferrer A (2012) Characterization of Arabidopsis FPS isozymes and FPS gene expression analysis provide insight into the biosynthesis of isoprenoid precursors in seeds. PLoS ONE 7:e49109PubMedPubMedCentralCrossRefGoogle Scholar
  113. Kim SM, Kuzuyama T, Chang YJ, Kim SU (2006) Cloning and characterization of 2-C-methyl-d-erythritol 2,4-cyclodiphosphate synthase (MECS) gene from Ginkgo biloba. Plant Cell Rep 25:829–835PubMedCrossRefGoogle Scholar
  114. Kim TD, Han JY, Huh GH, Choi YE (2011) Expression and functional characterization of three squalene synthase genes associated with saponin biosynthesis in Panax ginseng. Plant Cell Physiol 52:125–137PubMedCrossRefGoogle Scholar
  115. Kim CS, Kim SY, Moon E, Lee MK, Lee KR (2013) Steroidal constituents from the leaves of Hosta longipes and their inhibitory effects on nitric oxide production. Bioorg Med Chem Lett 15:1771–1775CrossRefGoogle Scholar
  116. Kim YJ, Lee OR, Oh JY, Jang MG, Yang DC (2014) Functional analysis of 3-hydroxy-3-methylglutaryl coenzyme A reductase encoding genes in triterpene saponin-producing ginseng. Plant Physiol 165:373–387PubMedPubMedCentralCrossRefGoogle Scholar
  117. Kim JE, Go J, Koh EK, Song SH, Sung JE, Lee HA, Kim DS, Son HJ, Lee HS, Lee CY, Hong JT, Hwang DY (2016) Diosgenin effectively suppresses skin inflammation induced by phthalic anhydride in IL-4/Luc/CNS-1 transgenic mice. Biosci Biotechnol Biochem 80:891–901PubMedCrossRefGoogle Scholar
  118. Kime B, Barminas JT, Nkafamiya II, Akinterinwa A (2015) Extraction and evaluation of a saponin-based surfactant from Balanites aegyptiaca plant as an emulsifying agent. Int J Innov Sci Eng Technol 2:733–737Google Scholar
  119. Kirmizibekmez H, Masullo M, Festa M, Capasso A, Piacente S (2014) Steroidal glycosides with antiproliferative activities from Digitalis trojana. Phytother Res 28:534–538PubMedCrossRefGoogle Scholar
  120. Kitagawa I (2002) Licorice root. A natural sweetener and an important ingredient in Chinese medicine. Pure Appl Chem 74:1189–1198CrossRefGoogle Scholar
  121. Kochan E, Szymczyk P, Kuźma Ł, Lipert A, Szymańska G (2017) Yeast extract stimulates ginsenoside production in hairy root cultures of American ginseng cultivated in shake flasks and nutrient sprinkle bioreactors. Molecules 22(6):880CrossRefGoogle Scholar
  122. Kohara A, Nakajima C, Hashimoto K, Ikenaga T, Tanaka H, Shoyama Y, Yoshida S, Muranaka T (2005) A novel glucosyltransferase involved in steroid saponin biosynthesis in Solanum aculeatissimum. Plant Mol Biol 57:225–239PubMedCrossRefGoogle Scholar
  123. Kornobis E, Cabellos L, Aguilar F, Frias-Lopez C, Rozas J, Marco J, Zardoya R (2015) TRUFA: a user-friendly web server for de novo RNA-seq analysis using cluster computing. Evol Bioinform 11:97–104CrossRefGoogle Scholar
  124. Kostadinova EP, Alipieva KI, Kokubun T, Taskova RM, Handjieva NV (2007) Phenylethanoids, iridoids and a spirostanol saponin from Veronica turrilliana. Phytochemistry 68:1321–1326PubMedCrossRefGoogle Scholar
  125. Kougan GB, Miyamoto T, Tanaka C, Paululat T, Mirjolet JF, Duchamp O, Sondengam BL, Lacaille-Dubois MA (2010) Steroidal saponins from two species of Dracaena. J Nat Prod 73:1266–1270PubMedCrossRefGoogle Scholar
  126. Kowalczyk M, Pecio Ł, Stochmal A, Oleszek W (2011) Qualitative and quantitative analysis of steroidal saponins in crude extract and bark powder of Yucca schidigera Roezl. J Agric Food Chem 59:8058–8064PubMedCrossRefGoogle Scholar
  127. Kumar S, Kalra S, Singh B, Kumar A, Kaur J, Singh K (2016) RNA-Seq mediated root transcriptome analysis of Chlorophytum borivilianum for identification of genes involved in saponin biosynthesis. Funct Integr Genom 16:37–55CrossRefGoogle Scholar
  128. Kumari U, Vishwakarma RK, Sonawane P, Abbassi S, Khan BM (2015) Biochemical characterization of recombinant mevalonate kinase from Bacopa monniera. Int J Biol Macromol 72:776–783PubMedCrossRefGoogle Scholar
  129. Kuo CI, Chao CH, Lu MK (2012) Effects of auxins on the production of steroidal alkaloids in rapidly proliferating tissue and cell cultures of Solanum lyratum. Phytochem Anal 23:400–404PubMedCrossRefGoogle Scholar
  130. Kuroda M, Ori K, Mimaki Y (2006) Ornithosaponins A–D, four new polyoxygenated steroidal glycosides from the bulbs of Ornithogalum thyrsoides. Steroids 71:199–205PubMedCrossRefGoogle Scholar
  131. Lai W, Wu Z, Lin H, Li T, Sun L, Chai Y, Chen W (2010) Anti-ischemia steroidal saponins from the seeds of Allium fistulosum. J Nat Prod 73:1053–1057PubMedCrossRefGoogle Scholar
  132. Lakshmi V, Kumar R, Pandey K, Joshi BS, Roy R, Madhusudanan KP, Tiwari P, Srivastava AK (2009) Structure and activities of a steroidal saponin from Chlorophytum nimonii (Grah) Dalz. Nat Prod Res 23:963–972PubMedCrossRefGoogle Scholar
  133. Laranjeira S, Amorim-Silva V, Esteban A, Arró M, Ferrer A, Tavares RM, Botella MA, Rosado A, Azevedo H (2015) Arabidopsis squalene epoxidase 3 (SQE3) complements SQE1 and is important for embryo development and bulk squalene epoxidase activity. Mol Plant 8:1090–1102PubMedCrossRefGoogle Scholar
  134. Lee B, Trinh HT, Jung K, Han SJ, Kim DH (2010) Inhibitory effects of steroidal timosaponins isolated from the rhizomes of Anemarrhena asphodeloides against passive cutaneous anaphylaxis reaction and pruritus. Immunopharmacol Immunotoxicol 32:357–363PubMedCrossRefGoogle Scholar
  135. Lee CL, Hwang TL, He WJ, Tsai YH, Yen CT, Yen HF, Chen CJ, Chang WY, Wu YC (2013) Anti-neutrophilic inflammatory steroidal glycosides from Solanum torvum. Phytochemistry 95:315–321PubMedCrossRefGoogle Scholar
  136. Li X, Sun H, Ye Y, Chen F, Pan Y (2006) C-21 steroidal glycosides from the roots of Cynanchum chekiangense and their immunosuppressive activities. Steroids 71:61–66PubMedCrossRefGoogle Scholar
  137. Li H, Huang W, Wen Y, Gong G, Zhao Q, Yu G (2010) Anti-thrombotic activity and chemical characterization of steroidal saponins from Dioscorea zingiberensis CH Wright. Fitoterapia 81:1147–1156PubMedCrossRefGoogle Scholar
  138. Li N, Zhang L, Zeng KW, Zhou Y, Zhang JY, Che YY, Tu PF (2013) Cytotoxic steroidal saponins from Ophiopogon japonicus. Steroids 78:1–7PubMedCrossRefGoogle Scholar
  139. Li XJ, Wang L, Xue PF, Xie HX, Wei H, Wang J (2015a) New steroidal glycosides from Hosta plantaginea (Lam.) Aschers. J Asian Nat Prod Res 17:224–231PubMedCrossRefGoogle Scholar
  140. Li Y, Liu C, Xiao D, Han J, Yue Z, Sun Y, Fan L, Zhang F, Meng J, Zhang R, Wang Z, Mei Q, Wen A (2015b) Trillium tschonoskii steroidal saponins suppress the growth of colorectal cancer cells in vitro and in vivo. J Ethnopharmacol 168:136–145PubMedCrossRefGoogle Scholar
  141. Li Y, Wang X, He H, Zhang D, Jiang Y, Yang X, Wang F, Tang Z, Song X, Yue Z (2015c) Steroidal saponins from the roots and rhizomes of Tupistra chinensis. Molecules 20:13659–13669PubMedCrossRefGoogle Scholar
  142. Li JL, Gao ZB, Zhao WM (2016) Identification and evaluation of antiepileptic activity of C21 steroidal glycosides from the roots of Cynanchum wilfordii. J Nat Prod 79:89–97PubMedCrossRefGoogle Scholar
  143. Liang M, Zheng Z, Yuan Y, Kong L, Shen Y, Liu R, Zhang C, Zhang W (2007) Identification and quantification of C21 steroidal saponins from Radix Cynanchi Atrati by high-performance liquid chromatography with evaporative light scattering detection and electrospray mass spectrometric detection. Phytochem Anal 18:428–435PubMedCrossRefGoogle Scholar
  144. Liang Y, Jiang X, Hu Q, Li X, Yin H, Li D, Zhang Y, Liu X (2014) Cloning and characterization of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) gene from Paris fargesii Franch. Indian J Biochem Biophys 51:201–206PubMedGoogle Scholar
  145. Lin JT, Yang DJ (2008) Determination of steroidal saponins in different organs of yam (Dioscorea pseudojaponica Yamamoto). Food Chem 108:1068–1074PubMedCrossRefGoogle Scholar
  146. Lin S, Wang D, Yang D, Yao J, Tong Y, Chen J (2007) Characterization of steroidal saponins in crude extract from Dioscorea nipponica Makino by liquid chromatography tandem multi-stage mass spectrometry. Anal Chim Acta 599:98–106PubMedCrossRefGoogle Scholar
  147. Lin T, Huang HL, Liu RH, Shu JC, Ren G, Shao F, Liu LS (2012) Steroidal saponins and pregnane glycosides from Smilax microphylla. Magn Reson Chem 50:813–817PubMedCrossRefGoogle Scholar
  148. Liu HY, Ni W, Hao XJ, Chen CX (2006) Steroidal saponins from Tacca plantaginea. J Asian Nat Prod Res 8:293–298PubMedCrossRefGoogle Scholar
  149. Liu T, Chen G, Yi GQ, Xu JK, Zhang TL, Hua HM, Pei YH (2010a) New pregnane and steroidal glycosides from Tribulus terrestris L. J Asian Nat Prod Res 12:209–214PubMedCrossRefGoogle Scholar
  150. Liu T, Lu X, Wu B, Chen G, Hua HM, Pei YH (2010b) Two new steroidal saponins from Tribulus terrestris L. J Asian Nat Prod Res 12:30–35PubMedCrossRefGoogle Scholar
  151. Liu H, Chou GX, Wang JM, Ji LL, Wang ZT (2011) Steroidal saponins from the rhizomes of Dioscorea bulbifera and their cytotoxic activity. Planta Med 77:845–848PubMedCrossRefGoogle Scholar
  152. Liu CX, Guo ZY, Xue YH, Zhang HY, Zhang HQ, Zou K, Huang NY (2012a) Tupisteroide A–C, three new polyhydroxylated steroidal constituents from the roots of Tupistra chinensis. Magn Reson Chem 50:320–324PubMedCrossRefGoogle Scholar
  153. Liu X, Zhang H, Niu XF, Xin W, Qi L (2012b) Steroidal saponins from Smilacina japonica. Fitoterapia 83:812–816PubMedCrossRefGoogle Scholar
  154. Liu QB, Peng Y, Li LZ, Gao PY, Sun Y, Yu LH, Song SJ (2013) Steroidal saponins from Anemarrhena asphodeloides. J Asian Nat Prod Res 15:891–898PubMedCrossRefGoogle Scholar
  155. Liu L, Zhao YL, Cheng GG, Chen YY, Qin XJ, Song CW, Yang XW, Liu YP, Luo XD (2014) Limonoid and steroidal saponin from Azadirachta indica. Nat Prod Bioprospect 4:335–340PubMedPubMedCentralCrossRefGoogle Scholar
  156. Liu JY, Lu L, Kang LP, Liu YX, Zhao Y, Xiong CQ, Zhang YQ, Yu LY, Ma BP (2015a) Selective glycosylation of steroidal saponins by Arthrobacter nitroguajacolicus. Carbohydr Res 402:71–76PubMedCrossRefGoogle Scholar
  157. Liu Y, Ouyang Y, Wang ZQ, Qiao L, Li S, Zhao SH, Liu MY (2015b) A new C21 steroidal saponins from Periplocae Cortex. Zhongguo Zhong Yao Za Zhi 40:455–457PubMedGoogle Scholar
  158. Liu T, Li X, Xie S, Wang L, Yang S (2016a) RNA-seq analysis of Paris polyphylla var. yunnanensis roots identified candidate genes for saponin synthesis. Plant Divers 38:163–170CrossRefPubMedPubMedCentralGoogle Scholar
  159. Liu Y, Tian X, Hua D, Cheng G, Wang K, Zhang L, Tang H, Wang M (2016b) New steroidal saponins from the rhizomes of Paris delavayi and their cytotoxicity. Fitoterapia 111:130–137PubMedCrossRefGoogle Scholar
  160. Liu M, Li LN, Pan YT, Kong JQ (2017) cDNA isolation and functional characterization of squalene synthase gene from Ornithogalum caudatum. Protein Expr Purif 130:63–72PubMedCrossRefGoogle Scholar
  161. Lorent JH, Quetin-Leclercq J, Mingeot-Leclercq MP (2014) The amphiphilic nature of saponins and their effects on artificial and biological membranes and potential consequences for red blood and cancer cells. Org Biomol Chem 12:8803–8822PubMedCrossRefGoogle Scholar
  162. Lu Y, Luo J, Huang X, Kong L (2009) Four new steroidal glycosides from Solanum torvum and their cytotoxic activities. Steroids 74:95–101PubMedCrossRefGoogle Scholar
  163. Lu Y, Chen CX, Ni W, Hua Y, Liu HY (2010) Spirostanol tetraglycosides from Ypsilandra thibetica. Steroids 75:982–987PubMedCrossRefGoogle Scholar
  164. Lu Y, Luo J, Kong L (2011) Steroidal alkaloid saponins and steroidal saponins from Solanum surattense. Phytochemistry 72:668–673PubMedCrossRefGoogle Scholar
  165. Luo Y, Shen HY, Zuo WJ, Wang H, Mei WL, Dai HF (2015) A new steroidal saponin from dragon’s blood of Dracaena cambodiana. J Asian Nat Prod Res 17:409–414PubMedCrossRefGoogle Scholar
  166. Ma S, Kou J, Yu B (2011) Safety evaluation of steroidal saponin DT-13 isolated from the tuber of Liriope muscari (Decne.) Baily. Food Chem Toxicol 49:2243–2251PubMedCrossRefGoogle Scholar
  167. Maldonado-Mendoza IE, Vincent RM, Nessler CL (1997) Molecular characterization of three differentially expressed members of the Camptotheca acuminata 3-hydroxy-3-methylglutaryl CoA reductase (HMGR) gene family. Plant Mol Biol 34:781–790PubMedCrossRefGoogle Scholar
  168. Mandal D, Banerjee S, Mondal NB, Chakravarty AK, Sahu NP (2006) Steroidal saponins from the fruits of Asparagus racemosus. Phytochemistry 67:1316–1321PubMedCrossRefGoogle Scholar
  169. Marshall JG, Staba EJ (1976) Hormonal effects on diosgenin biosynthesis and growth in Dioscorea deltoidea tissue cultures. Phytochemistry 15:53–55CrossRefGoogle Scholar
  170. Masullo M, Pizza C, Piacente S (2016) Ruscus genus: a rich source of bioactive steroidal saponins. Planta Med 82:1513–1524PubMedCrossRefGoogle Scholar
  171. Matsuo Y, Watanabe K, Mimaki Y (2008) New steroidal glycosides from rhizomes of Clintonia udensis. Biosci Biotechnol Biochem 72:1714–1721PubMedCrossRefGoogle Scholar
  172. Moehs CP, Allen PV, Friedman M, Belknap WR (1997) Cloning and expression of solanidine UDP-glucose glucosyltransferase from potato. Plant J 11:227–236PubMedCrossRefGoogle Scholar
  173. Moharram FA, EI-Shenawy SM (2007) Antinociceptive and anti-inflammatory steroidal saponins from Dracaena ombet. Planta Med 73:1101–1106PubMedCrossRefGoogle Scholar
  174. Montes EG, Mitaine-Offer AC, Amaro-Luis JM, Paululat T, Delaude C, Pouységu L, Quideau S, Rojas LB, Delemasure S, Dutartre P, Lacaille-Dubois MA (2014) Acylated oleanane-type saponins from Ganophyllum giganteum. Phytochemistry 98:236–242PubMedCrossRefGoogle Scholar
  175. Morrissey JP, Osbourn AE (1999) Fungal resistance to plant antibiotics as a mechanism of pathogenesis. Microbiol Mol Biol Rev 63:708–724PubMedPubMedCentralGoogle Scholar
  176. Moses T, Papadopoulou KK, Osbourn A (2014a) Metabolic and functional diversity of saponins, biosynthetic intermediates and semi-synthetic derivatives. Crit Rev Biochem Mol Biol 49:439–462PubMedPubMedCentralCrossRefGoogle Scholar
  177. Moses T, Pollier J, Almagro L, Buyst D, Van Montagu M, Pedreño MA, Martins JC, Thevelein JM, Goossens A (2014b) Combinatorial biosynthesis of sapogenins and saponins in Saccharomyces cerevisiae using a C-16α hydroxylase from Bupleurum falcatum. Proc Natl Acad Sci USA 111(4):1634–1639PubMedCrossRefGoogle Scholar
  178. Mskhiladze L, Kutchukhidze J, Chincharadze D, Delmas F, Elias R, Favel A (2008a) In vitro antifungal and antileishmanial activities of steroidal saponins from Allium leucanthum C. Koch—a Caucasian endemic species. Georgian Med News 154:39–43Google Scholar
  179. Mskhiladze L, Legault J, Lavoie S, Mshvildadze V, Kuchukhidze J, Elias R, Pichette A (2008b) Cytotoxic steroidal saponins from the flowers of Allium leucanthum. Molecules 13:2925–2934PubMedCrossRefGoogle Scholar
  180. Munafo JP, Ramanathan A, Jimenez LS, Gianfagna TJ (2010) Isolation and structural determination of steroidal glycosides from the bulbs of Easter lily (Lilium longiflorum Thunb.). J Agric Food Chem 58:8806–8813PubMedCrossRefGoogle Scholar
  181. Nakamura S, Hongo M, Sugimoto S, Matsuda H, Yoshikawa M (2008) Steroidal saponins and pseudoalkaloid oligoglycoside from Brazilian natural medicine, “fruta do lobo” (fruit of Solanum lycocarpum). Phytochemistry 69:1565–1572PubMedCrossRefGoogle Scholar
  182. Nakayasu M, Kawasaki T, Lee HJ, Sugimoto Y, Onjo M, Muranaka T, Mizutani M (2015) Identification of furostanol glycoside 26-O-β-glucosidase involved in steroidal saponin biosynthesis from Dioscorea esculenta. Plant Biotechnol 32:299–308CrossRefGoogle Scholar
  183. Napolitano A, Muzashvili T, Perrone A, Pizza C, Kemertelidze E, Piacente S (2010) Steroidal glycosides from Ruscus ponticus. Phytochemistry 72:651–661CrossRefGoogle Scholar
  184. Naveed MA, Riaz N, Saleem M, Jabeen B, Ashraf M, Ismail T, Jabbar A (2014) Longipetalosides A–C, new steroidal saponins from Tribulus longipetalus. Steroids 83:45–51PubMedCrossRefGoogle Scholar
  185. Nelson D (2006) Plant cytochrome P450 s from moss to poplar. Phytochem Rev 5:193–204CrossRefGoogle Scholar
  186. Nian H, Qin LP, Chen WS, Zhang QY, Zheng HC, Wang Y (2006) Protective effect of steroidal saponins from rhizome of Anemarrhena asphodeloides on ovariectomy-induced bone loss in rats. Acta Pharmacol Sin 27:728–734PubMedCrossRefGoogle Scholar
  187. Nikam TD, Ebrahimi MA, Patil VA (2009) Embryogenic callus culture of Tribulus terrestris L. a potential source of harmaline, harmine and diosgenin. Plant Biotechnol Rep 3:243–250CrossRefGoogle Scholar
  188. Nohara T, Ono M, Ikeda T, Fujiwara Y, El-Aasr M (2010) The tomato saponin, esculeoside A. J Nat Prod 73:1734–1741PubMedCrossRefGoogle Scholar
  189. Nohara T, Fujiwara Y, Zhou JR, Urata J, Ikeda T, Murakami K, El-Aasr M, Ono M (2015) Saponins, esculeosides B-1 and B-2, in tomato juice and sapogenol, esculeogenin B1. Chem Pharm Bull (Tokyo) 63:848–850CrossRefGoogle Scholar
  190. Ohnishi T, Yokota T, Mizutani M (2009) Insights into the function and evolution of P450 s in plant steroid metabolism. Phytochemistry 70:1918–1929PubMedCrossRefGoogle Scholar
  191. Ohno M, Ono M, Nohara T (2011) New solanocapsine-type tomato glycoside from ripe fruit of Solanum lycopersicum. Chem Pharm Bull (Tokyo) 59:1403–1405CrossRefGoogle Scholar
  192. Ohtsuki T, Sato M, Koyano T, Kowithayakorn T, Kawahara N, Goda Y, Ishibashi M (2006) Steroidal saponins from Calamus insignis, and their cell growth and cell cycle inhibitory activities. Bioorg Med Chem 14:659–665PubMedCrossRefGoogle Scholar
  193. Osbourn AE (1996) Preformed antimicrobial compounds and plant defense against fungal attack. Plant Cell 8:1821–1831PubMedPubMedCentralCrossRefGoogle Scholar
  194. Osbourn AE (2003) Saponins in cereals. Phytochemistry 62:1–4PubMedCrossRefGoogle Scholar
  195. Palazón J, Moyano E, Bonfill M, Osuna LT, Cusidó RM, Pinol MT (2006) Effect of organogenesis on steroidal saponin biosynthesis in calli cultures of Ruscus aculeatus. Fitoterapia 77:216–220PubMedCrossRefGoogle Scholar
  196. Pan X, Chen M, Liu Y, Wang Q, Zeng L, Li L, Liao Z (2008) A new isopentenyl diphosphate isomerase gene from Camptotheca acuminata: cloning, characterization and functional expression in Escherichia coli. DNA Seq 19:98–105PubMedCrossRefGoogle Scholar
  197. Pan ZH, Li Y, Liu JL, Ning DS, Li DP, Wu XD, Wen YX (2012) A cytotoxic cardenolide and a saponin from the rhizomes of Tupistra chinensis. Fitoterapia 83:1489–1493PubMedCrossRefGoogle Scholar
  198. Pang X, Wen D, Zhao Y, Xiong CQ, Wang XQ, Yu LY, Ma BP (2015) Steroidal saponins obtained by biotransformation of total furostanol glycosides from Dioscorea zingiberensis with Absidia coerulea. Carbohydr Res 402:236–240PubMedCrossRefGoogle Scholar
  199. Paquette SM, Bak S, Feyereisen R (2000) Intron–exon organization and phylogeny in a large superfamily, the paralogous cytochrome P450 genes of Arabidopsis thaliana. DNA Cell Biol 19:307–317PubMedCrossRefGoogle Scholar
  200. Pecio Ł, Jędrejek D, Masullo M, Piacente S, Oleszek W, Stochmal A (2012) Revised structures of avenacosides A and B and a new sulfated saponin from Avena sativa L. Magn Reson Chem 50:755–758PubMedCrossRefGoogle Scholar
  201. Peng YR, Li YB, Liu XD, Zhang JF, Duan JA (2008) Antitumor activity of C-21 steroidal glycosides from Cynanchum auriculatum Royle ex Wight. Phytomedicine 15:1016–1020PubMedCrossRefGoogle Scholar
  202. Pereira BD, Valente AP, Parente JP (2004) A new steroidal saponin from Agave shrevei. Nat Prod Res 20:385–390CrossRefGoogle Scholar
  203. Pérez AJ, Calle JM, Simonet AM, Guerra JO, Stochmal A, Macías FA (2013) Bioactive steroidal saponins from Agave offoyana flowers. Phytochemistry 95:298–307PubMedCrossRefGoogle Scholar
  204. Pérez AJ, Simonet AM, Calle JM, Pecio Ł, Guerra JO, Stochmal A, Macías FA (2014) Phytotoxic steroidal saponins from Agave offoyana leaves. Phytochemistry 105:92–100PubMedCrossRefGoogle Scholar
  205. Perez-Labrada K, Brouard I, Estévez S, Marrero MT, Estévez F, Bermejo J, Rivera DG (2012) New insights into the structure–cytotoxicity relationship of spirostan saponins and related glycosides. Bioorg Med Chem 20:2690–2700PubMedCrossRefGoogle Scholar
  206. Phillips MA, D’Auria JC, Gershenzon J, Pichersky E (2008) The Arabidopsis thaliana type I isopentenyl diphosphate isomerases are targeted to multiple subcellular compartments and have overlapping functions in isoprenoid biosynthesis. Plant Cell 20:677–696PubMedPubMedCentralCrossRefGoogle Scholar
  207. Pise MV, Rudra JA, Upadhyay A (2015) Immunomodulatory potential of shatavarins produced from Asparagus racemosus tissue cultures. J Nat Sci Biol Med 6:415–420PubMedPubMedCentralCrossRefGoogle Scholar
  208. Qin Y, Wu X, Huang W, Gong G, Li D, He Y, Zhao Y (2009) Acute toxicity and sub-chronic toxicity of steroidal saponins from Dioscorea zingiberensis C.H.Wright in rodents. J Ethnopharmacol 126:543–550PubMedCrossRefGoogle Scholar
  209. Qin XJ, Sun DJ, Ni W, Chen CX, Hua Y, He L, Liu HY (2012) Steroidal saponins with antimicrobial activity from stems and leaves of Paris polyphylla var. yunnanensis. Steroids 77:1242–1248PubMedCrossRefGoogle Scholar
  210. Qin XJ, Yu MY, Ni W, Yan H, Chen CX, Cheng YC, He L, Liu HY (2016) Steroidal saponins from stems and leaves of Paris polyphylla var. yunnanensis. Phytochemistry 121:20–29PubMedCrossRefGoogle Scholar
  211. Qu Y, Zhang Y, Pei L, Wang Y, Gao L, Huang Q, Ojika M, Sakagami Y, Qi J (2011) New neuritogenic steroidal saponin from Ophiopogon japonicus (Thunb.) Ker-Gawl. Biosci Biotechnol Biochem 75:1201–1204PubMedCrossRefGoogle Scholar
  212. Rahman SU, Ismail M, Khurram M, Haq IU (2015) Pharmacognostic and ethnomedicinal studies on Trillium govanianum. Pak J Bot 47:187–192Google Scholar
  213. Ramalingam M, Kim SJ (2016) Pharmacological activities and applications of spicatoside A. Biomol Ther (Seoul) 24:469–474CrossRefGoogle Scholar
  214. Ramos-Valdivia AC, van der Heijden R, Verpoorte R, Camara B (1997) Purification and characterization of two isoforms of isopentenyl-diphosphate isomerase from elicitor-treated Cinchona robusta cells. Eur J Biochem 249:161–170PubMedCrossRefGoogle Scholar
  215. Razdan S, Bhat WW, Rana S, Dhar N, Lattoo SK, Dhar RS, Vishwakarma RA (2013) Molecular characterization and promoter analysis of squalene epoxidase gene from Withania somnifera (L.) Dunal. Mol Biol Rep 40:905–916PubMedCrossRefGoogle Scholar
  216. Rezgui A, Mitaine-Offer AC, Pertuit D, Miyamoto T, Tanaka C, Delemasure S, Dutartre P, Lacaille-Dubois MA (2013) Steroidal saponins from Dracaena marginata. Nat Prods Commun 8:157–160Google Scholar
  217. Rezgui A, Mitaine-Offer AC, Paululat T, Delemasure S, Dutartre P, Lacaille-Dubois MA (2014) Cytotoxic steroidal glycosides from Allium flavum. Fitoterapia 93:121–125PubMedCrossRefGoogle Scholar
  218. Rezgui A, Mitaine-Offer AC, Miyamoto T, Tanaka C, Lacaille-Dubois MA (2015) Spirostane-type saponins from Dracaena fragrans “Yellow Coast”. Nat Prod Commun 10:37–38PubMedGoogle Scholar
  219. Ribeiro PR, Araújo AJ, Costa-Lotufo LV, Braz-Filho R, Nobre Junior HV, da Silva CR, de Andrade Neto JB, Silveira ER, Lima MA (2016) Spirostanol glucosides from the leaves of Cestrum laevigatum L. Steroids 106:35–40PubMedCrossRefGoogle Scholar
  220. Rojas R, Alba J, Magaña-Plaza I, Cruz F, Ramos-Valdivia AC (1999) Stimulated production of diosgenin in Dioscorea galeottiana cell suspension cultures by abiotic and biotic factors. Biotechnol Lett 21:907–911CrossRefGoogle Scholar
  221. Rong Q, Xu Q, Liu C, Huang L (2011) Cloning and characterization of 3-hydroxy-3-methylglutary CoA reductase cDNA of Glycyrrhiza uralensis. Zhongguo Zhong Yao Za Zhi 36:1275–1279PubMedGoogle Scholar
  222. Rong Q, Jiang D, Chen Y, Shen Y, Yuan Q, Lin H, Zha L, Zhang Y, Huang L (2016) Molecular cloning and functional analysis of squalene synthase 2 (SQS2) in Salvia miltiorrhiza Bunge. Front Plant Sci 7:1274PubMedPubMedCentralGoogle Scholar
  223. Sautour M, Miyamoto T, Lacaille-Dubois MA (2006) Bioactive steroidal saponins from Smilax medica. Planta Med 72:667–670PubMedCrossRefGoogle Scholar
  224. Sautour M, Miyamoto T, Lacaille-Dubois MA (2007) Steroidal saponins from Asparagus acutifolius. Phytochemistry 68:2554–2562PubMedCrossRefGoogle Scholar
  225. Sawai S, Saito K (2011) Triterpenoid biosynthesis and engineering in plants. Front Plant Sci 2:25PubMedPubMedCentralCrossRefGoogle Scholar
  226. Schuler M (1996) Plant cytochrome P450 monooxygenases. Crit Rev Plant Sci 15:235–284CrossRefGoogle Scholar
  227. Schulte AE, van der Heijden R, Verpoorte R (2000) Purification and characterization of mevalonate kinase from suspension-cultured cells of Catharanthus roseus (L) G Don. Arch Biochem Biophys 378:287–298PubMedCrossRefGoogle Scholar
  228. Shao B, Guo H, Cui Y, Ye M, Han J, Guo D (2007) Steroidal saponins from Smilax china and their anti-inflammatory activities. Phytochemistry 68:623–630PubMedCrossRefGoogle Scholar
  229. Sharma U, Saini R, Kumar N, Singh B (2009) Steroidal saponins from Asparagus racemosus. Chem Pharm Bull (Tokyo) 57:890–893CrossRefGoogle Scholar
  230. Sharma U, Kumar N, Singh B (2012) Furostanol saponin and diphenylpentendiol from the roots of Asparagus racemosus. Nat Prod Commun 7:995–998PubMedGoogle Scholar
  231. Sharma M, Ahuja A, Gupta R, Mallubhotla S (2015) Enhanced bacoside production in shoot cultures of Bacopa monnieri under the influence of abiotic elicitors. Nat Prod Res 29:745–749PubMedCrossRefGoogle Scholar
  232. Shen G, Pang Y, Wu W, Liao Z, Zhao L, Sun X, Tang K (2006) Cloning and characterization of a root-specific expressing gene encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase from Ginkgo biloba. Mol Biol Rep 33:117–127PubMedCrossRefGoogle Scholar
  233. Shen S, Chen CJ, Bu R, Ga L, Li GY, Tan Y, Li X, Wang JH (2011) Three new steroidal saponins from Fritillaria pallidiflora. J Asian Nat Prod Res 13:1014–1022PubMedCrossRefGoogle Scholar
  234. Shen S, Li G, Huang J, Chen C, Ren B, Lu G, Tan Y, Zhang J, Li X, Wang J (2012) Steroidal saponins from Fritillaria pallidiflora Schrenk. Fitoterapia 83:785–794PubMedCrossRefGoogle Scholar
  235. Shen HY, Zuo WJ, Wang H, Zhao YX, Guo ZK, Luo Y, Li XN, Dai HF, Mei WL (2014) Steroidal saponins from dragon’s blood of Dracaena cambodiana. Fitoterapia 94:94–101PubMedCrossRefGoogle Scholar
  236. Shen T, Qiu F, Chen M, Lan XZ, Liao ZH (2015) Cloning and functional characterization of a cDNA encoding isopentenyl diphosphate isomerase involved in taxols biosynthesis in Taxus media. Yao Xue Xue Bao 50:621–626PubMedGoogle Scholar
  237. Shu W, Wu C, Zhang Y, Ye WC, Zhou G (2013) Two new steroidal glycosides isolated from the aerial part of Solanum torvum Swartz. Nat Prod Res 27:1982–1986PubMedCrossRefGoogle Scholar
  238. Shwe HH, Aye M, Sein MM, Htay KT, Kreitmeier P, Gertsch J, Reiser O, Heilmann J (2010) Cytotoxic steroidal saponins from the rhizomes of Tacca integrifolia. Chem Biodivers 7:610–622PubMedCrossRefGoogle Scholar
  239. Si YA, Yan H, Ni W, Liu ZH, Lu TX, Cheng CX, Liu HY (2014) Two new steroidal saponins from Ypsilandra thibetica. Nat Prod Bioprospect 4:315–318PubMedPubMedCentralCrossRefGoogle Scholar
  240. Singh P, Singh G, Bhandawat A, Singh G, Parmar R, Seth R, Sharma RK (2017) Spatial transcriptome analysis provides insights of key gene(s) involved in steroidal saponin biosynthesis in medicinally important herb Trillium govanianum. Sci Rep 7:45295PubMedPubMedCentralCrossRefGoogle Scholar
  241. Skhirtladze A, Perrone A, Montoro P, Benidze M, Kemertelidze E, Pizza C, Piacente S (2011) Steroidal saponins from Yucca gloriosa L. rhizomes: LC–MS profiling, isolation and quantitative determination. Phytochemistry 72:126–135PubMedCrossRefGoogle Scholar
  242. Sobolewska D, Janeczko Z, Kisiel W, Podolak I, Galanty A, Trojanowska D (2006) Steroidal glycosides from the underground parts of Allium ursinum L. and their cytostatic and antimicrobial activity. Acta Pol Pharm 63:219–223PubMedGoogle Scholar
  243. Sobolewska D, Michalska K, Podolak I, Grabowska K (2016) Steroidal saponins from the genus Allium. Phytochem Rev 15:1–35PubMedCrossRefGoogle Scholar
  244. Su L, Chen G, Feng SG, Wang W, Li ZF, Chen H, Liu YX, Pei YH (2009) Steroidal saponins from Tribulus terrestris. Steroids 74:399–403PubMedCrossRefGoogle Scholar
  245. Sun LX, Fu WW, Li W, Bi KS, Wang MW (2006) Diosgenin glucuronides from Solanum lyratum and their cytotoxicity against tumor cell lines. Z Naturforsch C 61:171–176PubMedCrossRefGoogle Scholar
  246. Sun Z, Huang X, Kong L (2010) A new steroidal saponin from the dried stems of Asparagus officinalis L. Fitoterapia 81:210–213PubMedCrossRefGoogle Scholar
  247. Sun K, Cao S, Pei L, Matsuura A, Xiang L, Qi J (2013) A steroidal saponin from Ophiopogon japonicus extends the lifespan of yeast via the pathway involved in SOD and UTH1. Int J Mol Sci 14:4461–4475PubMedPubMedCentralCrossRefGoogle Scholar
  248. Sun CL, Ni W, Yan H, Liu ZH, Yang L, Si YA, Hua Y, Chen CX, He L, Zhao JH, Liu HY (2014) Steroidal saponins with induced platelet aggregation activity from the aerial parts of Paris verticillata. Steroids 92:90–95PubMedCrossRefGoogle Scholar
  249. Suzuki M, Kamide Y, Nagata N, Seki H, Ohyama K, Kato H, Masuda K, Sato S, Kato T, Tabata S, Yoshida S, Muranaka T (2004) Loss of function of 3-hydroxy-3-methylglutaryl coenzyme A reductase 1 (HMG1) in Arabidopsis leads to dwarfing, early senescence and male sterility, and reduced sterol levels. Plant J 37:750–761PubMedCrossRefGoogle Scholar
  250. Tabopda TK, Mitaine-Offer AC, Tanaka C, Miyamoto T, Mirjolet JF, Duchamp O, Ngadjui BT, Lacaille-Dubois MA (2014) Steroidal saponins from Dioscorea preussii. Fitoterapia 97:198–203PubMedCrossRefGoogle Scholar
  251. Tabopda TK, Mitaine-Offer AC, Paululat T, Delemasure S, Dutartre P, Ngadjui BT, Lacaille-Dubois MA (2016) Steroidal saponins from Chlorophytum deistelianum. Phytochemistry 126:34–40PubMedCrossRefGoogle Scholar
  252. Tan DW, Kang LP, Lü N, Zhang J, Ma BP (2006) Study on steroidal saponins of Dioscorea septemloba thumb. Zhong Yao Cai 29:1176–1179PubMedGoogle Scholar
  253. Tang W, Newton RJ (2006) Mevalonate kinase activity during different stages of plant regeneration from nodular callus cultures in white pine (Pinus strobus). Tree Physiol 26:195–200PubMedCrossRefGoogle Scholar
  254. Tapondjou LA, Ponou KB, Teponno RB, Mbiantcha M, Djoukeng JD, Nguelefack TB, Watcho P, Cadenas AG, Park HJ (2008) In vivo anti-inflammatory effect of a new steroidal saponin, mannioside A, and its derivatives isolated from Dracaena mannii. Arch Pharm Res 31:653–658PubMedCrossRefGoogle Scholar
  255. Tapondjou LA, Jenett-Siems K, Böttger S, Melzig MF (2013) Steroidal saponins from the flowers of Dioscorea bulbifera var. sativa. Phytochemistry 95:341–350PubMedCrossRefGoogle Scholar
  256. Tapondjou LA, Siems KJ, Böttger S, Melzig MF (2015) Steroidal saponins from the mesocarp of the fruits of Raphia farinifera (Arecaceae) and their cytotoxic activity. Nat Prod Commun 10:1941–1944PubMedGoogle Scholar
  257. Temraz AE, Gindi OD, Kadry HA, De Tommasi N, Braca A (2006) Steroidal saponins from the aerial parts of Tribulus alatus Del. Phytochemistry 67:1011–1018PubMedCrossRefGoogle Scholar
  258. Timité G, Mitaine-Offer AC, Miyamoto T, Tanaka C, Mirjolet JF, Duchamp O, Lacaille-Dubois MA (2013) Structure and cytotoxicity of steroidal glycosides from Allium schoenoprasum. Phytochemistry 88:61–66PubMedCrossRefGoogle Scholar
  259. Tiski I, Marraccini P, Pot D, Vieira LG, Pereira LF (2011) Characterization and expression of two cDNA encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase isoforms in coffee (Coffea arabica L.). OMICS 15:719–727PubMedCrossRefGoogle Scholar
  260. Tong QY, He Y, Zhao QB, Qing Y, Huang W, Wu XH (2012) Cytotoxicity and apoptosis-inducing effect of steroidal saponins from Dioscorea zingiberensis Wright against cancer cells. Steroids 77:1219–1227PubMedCrossRefGoogle Scholar
  261. Tong YR, Su P, Zhao YJ, Zhang M, Wang XJ, Hu TY, Gao W, Huang LQ (2015) Cloning and expression analysis of 4- (cytidine-5-diphospho) -2-C-methyl-D-erythritol kinase gene in Tripterygium wilfordii. Zhongguo Zhong Yao Za Zhi 40:4165–4170PubMedGoogle Scholar
  262. Tong Y, Zhang M, Su P, Zhao Y, Wang X, Zhang X, Gao W, Huang L (2016) Cloning and functional characterization of an isopentenyl diphosphate isomerase gene from Tripterygium wilfordii. Biotechnol Appl Biochem 63:863–869PubMedCrossRefGoogle Scholar
  263. Uchida H, Sugiyama R, Nakayachi O, Takemura M, Ohyama K (2007) Expression of the gene for sterol-biosynthesis enzyme squalene epoxidase in parenchyma cells of the oil plant, Euphorbia tirucalli. Planta 226:1109–1115PubMedCrossRefGoogle Scholar
  264. Upadhyay S, Phukan UJ, Mishra S, Shukla RK (2014) De novo leaf and root transcriptome analysis identified novel genes involved in steroidal sapogenin biosynthesis in Asparagus racemosus. BMC Genom 15:746CrossRefGoogle Scholar
  265. Vieira Júnior GM, da Rocha CQ, de Souza Rodrigues T, Hiruma-Lima CA, Vilegas W (2015) New steroidal saponins and antiulcer activity from Solanum paniculatum L. Food Chem 186:160–167PubMedCrossRefGoogle Scholar
  266. Vincken JP, Heng L, de Groot A, Gruppen H (2007) Saponins, classification and occurrence in the plant kingdom. Phytochemistry 68:275–297PubMedCrossRefGoogle Scholar
  267. Vishwakarma RK, Patel KA, Sonawane P, Singh S, Ruby Kumari U, Agrawal DC, Khan BM (2012) Molecular characterization of farnesyl pyrophosphate synthase from Bacopa monniera by comparative modeling and docking studies. Bioinformation 8:1075–1081PubMedPubMedCentralCrossRefGoogle Scholar
  268. Waheed A, Barker J, Barton SJ, Owen CP, Ahmed S, Carew MA (2012) A novel steroidal saponin glycoside from Fagonia indica induces cell-selective apoptosis or necrosis in cancer cells. Eur J Pharm Sci 47:464–473PubMedCrossRefGoogle Scholar
  269. Wang Y, McAllister TA (2010) A modified spectrophotometric assay to estimate deglycosylation of steroidal saponin to sapogenin by mixed ruminal microbes. J Sci Food Agric 90:1811–1818PubMedGoogle Scholar
  270. Wang W, Meng H (2015) Cytotoxic, anti-inflammatory and hemostatic spirostane-steroidal saponins from the ethanol extract of the roots of Bletilla striata. Fitoterapia 101:12–18PubMedCrossRefGoogle Scholar
  271. Wang Y, Guo B, Zhang F, Yao H, Miao Z, Tang K (2007) Molecular cloning and functional analysis of the gene encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase from hazel (Corylus avellana L. Gasaway). J Biochem Mol Biol 40:861–869PubMedGoogle Scholar
  272. Wang D, Li D, Zhu W, Zhang J, Peng P (2009a) Steroidal saponins from the rhizomes of Polygonatum odoratum. Nat Prod Res 23:940–947PubMedCrossRefGoogle Scholar
  273. Wang Y, Qiu C, Zhang F, Guo B, Miao Z, Sun X, Tang K (2009b) Molecular cloning, expression profiling and functional analyses of a cDNA encoding isopentenyl diphosphate isomerase from Gossypium barbadense. Biosci Rep 29:111–119PubMedCrossRefGoogle Scholar
  274. Wang YZ, Feng B, Huang HZ, Kang LP, Cong Y, Zhou WB, Zou P, Cong YW, Song XB, Ma BP (2010) Glucosylation of steroidal saponins by cyclodextrin glucanotransferase. Planta Med 76:1724–1731PubMedCrossRefGoogle Scholar
  275. Wang K, Sasaki T, Li W, Li Q, Wang Y, Asada Y, Kato H, Koike K (2011a) Two novel steroidal alkaloid glycosides from the seeds of Lycium barbarum. Chem Biodivers 8:2277–2284PubMedCrossRefGoogle Scholar
  276. Wang KW, Zhang H, Shen LQ, Wang W (2011b) Novel steroidal saponins from Liriope graminifolia (Linn.) Baker with anti-tumor activities. Carbohydr Res 346:253–258PubMedCrossRefGoogle Scholar
  277. Wang H, Zhai Z, Li N, Jin H, Chen J, Yuan S, Wang L, Zhang J, Li Y, Yun J, Fan J, Yi J, Ling R (2013) Steroidal saponin of Trillium tschonoskii reverses multidrug resistance of hepatocellular carcinoma. Phytomedicine 20:985–991PubMedCrossRefGoogle Scholar
  278. Wang JJ, Liu YX, Wen D, Yu HS, Kang LP, Pang X, Ma BP, Chen YD (2014a) Study on steroidal saponins from Dioscorea zingiberensis and their platelet aggregation activities. Zhongguo Zhong Yao Za Zhi 39:3782–3787PubMedGoogle Scholar
  279. Wang QJ, Zheng LP, Zhao PF, Zhao YL, Wang JW (2014b) Cloning and characterization of an elicitor-responsive gene encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase involved in 20-hydroxyecdysone production in cell cultures of Cyanotis arachnoidea. Plant Physiol Biochem 84:1–9PubMedCrossRefGoogle Scholar
  280. Wang Y, Li X, Sun H, Yi K, Zheng J, Zhang J, Hao Z (2014c) Biotransformation of steroidal saponins in sisal (Agave sisalana Perrine) to tigogenin by a newly isolated strain from a karst area of Guilin, China. Biotechnol Biotechnol Equip 28:1024–1033PubMedPubMedCentralCrossRefGoogle Scholar
  281. Wang P, Wei Y, Fan Y, Liu Q, Wei W, Yang C, Zhang L, Zhao G, Yue J, Yan X, Zhou Z (2015a) Production of bioactive ginsenosides Rh2 and Rg3 by metabolically engineered yeasts. Metab Eng 29:97–105PubMedCrossRefGoogle Scholar
  282. Wang X, Chen D, Wang Y, Xie J (2015b) De novo transcriptome assembly and the putative biosynthetic pathway of steroidal sapogenins of Dioscorea composita. PLoS ONE 10:e0124560PubMedPubMedCentralCrossRefGoogle Scholar
  283. Wang YH, Niu HM, Zhang ZY, Hu XY, Li H (2015c) Medicinal values and their chemical bases of Paris. Zhongguo Zhong Yao Za Zhi 40:833–839PubMedGoogle Scholar
  284. Wang Y, Xu L, Lou LL, Song SJ, Yao GD, Ge MY, Hayashi T, Tashiro SI, Onodera S, Ikejima T (2016a) Timosaponin AIII induces apoptosis and autophagy in human melanoma A375-S2 cells. Arch Pharm Res 40:69–78PubMedCrossRefGoogle Scholar
  285. Wang ZF, Wang BB, Zhao Y, Wang FX, Sun Y, Guo RJ, Song XB, Xin HL, Sun XG (2016b) Furostanol and spirostanol saponins from Tribulus terrestris. Molecules 21:E429PubMedCrossRefGoogle Scholar
  286. Williams JR, Gong H (2007) Biological activities and syntheses of steroidal saponins: the shark-repelling pavoninins. Lipids 42:77–86PubMedCrossRefGoogle Scholar
  287. Wu JJ, Cheng KW, Zuo XF, Wang MF, Li P, Zhang LY, Wang H, Ye WC (2010) Steroidal saponins and ecdysterone from Asparagus filicinus and their cytotoxic activities. Steroids 75:734–739PubMedCrossRefGoogle Scholar
  288. Wu X, Wang L, Wang GC, Wang H, Dai Y, Ye WC, Li YL (2012a) New steroidal saponins and sterol glycosides from Paris polyphylla var. yunnanensis. Planta Med 78:1667–1675PubMedCrossRefGoogle Scholar
  289. Wu X, Wang L, Wang H, Dai Y, Ye WC, Li YL (2012b) Steroidal saponins from Paris polyphylla var. yunnanensis. Phytochemistry 81:133–143PubMedCrossRefGoogle Scholar
  290. Wu XH, Wang CZ, Zhang J, Wang SQ, Han L, Zhang YW, Yuan CS (2014a) Effects of smilaxchinoside A and smilaxchinoside C, two steroidal glycosides from Smilax riparia, on hyperuricemia in a mouse model. Phytother Res 28:1822–1828PubMedCrossRefGoogle Scholar
  291. Wu XH, Zhang J, Wang SQ, Yang VC, Anderson S, Zhang YW (2014b) Riparoside B and timosaponin J, two steroidal glycosides from Smilax riparia, resist to hyperuricemia based on URAT1 in hyperuricemic mice. Phytomedicine 21:1196–1201PubMedCrossRefGoogle Scholar
  292. Xiao X, Zou J, Bui-Nguyen TM, Bai P, Gao L, Liu J, Liu S, Xiao J, Chen X, Zhang X, Wang H (2012) Paris saponin II of Rhizoma Paridis—a novel inducer of apoptosis in human ovarian cancer cells. Biosci Trends 6:201–211PubMedCrossRefGoogle Scholar
  293. Xie BB, Liu HY, Ni W, Chen CX, Lü Y, Wu L, Zheng QT (2006) Five new steroidal compounds from Ypsilandra thibetica. Chem Biodivers 3:1211–1218PubMedCrossRefGoogle Scholar
  294. Xie BB, Liu HY, Ni W, Chen CX (2009) Ypsilandrosides C–G, five new spirostanol saponins from Ypsilandra thibetica. Steroids 74:950–955PubMedCrossRefGoogle Scholar
  295. Xie WL, Jiang R, Shen XL, Chen ZY, Deng XM (2015) Diosgenin attenuates hepatic stellate cell activation through transforming growth factor-β/Smad signaling pathway. Int J Clin Exp Med 8:20323–20329PubMedPubMedCentralGoogle Scholar
  296. Xing Z, Long Y, Lao F, He S, Liang N, Li B (2012) Effect of endophytic fungi on expression amount of key enzyme genes in saponins biosynthesis and Eleutherococcus senticosus saponins content. Zhongguo Zhong Yao Za Zhi 37:2041–2045PubMedGoogle Scholar
  297. Xu DP, Hu CY, Wei L, Pang ZJ (2007a) Isolation and structure determination of steroidal saponin from Dioscorea zingiberensis. Yao Xue Xue Bao 42:1162–1165PubMedGoogle Scholar
  298. Xu FQ, Zhong HM, Liu HY, Liu HQ, Chen CX (2007b) Steroidal saponins from Lysimachia Paridiformis. J Asian Nat Prod Res 9:493–497PubMedCrossRefGoogle Scholar
  299. Xu TH, Xu YJ, Xie SX, Zhao HF, Han D, Li Y, Niu JZ, Xu DM (2008) A novel steroidal glycoside, ophiofurospiside A from Ophiopogon japonicus (Thunb.) Ker-Gawl. J Asian Nat Prod Res 10:415–418PubMedCrossRefGoogle Scholar
  300. Xu DP, Hu CY, Wang L, Wang XC, Pang ZJ (2009a) Isolation and structure determination of steroidal saponin from Dioscorea zingiberensis. Yao Xue Xue Bao 44:56–59PubMedGoogle Scholar
  301. Xu DP, Hu CY, Zhang Y (2009b) Two new steroidal saponins from the rhizome of Polygonatum sibiricum. J Asian Nat Prod Res 11:1–6PubMedCrossRefGoogle Scholar
  302. Xu YJ, Xu TH, Liu Y, Xie SX, Si YS, Xu DM (2009c) Two new steroidal glucosides from Tribulus terrestris L. J Asian Nat Prod Res 11:548–553PubMedCrossRefGoogle Scholar
  303. Xu M, Zhang YJ, Li XC, Jacob MR, Yang CR (2010) Steroidal saponins from fresh stems of Dracaena angustifolia. J Nat Prod 73:1524–1528PubMedCrossRefGoogle Scholar
  304. Xu Y, Liu J, Liang L, Yang X, Zhang Z, Gao Z, Sui C, Wei J (2014) Molecular cloning and characterization of three cDNAs encoding 1-deoxy-d-xylulose-5-phosphate synthase in Aquilaria sinensis (Lour.) Gilg. Plant Physiol Biochem 82:133–141PubMedCrossRefGoogle Scholar
  305. Yada H, Kimura T, Suzuki M, Ohnishi-Kameyama M, Shinmoto H (2010) New steroidal saponin from Hosta sieboldiana. Biosci Biotechnol Biochem 74:861–864PubMedCrossRefGoogle Scholar
  306. Yan Y, Zhang JX, Liu KX, Huang T, Yan C, Huang LJ, Liu S, Mu SZ, Hao XJ (2014) Seco-pregnane steroidal glycosides from the roots of Cynanchum atratum and their anti-TMV activity. Fitoterapia 97:50–63PubMedCrossRefGoogle Scholar
  307. Yang QX, Yang CR (2006) Cytotoxic steroidal saponins from Polygonatum punctatum. Chem Biodivers 3:1349–1355PubMedCrossRefGoogle Scholar
  308. Yang SL, Liu XK, Wu H, Wang HB, Qing C (2009) Steroidal saponins and cytoxicity of the wild edible vegetable—Smilacina atropurpurea. Steroids 74:7–12PubMedCrossRefGoogle Scholar
  309. Yang J, Wang P, Wu W, Zhao Y, Idehen E, Sang S (2016) Steroidal saponins in oat bran. J Agric Food Chem 64:1549–1556PubMedCrossRefGoogle Scholar
  310. Ye Y, Chen F, Sun H, Li X, Xu S (2008) Stemucronatoside K, a novel C(21) steroidal glycoside from Stephanotis mucronata, inhibited the cellular and humoral immune response in mice. Int Immunopharmacol 8:1231–1238PubMedCrossRefGoogle Scholar
  311. Ye Y, Qu Y, Tang R, Cao S, Yang W, Xiang L, Qi J (2013) Three new neuritogenic steroidal saponins from Ophiopogon japonicus (Thunb.) Ker-Gawl. Steroids 78:1171–1176PubMedCrossRefGoogle Scholar
  312. Yen CT, Lee CL, Chang FR, Hwang TL, Yen HF, Chen CJ, Chen SL, Wu YC (2012) Indiosides G–K: steroidal glycosides with cytotoxic and anti-inflammatory activities from Solanum violaceum. J Nat Prod 75:636–643PubMedCrossRefGoogle Scholar
  313. Yen PH, Chi VT, Kiem PV, Tai BH, Quang TH, Nhiem NX, Anh HL, Ban NK, Thanh BV, Minh CV, Park S, Kim SH (2016) Spirostanol saponins from Tacca vietnamensis and their anti-inflammatory activity. Bioorg Med Chem Lett S0960–894:30533–30539Google Scholar
  314. Yin HX, Xue D, Bai N, Chen C, Chen Y, Zhang H (2008) Isolation and identification of major steroidal saponins of Paris polyphylla Smith var stenophylla Franch. Sichuan Da Xue Xue Bao Yi Xue Ban 39:485–488PubMedGoogle Scholar
  315. Yokosuka A, Mimaki Y (2009) Steroidal saponins from the whole plants of Agave utahensis and their cytotoxic activity. Phytochemistry 70:807–815PubMedCrossRefGoogle Scholar
  316. Yokosuka A, Jitsuno M, Yui S, Yamazaki M, Mimaki Y (2009) Steroidal glycosides from Agave utahensis and their cytotoxic activity. J Nat Prod 72:1399–1404PubMedCrossRefGoogle Scholar
  317. Yoon KD, Chin YW, Yang MH, Choi J, Kim J (2012) Application of high-speed countercurrent chromatography–evaporative light scattering detection for the separation of seven steroidal saponins from Dioscorea villosa. Phytochem Anal 23:462–468PubMedCrossRefGoogle Scholar
  318. Yu JQ, Deng AJ, Qin HL (2013) Nine new steroidal glycosides from the roots of Cynanchum stauntonii. Steroids 78:79–90PubMedCrossRefGoogle Scholar
  319. Yuan L, Ji TF, Li CJ, Wang AG, Yang JB, Su YL (2009) Two new steroidal saponins from the seeds of Allium cepa L. J Asian Nat Prod Res 11:213–218PubMedCrossRefGoogle Scholar
  320. Yuan JC, Zhang J, Wang FX, Pang X, Zhao Y, Xiong CQ, Ma BP (2014) New steroidal glycosides from the rhizome of Anemarrhena asphodeloides. J Asian Nat Prod Res 16:901–909PubMedCrossRefGoogle Scholar
  321. Yuan YL, Guo CR, Cui LL, Ruan SX, Zhang CF, Ji D, Yang ZL, Li F (2015) Timosaponin B-II ameliorates diabetic nephropathy via TXNIP, mTOR, and NF-κB signaling pathways in alloxan-induced mice. Drug Des Devel Ther 9:6247–6258PubMedPubMedCentralGoogle Scholar
  322. Zeng KW, Song FJ, Li N, Dong X, Jiang Y, Tu PF (2015) ASC, a bioactive steroidal saponin from Ophitopogin japonicas, inhibits angiogenesis through interruption of Src tyrosine kinase-dependent matrix metalloproteinase pathway. Basic Clin Pharmacol Toxicol 116:115–123PubMedCrossRefGoogle Scholar
  323. Zha L, Liu S, Su P, Yuan Y, Huang L (2016) Cloning, prokaryotic expression and functional analysis of squalene synthase (SQS) in Magnolia officinalis. Protein Expr Purif 120:28–34PubMedCrossRefGoogle Scholar
  324. Zhang Y, Li HZ, Zhang YJ, Jacob MR, Khan SI, Li XC, Yang CR (2006) Atropurosides A–G, new steroidal saponins from Smilacina atropurpurea. Steroids 71:712–719PubMedCrossRefGoogle Scholar
  325. Zhang Y, Zhang YJ, Jacob MR, Li XC, Yang CR (2008) Steroidal saponins from the stem of Yucca elephantipes. Phytochemistry 69:264–270PubMedCrossRefGoogle Scholar
  326. Zhang L, Liu JY, Xu LZ, Yang SL (2009a) Chantriolide C, a new withanolide glucoside and a new spirostanol saponin from the rhizomes of Tacca chantrieri. Chem Pharm Bull (Tokyo) 57:1126–1128CrossRefGoogle Scholar
  327. Zhang T, Liu H, Liu XT, Chen XQ, Wang Q (2009b) Steroidal saponins from the rhizomes of Paris delavayi. Steroids 74:809–813PubMedCrossRefGoogle Scholar
  328. Zhang LJ, Yu HS, Kang LP, Feng B, Quan B, Song XB, Ma BP, Kang TG (2012a) Two new steroidal saponins from the biotransformation product of the rhizomes of Dioscorea nipponica. J Asian Nat Prod Res 14:640–646PubMedCrossRefGoogle Scholar
  329. Zhang T, Kang LP, Yu HS, Liu YX, Zhao Y, Xiong CQ, Zhang J, Zou P, Song XB, Liu C, Ma BP (2012b) Steroidal saponins from the tuber of Ophiopogon japonicus. Steroids 77:1298–1305PubMedCrossRefGoogle Scholar
  330. Zhang C, Feng S, Zhang L, Ren Z (2013a) A new cytotoxic steroidal saponin from the rhizomes and roots of Smilax scobinicaulis. Nat Prod Res 27:1255–1260PubMedCrossRefGoogle Scholar
  331. Zhang J, Li H, Li H, Lu Z, Shi J, Xu Z (2013b) Screening and condition optimization of a strain for efficiently biotransformation of saponins in Dioscorea zingiberensis into diosgenin. Sheng Wu Gong Cheng Xue Bao 29:848–852PubMedGoogle Scholar
  332. Zhang R, Huang B, Du D, Guo X, Xin G, Xing Z, Liang Y, Chen Y, Chen Q, He Y, Huang W (2013c) Anti-thrombosis effect of diosgenyl saponins in vitro and in vivo. Steroids 78:1064–1070PubMedCrossRefGoogle Scholar
  333. Zhang H, Chen L, Kou JP, Zhu DN, Qi J, Yu BY (2014a) Steroidal sapogenins and glycosides from the fibrous roots of Polygonatum odoratum with inhibitory effect on tissue factor (TF) procoagulant activity. Steroids 89:1–10PubMedCrossRefGoogle Scholar
  334. Zhang L, Wang JT, Zhang DW, Zhang G, Guo SX (2014b) Molecular characterization of a HMG-CoA reductase gene from a rare and endangered medicinal plant, Dendrobium officinale. Yao Xue Xue Bao 49:411–418PubMedGoogle Scholar
  335. Zhang H, Su YF, Yang FY (2016a) Three new steroidal saponins from Helleborus thibetanus. Nat Prod Res 30:1724–1730PubMedCrossRefGoogle Scholar
  336. Zhang Y, Yang CR, Zhang YJ (2016b) Steroidal saponins from the rhizomes of Polygonatum prattii. J Asian Nat Prod Res 18:268–273PubMedCrossRefGoogle Scholar
  337. Zhao Y, Kang LP, Liu YX, Zhao Y, Xiong CQ, Ma BP, Dong FT (2007) Three new steroidal saponins from the rhizome of Paris polyphylla. Magn Reson Chem 45:739–744PubMedCrossRefGoogle Scholar
  338. Zhao Y, Kang LP, Liu YX, Liang YG, Tan DW, Yu ZY, Cong YW, Ma BP (2009) Steroidal saponins from the rhizome of Paris polyphylla and their cytotoxic activities. Planta Med 75:356–363PubMedCrossRefGoogle Scholar
  339. Zhao YJ, Chen X, Zhang M, Su P, Liu YJ, Tong YR, Wang XJ, Huang LQ, Gao W (2015) Molecular cloning and characterisation of farnesyl diphosphate synthase from Tripterygium wilfordii. PLoS ONE 10:e0125415PubMedPubMedCentralCrossRefGoogle Scholar
  340. Zhao H, Tang Q, Mo C, Bai L, Tu D, Ma X (2017) Cloning and characterization of squalene synthase and cycloartenol synthase from Siraitia grosvenorii. Acta Pharm Sin B 7:215–222PubMedCrossRefGoogle Scholar
  341. Zheng J, Zheng Y, Zhi H, Dai Y, Wang N, Wu L, Fan M, Fang Y, Zhao S, Zhang K (2013) Two new steroidal saponins from Selaginella uncinata (Desv.) spring and their protective effect against anoxia. Fitoterapia 88:25–30PubMedCrossRefGoogle Scholar
  342. Zheng L, Zhou Y, Zhang JY, Song M, Yuan Y, Xiao YJ, Xiang T (2014) Two new steroidal saponins from the rhizomes of Dioscorea zingiberensis. Chin J Nat Med 12:142–147PubMedGoogle Scholar
  343. Zhou LB, Chen DF (2008) Steroidal saponins from the roots of Asparagus filicinus. Steroids 73:83–87PubMedCrossRefGoogle Scholar
  344. Zhou X, He X, Wang G, Gao H, Zhou G, Ye W, Yao X (2006) Steroidal saponins from Solanum nigrum. J Nat Prod 69:1158–1163PubMedCrossRefGoogle Scholar
  345. Zhou LB, Chen TH, Bastow KF, Shibano M, Lee KH, Chen DF (2007) Filiasparosides A–D, cytotoxic steroidal saponins from the roots of Asparagus filicinus. J Nat Prod 70:1263–1267PubMedCrossRefGoogle Scholar
  346. Zhou ZL, Feng ZC, Fu CY, Zhang HL, Xia JM (2012) Steroidal and phenolic glycosides from the bulbs of Lilium pumilum DC and their potential Na +/K + ATPase inhibitory activity. Molecules 17:10494–10502PubMedCrossRefGoogle Scholar
  347. Zhu YL, Huang W, Ni JR, Liu W, Li H (2010) Production of diosgenin from Dioscorea zingiberensis tubers through enzymatic saccharification and microbial transformation. Appl Microbiol Biotechnol 85:1409–1416PubMedCrossRefGoogle Scholar
  348. Zhu L, Tan J, Wang B, Guan L, Liu Y, Zheng C (2011) In-vitro antitumor activity and antifungal activity of pennogenin steroidal saponins from Paris Polyphylla var. yunnanensis. Iran J Pharm Res 10:279–286PubMedPubMedCentralGoogle Scholar
  349. Zhu GL, Hao Q, Li RT, Li HZ (2014) Steroidal saponins from the roots of Asparagus cochinchinensis. Chin J Nat Med 12:213–217PubMedGoogle Scholar
  350. Zou K, Wang J, Du M, Li Q, Tu G (2006) A pair of diastereoisomeric steroidal saponins from cytotoxic extracts of Tupistra chinensis rhizomes. Chem Pharm Bull (Tokyo) 54:1440–1442CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Swati Upadhyay
    • 1
  • Gajendra Singh Jeena
    • 1
  • Shikha
    • 1
  • Rakesh Kumar Shukla
    • 1
  1. 1.Biotechnology Division (CSIR-CIMAP)Central Institute of Medicinal and Aromatic Plants, (CSIR-CIMAP) P.O. CIMAP (a laboratory under Council of Scientific and Industrial Research, India)LucknowIndia

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