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Secondary Metabolites from Turkish Astragalus Species

  • Derya GülcemalEmail author
  • Behnaz Aslanipour
  • Erdal BedirEmail author
Chapter

Abstracts

The genus Astragalus belonging to the Leguminosae family is a widely distributed plant throughout the temperate regions of the world. This plant species is used in various traditional and folklore medicines for the treatment of nephritis, diabetes, and uterine cancer and as antiperspirant, diuretic, and tonic. In Turkish folk medicine, the aqueous extracts of some Astragalus species are used to treat leukemia as well as for wound healing. The present chapter shall discuss about the secondary metabolites extracted from this plant species along with their uses in eradicating various ailments.

Keywords

Secondary metabolites Turkey Endemic species Turkish folk medicine Traditional medicine 

Introduction

The genus Astragalus belonging to the Leguminosae family is a widely distributed plant throughout the temperate regions of the world, located principally in Europe, Asia, and North America. It is represented in the flora of Turkey by 447 species, of which 224 are endemic (Davis 1970; Aytaç 2000). The roots of various Astragalus species represent very old and well-known drugs in traditional medicine for the treatment of nephritis, diabetes, and uterine cancer and as antiperspirant, diuretic, and tonic (Tang and Eisenbrand 1992). In Turkish folk medicine, the aqueous extracts of some Astragalus species are used to treat leukemia as well as for wound healing (Çalış et al. 1997; Bedir et al. 2000a).

Previous phytochemical studies on Turkish Astragalus species resulted in the isolation of a series of oleanane- and cycloartane-type triterpene saponins (Bedir et al. 1998a, b, 1999a, b, 2001a, b; Çalış et al. 1997, 2008a, b; Denizli et al. 2014; Djimtombaye et al. 2013; Gülcemal et al. 2011, 2012, 2013; Horo et al. 2010, 2012; Polat et al. 2009, 2010; Savran et al. 2012). Cycloartane- and oleanane-type glycosides from Astragalus species have shown interesting biological properties, including immunostimulating (Çalış et al. 1997; Bedir et al. 2000a; Yeşilada et al. 2005), antiprotozoal (Özipek et al. 2005), antiviral (Gariboldi et al. 1995), and cytotoxic activities (Tian et al. 2005).

Turkish Astragalus species have been studied extensively from phytochemistry and biological activity perspectives for the last 25 years. The following is a summary of these 25 years.

Phytochemistry and Biological Activity

Until now, 31 out of 447 Turkish Astragalus species, from 14 different sections, have been investigated for their secondary metabolite contents, and structures of 104 new triterpene saponins, 5 new phenolic glycosides, a new tryptophan derivative, and a new maltol glucoside were identified besides 63 known compounds.

Çalış et al. (1996) reported on the isolation and structural elucidation of four novel cycloartane-type triterpene glycosides, macrophyllosaponins A–D (1–4), from the roots of Astragalus oleifolius (Sect. Macrophyllium). By means of chemical (acetylation, alkaline hydrolysis) and spectroscopic methods (IR, 1D- and 2D-NMR, FABMS), their structures were established as 3-O-α-l-rhamnopyranosyl-24-O-(4″-O-acetyl)-β-d-xylopyranosyl-1α,3β,7β,24(S),-25-pentahydroxycycloartane (1), 3-O-α-l-rhamnopyranosyl-24-O-β-d-xylopyranosyl-1α,3β,7β,-24(S),25-pentahydroxycycloartane (2), 3-O-α-l-rhamnopyranosyl-25-O-β-d-glucoyranosyl-1α,3β,7β,24(S),25-pentahydroxycycloartane (3), and 3-O-α-l-rhamnopyranosyl-24-O-(2-O-β-d-xylopyranosyl)-β-d-xylopyranosyl-1α,3β,7β,24(S),25-pentahydroxycycloartane (4). According to the authors, the sapogenol moiety of these saponins was encountered for the first time in this study. The presence of hydroxyl groups at C-1 and C-7 positions of the sapogenol moiety are rare in Astragalus cycloartane chemistry as well as the absence of a hydroxyl group in ring D (Çalış et al. 1996).

Compound 1; C43H72O14; [α]20D −5.0° (c 0.28, MeOH); νKBrmax cm−1: 3400 (OH), 1735 (ester carbonyl); δC (CD3OD); FABMS m/z [M + Na]+ 835. Compound 2; C41H70O13; [α]20D +2.8° (c 0.58, MeOH); νKBrmax cm−1: 3400 (OH); δC (CD3OD); FABMS m/z [M + Na]+ 793. Compound 3; C42H72O14; [α]20D +15° (c 0.32, MeOH); νKBrmax cm−1: 3400 (OH); δC (CD3OD); FABMS m/z [M + Na]+ 823. Compound 4; C46H78O17; [α]20D −1.0° (c 0.32, MeOH); νKBrmax cm−1: 3400 (OH); δC (CD3OD); FABMS m/z [M + Na]+ 925. The structures and 13C NMR data of the aglycone moiety of 1 are provided below together with sugar residues identified for compounds 14.

Calis et al. isolated eight known saponins: astrasieversianins II (Gan et al. 1986) and X (Gan et al. 1986); astragalosides I (Kitagawa et al. 1983a), II (Kitagawa et al. 1983a), IV (Kitagawa et al. 1983a), and VI (Kitagawa et al. 1983b); and cyclocanthosides E (Isaev et al. 1992) and G (Isaev et al. 1992) from the roots of Astragalus melanophrurius (Sect. Christiana). The metabolites were examined for their bioactivities; referring to the results, they were found to have modest antibiotic activity toward Escherichia coli, Bacillus subtilis, and Micrococcus luteus. On the other hand, all compounds exhibited immunomodulatory activity via stimulation of human lymphocyte proliferation in the concentration range of 0.01–10 μg/mL (Çalış et al. 1997).

A novel cycloartane-type glycoside, cyclocephaloside I (5), was reported from the roots of Astragalus microcephalus in addition to known glycosides: cyclocanthoside E (Isaev et al. 1992) and astragaloside IV (Kitagawa et al. 1983a). The structure of 5 was elucidated on the basis of spectral (IR, 1H and 13C NMR, and FABMS) and chemical (acetylation) methods and established as 20,25-epoxy-3β-(β-d-xylopyranosyl)oxy-6α-(β-d-glucopyranosyl)oxy-cycloartane-16β,24α-diol (Bedir et al. 1998a).

Compound 5; C41H68O14; [α]20D +6.1° (c 0.42, MeOH); νKBrmax cm−1: (KBr) 3400 (OH); δC (C5D5N); FABMS m/z [M + Na]+ 807. The structure and 13C chemical shifts are given below for compound 5.

In 1998, a report described three new cycloartane-type triterpene glycosides, brachyosides A (6), B (8), and C (7), from the roots of Astragalus brachypterus (Sect. Pterophorus) and one new glycoside, cyclocephaloside II (9), from the roots of Astragalus microcephalus (Sect. Rhacophorus) together with five known saponins, astragalosides I (Kitagawa et al. 1983a), II (Kitagawa et al. 1983a), and IV (Kitagawa et al. 1983a), cyclocanthoside E (Isaev et al. 1992), and cycloastragenol (Kitagawa et al. 1983a). The structures of the new compounds were established by detailed spectral analysis, as 3-O-[β-d-xylopyranosyl(1→3)-β-d-xylopyranosyl-6-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (6), 3-O-β-d-xylopyranosyl-6-O-β-d-glucopyranosyl-24-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (7), 20(R),24(S)-epoxy-6-O-β-d-glucopyranosyl-3β,6α,16β,25-tetrahydroxycycloartane (8), and 20(R),24(S)-epoxy-3-O-(4′-O-acetyl)-β-d-xylopyranosyl-6-O-β-d-glucopyranosyl-3β,6α,16β,25-tetrahydroxycycloartane (9) (Bedir et al. 1998b).

Compound 6; C46H78O18; [α]25D +15.5° (c 0.1, MeOH); δC (CD3OD); FABMS m/z [M–H] 917. Compound 7; C47H80O19; [α]25D +12.5° (c 0.1, MeOH); δC (CD3OD); FABMS m/z [M–H] 947. Compound 8; C36H60O10; [α]25D +40.1° (c 0.1, MeOH); δC (CD3OD); FABMS m/z [M–H] 651. Compound 9; C43H70O15; [α]25D +19.6° (c 0.1, MeOH); δC (CD3OD); FABMS m/z [M–H] 825.

The structures and 13C NMR data of the aglycone moieties of 6 and 9 are provided below together with sugar residues determined for compounds 69.

In 1999, a new tridesmosidic cycloartane-type glycoside cephalotoside A (10) was isolated from the roots of Astragalus cephalotes var. brevicalyx (Sect. Rhacophorus) in addition to the known glycosides cyclocanthosides A (Fadeev et al. 1988), D (Isaev et al. 1992), and E (Isaev et al. 1992). The structure of the new compound was established on the basis of spectral data and chemical (acetylation) methods as 3β-(β-d-xylopyranosyl)oxy-16β-(β-d-glucopyranosyl)oxy-24-(β-d-xylopyranosyl)oxy-cycloartane-6α,25-diol (Çalış et al. 1999).

Compound 10; C46H78O18; [α]20D +20.9° (c 0.53, MeOH); νKBrmax cm−1: (KBr) 3400 (OH), 2927 (CH), 1170 and 1044 (C–O–C); δC (C5D5N); FABMS m/z [M + Na]+ 941. The structure and 13C chemical shifts of compound 10 are presented below.

The study of the chemical constituents of Astragalus trojanus roots (Sect. Pterophorus) resulted in the isolation of six novel cycloartane-type glycosides (1116). In addition, a new oleanane glycoside (17) and a new tryptophan derivative (18) were also isolated and characterized. MS, IR, 1H NMR, and 13C NMR experiments established the structures of compounds 11–17 as 3-O-β-d-xylopyranosyl-6-O-β-d-glucopyranosyl-16-O-acetoxy-(20R,24S)-epoxy-3β,6α,25-trihydroxycycloartane (trojanoside A), 3-O-β-d-xylopyranosyl-6-O-β-d-xylopyranosyl-25-O-β-d-glucopyranosyl-(20R,24S)-epoxy-3β,6α,16β,25-tetrahydroxycycloartane (trojanoside B), 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranosyl]-24-O-β-d-glucopyranosyl-3β,6α,16β,(24S),25-pentahydroxycycloartane (trojanoside C), 3-O-β-d-glucopyranosyl-6-O-β-d-glucopyranosyl-24-O-β-d-glucopyranosyl-3β,6α,16β,(24S),25-pentahydroxycycloartane (trojanoside D), 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranosyl]-6-O-β-d-glucopyranosyl-24-O-β-d-glucopyranosyl-3β,6α,16β,(24S),25-pentahydroxycycloartane (trojanoside E), 3-O-[α-l-arabinopyranosyl-(1→2)-β-d-xylopyranosyl]-6-O-β-d-glucopyranosyl-24-O-β-d-glucopyranosyl-3β,6α,16β,(24S),25-pentahydroxycycloartane (trojanoside F), and 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranosyl-(1→2)-β-d-glucuronopyranosyl]-29-O-β-d-glucopyranosyl-3β,22β,24,29-tetrahydroxyolean-12-en (astrojanoside A), respectively. The structure of compound 18, named as achillamide trivially, was determined as N-[3-hydroxy-3-methyl-glutaroyl]-tryptophan (Bedir et al. 1999a). Besides, the known compounds astrasieversianin I (Gan et al. 1986), astrasieversianin II (Gan et al. 1986), astragaloside I (Kitagawa et al. 1983a), astragaloside IV (Kitagawa et al. 1983a), astragaloside VII (Kitagawa et al. 1983c), and brachyoside C (Bedir et al. 1998b) were also purified and identified from the roots of A. trojanus. According to the authors, tetraglycosidic-type cycloartanes such as trojanosides E and F were isolated from Astragalus genus for the first time (Bedir et al. 1999a).

Compound 11; C43H70O15; [α]25D +20.1° (c 0.1, MeOH); νKBrmax cm−1: 3420 (OH), 1735 (ester carbonyl), 1260 and 1049 (C–O–C); δC (CD3OD); FABMS m/z [M–H] 825. Compound 12; C46H76O18; [α]25D +13.2° (c 0.1, MeOH); νKBrmax cm−1: 3420 (OH), 1270 and 1040 (C–O–C); δC (CD3OD); FABMS m/z [M–H] 915. Compound 13; C47H80O18; [α]25D −5.0° (c 0.1, MeOH); νKBrmax cm−1: 3420 (OH), 2933 (CH), 1250 and 1024 (C–O–C); δC (CD3OD); FABMS m/z [M–H] 931. Compound 14; C48H82O20; [α]25D +22.5° (c 0.1, MeOH); νKBrmax cm−1: 3392 (OH), 2935 (CH), 1257 and 1044 (C–O–C); δC (CD3OD); FABMS m/z [M–H] 977. Compound 15; C53H90O23; [α]25D +2.6° (c 0.1, MeOH); νKBrmax cm−1: 3392 (OH), 2933 (CH), 1257 and 1044 (C–O–C) cm−1; δC (CD3OD); FABMS m/z [M–H] 1093. Compound 16; C52H88O23; [α]25D +5.2° (c 0.1, MeOH); νKBrmax cm−1: 3420 (OH), 2924 (CH), 1270 and 1040 (C–O–C); δC (CD3OD); FABMS m/z [M–H] 1079. Compound 17; C53H86O23; [α]25D +16.7° (c 0.1, MeOH); νKBrmax cm−1: 3393 (OH), 2926 (CH), 1749 (C=O), 1636 (C=C), 1271 and 1045 (C–O–C); δC (CD3OD); FABMS m/z [M–H] 1089. Compound 18; C17H20O6N2; [α]25D −29.0° (c 0.1, MeOH); νKBrmax cm−1: 3500 (NH), 3392 (OH), 1748, 1733, 1683 (CO-NH, C=O); δC (CD3OD); FABMS m/z [M–H] 347. The structures and 13C NMR data of compounds 1118 are provided below.

Isolation of trojanoside H (19) was also reported from the aerial parts of Astragalus trojanus along with six known glycosides astragaloside II (Kitagawa et al. 1983a), astragaloside IV (Kitagawa et al. 1983a), astragaloside VII (Bedir et al. 1999a), brachyoside B (Bedir et al. 1998b), brachyoside C (Bedir et al. 1998b), and the pterocarpan derivative maackiain (Chaudhuri et al. 1995). The structure of trojanoside H was confirmed by spectral methods (1-D and 2-D NMR and FABMS) and established as 3-O-β-[α-l-arabinopyranosyl-(1→2)-β-d-xylopyranosyl]-6-O-β-d-glucopyranosyl-20(R),24(S)-epoxy-3β,6α,16β,25-tetrahydroxycycloartane (Bedir et al. 1999b).

Compound 19; C46H76O18; [α]25D +14.2°; δC (CD3OD); FABMS m/z [M–H] 915. The 13C chemical shifts are given below for compound 19.

Another series of cycloartane saponins, trojanosides I–K (20, 21, and 22), were also isolated from the aerial parts of Astragalus trojanus. The structures of three new saponins were established as 3-O-β-(2′,3′-di-O-acetyl)-d-xylopyranosyl-6-O-β-d-glucopyranosyl-16-O-acetoxy-20(R),24(S)-epoxycycloartane-3β,6α,16β, 25-tetrol (20), 3-O-[α-l-rhamnopyranosyl-(1→2)-β-(3′,4′-di-O-acetyl)-d-xylopyranosyl]-6-O-β-d-xylopyranosyl-20(R),24(S)-epoxycycloartane-3β,6α,16β,25-tetrol (21), and 3-O-β-d-xylopyranosyl-6,16-di-O-β-d-glucopyranosyl-20(R),24(S)-epoxycycloartane-3β,6α,16β,25-tetrol (22) (Bedir et al. 2001a). Astrasieversianin I (Gan et al. 1986), astrasieversianin II (Gan et al. 1986), astrasieversianin XV (Gan et al. 1986), astragaloside I (Kitagawa et al. 1983a), astragaloside II (Kitagawa et al. 1983a), astragaloside IV (Kitagawa et al. 1983a), astragaloside VII (Kitagawa et al. 1983c), and trojanoside H (Bedir et al. 1999b) were also isolated and identified on the basis of their HR-ESI-MS and NMR (1H– and 13C–) data, in comparison with literature values (Bedir et al. 2001a).

Compound 20; C47H74O17; νKBrmax cm−1: 3419, 2936, 1726, 1461, 1379, 1262, 1078 and 1041; δC (C5D5N); HR-ESI-MS at m/z [M + Na]+ 933.3207. Compound 21; C50H80O19; νKBrmax cm−1: 3408, 2928, 1745, 1371, 1244 and 1042; δC (C5D5N); HR-ESI-MS at m/z [M + Na]+ 1007.3524. Compound 22; C48H78O18; νKBrmax cm−1: 3395, 2934, 1726, 1461, 1373, 1262 and 1057; δC (C5D5N); HR-ESI-MS at m/z [M + Na]+ 965.5188. The structures and 13C NMR data of the compounds (2022) are shown below.

Bedir et al. reported on the isolation and characterization of a new flavonol glycoside, isorhamnetin 3-O-β-d-apiofuranosyl-(1→2)-[α-l-rhamnopyranosyl-(1→6)]-β-d-galactopyranoside (23), and a known glycoside, isorhamnetin 3-O-α-l-rhamnopyranosyl-(1→6)-β-d-galactopyranoside (Burasheva et al. 1975), from the aerial parts of Astragalus vulneraria (Sect. Vulneraria) (Bedir et al. 2000b).

Compound 23; [α]25D +38.4° (c 0.1, MeOH); δC (CD3OD); FABMS m/z [M–H] 755. The structure and 13C chemical shifts are given below for compound 23.

The same year, macrophyllosaponin E (24), a novel cycloartane-type triterpene, has been isolated from the roots of Astragalus oleifolius (Bedir et al. 2000c).The structure and 13C chemical shifts are provided below for compound 24.

Compound 24; C42H72O15; δC (CD3OD); HR-ESI-FT-MS at m/z [M + Na]+ 839.4721.

In 2001, Bedir et al. reported on the isolation and structural elucidation of two novel cycloartane-type glycosides, 16-O-β-d-glucopyranosyl-20(S),24(R)-5α-9-diepoxy-2α,3β,16β,25-tetrahydroxy-9,10-seco-cycloarta-1(10),6(7)-diene (25) and 3-O-β-d-xylopyranosyl-16-O-β-d-glucopyranosyl-20(S),24(R)-epoxy-3β,16β,25-trithydroxycycloartane (26) from the roots of Astragalus prusianus. In the paper, a unique 5-α-9-epoxy structural feature in 25 was reported that was encountered for the first time for triterpene chemistry in nature (Bedir et al. 2001b).

Compound 25; C36H56O11; [α]25D −112.5° (c 0.004, MeOH); νKBrmax cm−1: 3396, 2927, 2395, 2358, 2339, 1738, 1593, 1382, 1256, 1165, 1073 and 1032; δC (CD3OD); HR-ESI-FT-MS m/z [M + Na]+ 687.2429. Compound 26; C41H68O13; [α]25D +20.0° (c 0.004, MeOH); νKBrmax cm−1: 3376, 2933, 2870, 2363, 1726, 1459, 1381, 1166, 1071 and 1045; δC (C5D5N); HR-ESI-FT-MS m/z [M + Na]+ 791.4842. The structures and 13C chemical shifts are presented below for compounds 25 and 26.

In another study in 2001, four new phenolic glycosides, β-apiofuranosyl-(1→2)-β-glucopyranosides (2730), along with the new cycloartane triterpenes 20(R),25-epoxy-3α,6β,16α,24β-tetrahydroxycycloartane (31) and 20(R),24(S)-epoxy-3β,6α,25-trihydroxycycloartan-16-one (32) were isolated and purified from the roots of Astragalus zahlbruckneri (Sect. Rhacophorus). Structures of the new compounds were established as (+)-neo-olivil 4-O-β-apiofuranosyl-(1→2)-β-glucopyranoside (27), 7,8-dihydro-7-hydroxyconiferyl alcohol 4-O-β-apiofuranosyl-(1→2)-β-glucopyranoside (28), 2-methoxyphenol-4-O-β-apiofuranosyl-(1→2)-β-glucopyranoside (29), 3-hydroxy-5-methoxyphenol-2-O-β-apiofuranosyl-(1→2)-β-glucopyranoside (30), 20(R),25-epoxy-3β,6α,16β,24α-tetrahydroxycycloartane (31), and 20(R),24(S)-epoxy-3β,6α,25-trihydroxycycloartan-16-one (32). Additionally, a known cycloartane sapogenin, namely, cycloastragenol (Kitagawa et al. 1983a), was isolated from the apolar fraction of A. zahlbruckneri. Compound 32 was reported before as a cycloartane derivative obtained by chemical oxidation of cycloastragenol (Kitagawa et al. 1983a, b, d). The structures were elucidated by a combination of spectroscopic data (1H NMR, 13C NMR, HMBC, HMQC, MS, and IR) (Çalış et al. 2001).

Compound 27; C31H42O16; [α]25D −69.9° (c 0.5, MeOH); δC (CD3OD); FABMS m/z [M–H] 669. Compound 28; [α]25D −56.0 (c 0.5, MeOH); δC (CD3OD); FABMS m/z [M–H] 491. Compound 29; [α]25D −59.0° (c 0.5, MeOH); δC (CD3OD); FABMS m/z [M–H] 433. Compound 30; [α]25D −40.5° (c 0.5, MeOH); δC (CD3OD); FABMS m/z [M–H] 449. Compound 31; C30H50O5; [α]25D +23.3° (c 0.5, CHCl3); δC (CDCl3); FABMS m/z [M–H] 489. Compound 32; C30H48O5; [α]25D +10.0° (c 0.5, CHCl3); δC (CDCl3); FABMS m/z [M–H] 487. The structures and 13C chemical shifts of compounds 27–32 are shown below.

Another phytochemical investigation was published in 2005, and two new cycloartane-type glycosides oleifoliosides A (33) and B (34) were isolated from the lower stem parts of Astragalus oleifolius . Structures of the new compounds were established as 3-O-[β-xylopyranosyl-(1→2)-α-arabinopyranosyl]-6-O–β-xylopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane and 3-O-[β-xylopyranosyl-(1→2)-α-arabinopyranosyl]-6-O–β-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane, by using 1D- and 2D-NMR techniques and mass spectrometry. Additionally, three known cycloartane glycosides cyclocanthoside E (Isaev et al. 1992), astragaloside II (Kitagawa et al. 1983a), and astragaloside IV (Kitagawa et al. 1983a) were also isolated and characterized. These compounds were tested for their cytotoxicities on primary mammalian (L6) cells along with in vitro antiplasmodial, leishmanicidal, and trypanocidal activities. All the compounds showed good growth inhibitory activity opposed to Leishmania donovani with IC50 values ranging from 13.2 to 21.3 μg/mL. While all compounds were inactivite against Trypanosoma cruzi and Plasmodium falciparum, only two known compounds, namely, astragaloside II (IC50 66.6 μg/mL) and cyclocanthoside E (IC50 85.2 μg/mL), showed weak activity against Trypanosoma brucei rhodesiense. None of the compounds had toxicity to mammalian cells (IC50’s > 90 μg/mL). In this study, leishmanicidal and trypanocidal activities of cycloartane-type triterpene glycosides were reported for the first time (Özipek et al. 2005).

Compound 33; C45H76O17; [α]27D +18.9° (c 0.1, MeOH); νKBrmax cm−1: 3427 (OH), 2922 (CH), 1048; δC (C5D5N); ESI-MS m/z [M + Na]+ 911. Compound 34; C46H78O18; [α]27D +21.9° (c 0.1, MeOH); νKBrmax cm−1: 3423 (OH), 2923 (CH), 1167, 1078; δC (C5D5N); ESI-MS m/z [M + Na]+ 941. The structures and 13C NMR data of the compounds (3334) are presented below.

In 2005, a study was performed on another Turkish species; Astragalus gilvus (Sect. Christiana) and known cycloartane-type saponins, astrasieversianins I (Gan et al. 1986), II (Gan et al. 1986), VI (Gan et al. 1986), VIII (Gan et al. 1986), and X (Gan et al. 1986) and astragaloside IV (Kitagawa et al. 1983a), were isolated. As in Astragalus gilvus , the other studied species of Christiana section, viz., Astragalus melanophrurius, was also rich in acetylated sugar residues attached to cycloartane nucleus. Thus the authors made a comment about the probable chemotaxonomic significance of the acetylated compounds for Christiana section, implying overexpression of acetyl transferase genes in the plants of this section (Tabanca et al. 2005).

A new cycloartane-type triterpene glycoside, namely, (20R,24S)-3-O-[β-d-apiofuranosyl-(1→2)-β-d-xylopyranosyl]-6-O-β-d-glucopyranosyl-,6α,16β,25-tetrahydroxy-20,24-epoxycycloartane, named baibutoside (35), was isolated from the roots of Astragalus baibutensis (Sect. Pterophorus) along with four known glycosides, acetylastragaloside I (Kitagawa et al. 1983a) and astragalosides I (Kitagawa et al. 1983a), II (Kitagawa et al. 1983a), and IV (Kitagawa et al. 1983a). The authors commented that the apiose unit in cycloartane glycosides as in baibutoside was a very unusual finding. The evaluation of antiprotozoal activities of all the compounds on a panel of parasites including Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani, and Plasmodium falciparum was also studied. The selective cytotoxicity tests versus primary L6 mammalian cells (rat skeletal myoblasts) revealed toxicity only for acetylastragaloside I with narrow selectivity index values of 2.5 and 4.8. Moreover, the compounds had no activity against L. donovani and P. falciparum. Almost all purified metabolites, except baibutoside, showed some growth inhibitory effect on T. brucei rhodesiense; among all, acetylastragaloside I was reported as the most active compound with IC50 value of 9.5 μg/mL. On the other hand, acetylastragaloside I also showed significant activity against T. cruzi (IC50 value of 5.0 μg/mL). Antiprotozoal activity of the cycloartane-type glycosides was reported for the first time in this study (Çalış et al. 2006).

Compound 35; C46H76O18; [α]20D −7.0° (c 0.1, MeOH); νKBrmax cm−1: 3400 (OH), 2933 (CH), 1166, 1077, 1042; δC (C5D5N); ESI-MS m/z [M + Na]+ 939.6. The structure and 13C chemical shifts are provided below for compound 35.

A new monodesmosidic cycloartane-type glycoside together with two known cycloartane-type glycosides was obtained from Astragalus elongatus (Sect. Proselius) and was identified as elongatoside (3-O-[α-arabinopyranosyl-(1→2)-β-xylopyranosyl]-cycloastragenol) (36), askendosides D (3-O-[α-arabinopyranosyl-(1→2)-β-xylopyranosyl]-6-O-β-xylopyranosyl-cycloastragenol) (Isaev et al. 1983a), and G (3-O-[α-arabinopyranosyl-(1→2)-β-xylopyranosyl]-16-O-β-glucopyranosyl-3β,6α,16β,24(R),25-pentahydroxycycloartane) (Isaev 1996), on the basis of NMR experiments and mass spectrometry. For all pure compounds, human microvascular endothelial cell line (HMEC-1) was used to measure the inhibition of proliferation and ICAM-1 expression in vitro. Compound 36 was reported to possess weak activity in the ICAM-1 assay (Çalış et al. 2008a).

Compound 36; C40H66O13; [α]31D +31.0° (c 0.1, MeOH); δC (CD3OD); HR-FAB-MS m/z [M + H]+ 755.4564 (calcd. for C40H67O13 755.4582 [M + H]+). The structure and 13C chemical shifts are shown below for compound 36.

Avunduk et al. (2008) reported on the isolation and structural elucidation of six new triterpene saponins, 3-O-α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranosyl-(1→2)-β-d-glucuronopyranosyl-21-epi-kudzusapogenol A (37), 3-O-α-l-rhamnopyranosyl-(1→2)-β-d-glucopyranosyl-(1→2)-β-d-glucuronopyranosyl-21-epi-kudzusapogenol A (38), 3-O-α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranosyl-(1→2)-β-d-glucuronopyranosyl-22-O-β-d-glucopyranosyl-21-epi-kudzusapogenol A (39), 3-O-α-l-rhamnopyranosyl-(1→2)-β-d-glucopyranosyl-(1→2)-β-d-glucuronopyranosyl-22-O-β-d-glucopyranosyl-21-epi-kudzusapogenol A (40), 3-O-α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranosyl-(1→2)-β-d-glucuronopyranosyl-22-O-α-l-arabinopyranosyl-21-epi-kudzusapogenol A (41), and 3-O-α-l-rhamnopyranosyl-(1→2)-β-d-glucopyranosyl-(1→2)-β-d-glucuronopyranosyl-22-O-α-l-arabinopyranosyl-21-epi-kudzusapogenol A (42), from the roots of Astragalus flavescens (Sect. Eustales) (Avunduk et al. 2008) together with five known compounds named trojanoside B (Bedir et al. 1999a), azukisaponin V (Kitagawa et al. 1983e), and astragalosides IV (Kitagawa et al. 1983a), VII (Kitagawa et al. 1983c), and VIII (Kitagawa et al. 1983c).

Compound 37; C47H76O19; [α]25D −8.0° (c 0.05, MeOH); δC (C5D5N); HR-ESI-MS m/z [M + Na]+ 967.4884 (calcd. 967.4879). Compound 38; C48H78O20; [α]25D −7.5° (c 0.05, MeOH); δC (C5D5N); HR-ESI-MS m/z [M + Na]+ 997.4980 (calcd. 997.4984). Compound 39; C53H86O24; [α]25D −6.2° (c 0.05, MeOH); δC (C5D5N); HR-ESI-MS m/z [M + Na]+ 1129.5402 (calcd. 1129.5407). Compound 40; C54H88O25; [α]25D −4.5° (c 0.05, MeOH); δC (C5D5N); HR-ESI-MS m/z [M + Na]+ 1159.5508 (calcd. 1159.5512). Compound 41; C52H84O23; [α]25D +3.1° (c 0.05, MeOH); δC (C5D5N); HR-ESI-MS m/z [M + Na]+ 1099.5295 (calcd. 1099.5301). Compound 42; C53H86O24; [α]25D +8.5° (c 0.05, MeOH); δC (C5D5N); HR-ESI-MS m/z [M + Na]+ 1129.5409 (calcd. 1129.5407). The structures and carbon NMR data of the compounds are provided below (37–42).

Another phytochemical work was performed in 2008. In this research, four new cycloartane glycosides, including 3-O-[α-l-arabinopyranosyl-(1→2)-β-d-xylopyranosyl]-3β,6α,16β,23α,25-pentahydroxy-20(R),24(S)-epoxycycloartane (43), 3-O-[α-l-arabinopyranosyl-(1→2)-β-d-xylopyranosyl]-16-O-hydroxyacetoxy-23-O-acetoxy-3β,6α,25-trihydroxy-20(R),24(S)-epoxycycloartane (44), 3-O-[α-l-arabinopyranosyl-(1→2)-β-d-xylopyranosyl]-25-O-β-d-glucopyranosyl-3β,6α,16β,25-tetrahydroxy-20(R),24(S)-epoxycycloartane (45), and 3-O-[α-l-arabinopyranosyl-(1→2)-β-d-xylopyranosyl]-3β,6α,23α,25-tetrahydroxy-20(R),24(R)-16β,24;20,24-diepoxycycloartane (46), along with three known cycloartane glycosides, 3-O-[α-l-arabinopyranosyl-(1→2)-β-d-xylopyranosyl]-3β,6α,16β,25-tetrahydroxy-20(R),24(S)-epoxycycloartane (Isaev et al. 1983a), askendoside C (Isaev et al. 1983b), and askendoside G (Isaev 1996), were isolated from the MeOH extract of the roots of Astragalus campylosema ssp. campylosema (Sect. Hololeuce). Their structures were established by the extensive use of 1D- and 2D-NMR experiments along with ESIMS and HRMS analysis. The authors commented that the presence of the hydroxyl function at position 23 (4344) and the ketalic function at C-24 (46) were very rare in the cycloartane-type triterpene class (Çalış et al. 2008b).

Compound 43; C40H66O14; [α]35D +40.0° (c 0.1, MeOH); νKBrmax cm−1: 3472 (>OH), 3035 (cyclopropane ring), 2932 (>CH), 1273 and 1040 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 793.4355 (calcd. for C40H66O14Na, 793.4350). Compound 44; C44H70O17; [α]35D +67.0° (c 0.1, MeOH); νKBrmax cm−1: 3480 (>OH), 3044 (cyclopropane ring), 2928 (>CH), 1734 (C=O), 1277-1035 (C–O–C);δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 893.4519 (calcd. for C44H70O17Na, 893.4511). Compound 45; C46H76O18; [α]35D +24.0° (c 0.1, MeOH); νKBrmax cm−1: 3475 (>OH), 3047 (cyclopropane ring), 2925 (>CH), 1270-1043 (C–O–C); HR-MALDITOF-MS m/z [M + Na]+ 939.4934 (calcd. for C46H76O18Na, 939.4929). Compound 46; C40H64O14; [α]35D +20.0° (c 0.1, MeOH); νKBrmax cm−1: 3470 (>OH), 3040 (cyclopropane ring), 2930 (>CH), 1280-1045 (C–O–C); HR-MALDITOF-MS m/z [M + Na]+ 791.4199 (calcd. for C40H64O14Na, 791.4194). The structures and 13C chemical shifts are presented below for compounds 43–46.

In 2009, on the basis of extensive spectroscopic analysis (IR, HR-MALDITOF-MS, 1H NMR, 13C NMR, HSQC, and HMBC), Polat et al. reported on the isolation and structural elucidation of five new cycloartane-type triterpene glycosides from the methanolic extract of the roots of Astragalus amblolepis Fischer (Sect. Rhacophorus) along with one known saponin, 3-O-β-d-xylopyranosyl-16-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (Karimov et al. 1998). Structures of the new compounds were established as 3-O-β-d-xylopyranosyl-25-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (47), 3-O-[β-d-glucuronopyranosyl-(1→2)-β-d-xylopyranosyl]-25-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (48), 3-O-β-d-xylopyranosyl-24,25-di-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (49), 6-O-α-l-rhamnopyranosyl-16,24-di-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (50), and 6-O-α-l-rhamnopyranosyl-16,25-di-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (51). The authors commented that the absence of sugar residue at C-3 position of cycloartane glycosides such as compounds 50 and 51 was rather unusual in nature. Moreover, a rhamnosyl moiety at C-6 position was reported for the first time in cyclocanthogenol skeleton, one of the most common aglycones in Astragalus genus together with cycloastragenol. In this study, the presence of glucuronic acid moiety was reported for the first time in cycloartane chemistry (Polat et al. 2009).

Compound 47; C41H70O14; [α]25D +34.0° (c 0.1, MeOH); νKBrmax cm−1: 3480 (>OH), 3025 (cyclopropane ring), 2870 (>CH), 1290-1030 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 809.4669 (calcd. for C41H70O14Na, 809.4663). Compound 48; C47H78O20; [α]25D +15.8° (c 0.1, MeOH); νKBrmax cm−1: 3477 (>OH), 3048 (cyclopropane ring), 2895 (>CH), 1285-1043 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 985.4979 (calcd. for C47H78O20Na, 985.4984). Compound 49; C47H80O19; [α]25D +22.7° (c 0.1, MeOH); νKBrmax cm−1: 3483 (>OH), 3027 (cyclopropane ring), 2877 (>CH), 1279-1038 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 971.5199 (calcd. for C47H80O19Na, 971.5192). Compound 50; C48H82O19; [α]25D +17.9° (c 0.1, MeOH); νKBrmax cm−1: 3472 (>OH), 3040 (cyclopropane ring), 2883 (>CH), 1283-1029 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 985.5350 (calcd. for C48H82O19Na, 985.5348). Compound 51; C48H82O19; [α]25D +24.4° (c 0.1, MeOH); νKBrmax cm−1: 3486 (>OH), 3035 (cyclopropane ring), 2874 (>CH), 1292-1040 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 985.5341 (calcd. for C48H82O19Na, 985.5348). The structures and carbon NMR data of compounds 4751 were provided below.

Three new cycloartane-type triterpene glycosides were reported from Astragalus wiedemannianus (Sect. Pterophorus) in addition to known secondary metabolites, namely, cycloastragenol (Kitagawa et al. 1983a), cycloascauloside B (Alaniya et al. 2008), astragaloside IV (Kitagawa et al. 1983a), astragaloside VIII (Kitagawa et al. 1983c), brachyoside B (Bedir et al. 1998b), astragaloside II (Kitagawa et al. 1983c), astrachrysoside A (Wang et al. 1990), and astrasieversianin X (Gan et al. 1986). The structures of the new compounds were elucidated on the basis of 1D- and 2D-NMR techniques and established as 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-glucopyranosyl]-25-O-β-d-glucopyranosyl-20(R),24(S)-epoxy-3β,6α,16β,25-tetrahydroxycycloartane (52), 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranosyl]-6-O-β-d-glucopyranosyl-24-O-α-(4′-O-acetoxy)-l-arabinopyranosyl-16-O-acetoxy-3β,6α,16β,24(S),25-pentahydroxycycloartane (53), and 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranosyl]-6-O-β-d-glucopyranosyl-24-O-α-l-arabinopyranosyl-16-O-acetoxy-3β,6α,16β,24(S),25-pentahydroxycycloartane (54). In this study, the presence of an arabinose moiety on the acyclic side chain of cycloartanes was encountered for the first time (Polat et al. 2010).

Compound 52; C48H80O19; [α]25D +25.2° (c 0.1, MeOH); νKBrmax cm−1: 3474 (>OH), 3042 (cyclopropane ring), 2934 (>CH), 1271-1024 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 983.5196 (calcd. for C48H80O19Na, 983.5192). Compound 53; C56H92O24; [α]25D +35.8° (c 0.1, MeOH); νKBrmax cm−1: 3481 (>OH), 3035 (cyclopropane ring), 2941 (>CH), 1737 (C=O), 1264-1038 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 1171.5880 (calcd. for C56H92O24Na, 1171.5876). Compound 54; C54H90O23; [α]25D +38.7° (c 0.1, MeOH); νKBrmax cm−1: 3486 (>OH), 3047 (cyclopropane ring), 2930 (>CH), 1728 (C=O), 1260-1031 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 1129.5778 (calcd. for C54H90O23Na, 1129.5771). The structures and 13C NMR data of 5254 are shown below.

In 2010, a report described six new cycloartane-type triterpene glycosides from Astragalus icmadophilus (Sect. Acanthophace) along with two known cycloartane-type glycosides, five known oleanane-type triterpene glycosides, and one known flavonol glycoside. The structures of the new compounds were established by detailed spectral analysis as 3-O-[α-l-arabinopyranosyl-(1→2)-O-3-acetoxy-α-l-arabinopyranosyl]-6-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (55), 3-O-[α-l-rhamnopyranosyl-(1→2)-O-α-l-arabinopyranosyl-(1→2)-O-β-d-xylopyranosyl]-6-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (56), 3-O-[α-l-arabinopyranosyl-(1→2)-O-3,4-diacetoxy-α-l-arabinopyranosyl]-6-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (57), 3-O-[α-l-arabinopyranosyl-(1→2)-O-3-acetoxy-α-l-arabinopyranosyl]-6-O-β-d-glucopyranosyl-3β,6α,16β,25-tetrahydroxy-20(R),24(S)-epoxycycloartane (58), 3-O-[α-l-arabinopyranosyl-(1→2)-O-β-d-xylopyranosyl]-6-O-β-d-glucopyranosyl-3β,6α,16β,24α-tetrahydroxy-20(R),25-epoxycycloartane (59), and 3-O-[α-l-rhamnopyranosyl-(1→2)-O-α-l-arabinopyranosyl-(1→2)-O-β-d-xylopyranosyl]-6-O-β-d-glucopyranosyl-3β,6α,16β,24α-tetrahydroxy-20(R),25-epoxycycloartane (60). The authors stated that compounds 5960 were based on cyclocephalogenin as aglycone, more unusual in the plant kingdom, so far reported only from Astragalus spp. (Bedir et al. 1998a; Agzamova and Isaev 1999; Sukhina et al. 2007). In addition, two known cycloartane-type glycosides, oleifolioside B (Özipek et al. 2005) and astragaloside I (Kitagawa et al. 1983a); five known oleanane-type triterpene glycosides, azukisaponin V (Kitagawa et al. 1983e), azukisaponin V methyl ester (Mohamed et al. 1995), astragaloside VIII (Kitagawa et al. 1983c), astragaloside VIII methyl ester (Cui et al. 1992a), and 22-O-[β-d-glucopyranosyl-(1→2)-O-α-l-arabinopyranosyl]-3β,22β,24-trihydroxy-olean-12-ene (Yoshikawa et al. 1985); and the flavonol glycoside narcissin (Senatore et al. 2000) were characterized (Horo et al. 2010).

Compound 55; C48H80O19; [α]25D +28.4° (c 0.1, MeOH); νKBrmax cm−1: 3477 (>OH), 3041 (cyclopropane ring), 2940 (>CH), 1739 (C=O), 1264 and 1059 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 983.5198 (calcd. for C48H80O19Na, 983.5192). Compound 56; C52H88O22; [α]25D +37.2° (c 0.1, MeOH); νKBrmax cm−1: 3484 (>OH), 3037 (cyclopropane ring), 2949 (>CH), 1260 and 1064 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 1087.5669 (calcd. for C52H88O22Na, 1087.5665). Compound 57; C50H82O20; [α]25D +31.8° (c 0.1, MeOH); νKBrmax cm−1: 3471 (>OH), 3032 (cyclopropane ring), 2931 (>CH), 1741 (C=O), 1258-1050 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 1025.5294 (calcd. for C50H82O20Na, 1025.5297). Compound 58; C48H78O19; [α]25D +22.1° (c 0.1, MeOH); νKBrmax cm−1: 3488 (>OH), 3035 (cyclopropane ring), 2927 (>CH), 1732 (C=O), 1275 and 1030 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 981.5041 (calcd. for C48H78O19Na, 981.5035). Compound 59; C46H76O18; [α]25D +8.5° (c 0.1, MeOH); νKBrmax cm−1: 3481 (>OH), 3045 (cyclopropane ring), 2934 (>CH), 1280-1040 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 939.4932 (calcd. for C46H76O18Na, 939.4929). Compound 60; C52H86O22; [α]25D +11.7° (c 0.1, MeOH); νKBrmax cm−1: 3474 (>OH), 3049 (cyclopropane ring), 2937 (>CH), 1266-1052 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 1085.5511 (calcd. for C52H86O22Na, 1085.5508). The structures and 13C NMR data of the compounds (55–60) are presented below.

In 2011, from the roots of Astragalus ptilodes Boiss. var. cariensis Boiss. (Sect. Pterophorus), five known compounds, astragaloside VII [(3β,6α,16β,20R,24S)-20,24-epoxy-16-hydroxy-3-(β-d-xylopyranosyloxy)-9,19-cyclolanostane-6,25-diyl bis[β-d-glucopyranoside] (Bedir et al. 1999a), cyclosiversioside E (3β,6α,16β,20R,24S)-20,24-epoxy-16,25-dihydroxy-9,19-cyclolanostane-3,6-diyl bis[β-d-xylopyranoside]) (Svechnikova et al. 1982a), cyclosiversioside F (3β,6α,16β,20R,24S)-20,24-epoxy-16,25-dihydroxy-3-(β-d-xylopyranosyloxy)-9,19-cyclolanostan-6-yl β-d-glucopyranoside) (Svechnikova et al. 1982a), astragaloside I (3β,6α,16β,20R,24S)-3-[(2,3-di-O-acetyl-β-d-xylopyranosyl)oxy]-20,24-epoxy-16,25-dihydroxy-9,19-cyclolanostan-6-yl β-d-glucopyranoside) (Kitagawa et al. 1983a), and cyclosiversioside A (3β,6α,16β,20R,24R)-3-[(2,3-di-O-acetyl-β-d-xylopyranosyloxy]-20,24-epoxy-16,25-dihydroxy-9,19-cyclolanostan-6-yl β-d-xylopyranoside) (Svechnikova et al. 1982b), were isolated (Linnek et al. 2011).

In another study in 2011, eight new cycloartane-type triterpene glycosides, 3-O-[α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranosyl-(1→2)-β-d-xylopyranosyl]-6-O-β-d-xylopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (61), 3,6-di-O-β-d-xylopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (62), 3,6-di-O-β-d-xylopyranosyl-25-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (63), 3-O-β-d-xylopyranosyl-6,25-di-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (64), 6-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (65), 3-O-[α-l-arabinopyranosyl-(1→2)-β-d-xylopyranosyl]-3β,6α,16β,24α-tetrahydroxy-20(R),25-epoxycycloartane(66), 6-O-β-d-glucopyranosyl-3β,6α,16β,24α-tetrahydroxy-20(R),25-epoxycycloartane (67), and 6-O-β-d-xylopyranosyl-3β,6α,16β,24α-tetrahydroxy-20(R),25-epoxycycloartane (68), were isolated from Astragalus aureus Willd (Sect. Adiaspastus), along with ten known cycloartane-type glycosides, namely, 3-O-[α-l-rhamnopyranosyl-(1→2)-O-α-l-arabinopyranosyl-(1→2)-O-β-d-xylopyranosyl]-6-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (Horo et al. 2010), oleifolioside B (Özipek et al. 2005), cyclocanthoside G (Isaev et al. 1992), cyclocanthoside E (Isaev et al. 1992), 3-O-[α-l-rhamnopyranosyl-(1→2)-O-α-l-arabinopyranosyl-(1→2)-O-β-d-xylopyranosyl]-6-O-β-d-glucopyranosyl-3β,6α,16β,24α-tetrahydroxy-20(R),25-epoxycycloartane (Horo et al. 2010), 3-O-[α-l-arabinopyranosyl-(1→2)-O-β-d-xylopyranosyl]-6-O-β-d-glucopyranosyl-3β,6α,16β,24α-tetrahydroxy-20(R),25-epoxycycloartane (Horo et al. 2010), cyclocanthoside F (Agzamova and Isaev 1999), cyclocephaloside I (Bedir et al. 1998a), cyclotrisectoside (Sukhina et al. 2007), and macrophyllosaponin B (Çalış et al. 1996). The authors stated that aminoglycosides of cyclocanthogenin (65) and cyclocephalogenin (67, 68) were encountered for the first time. In this study, a number of cancer cell lines were used for measuring cytotoxic activities of all compounds, among which only compound 68 showed moderate cytotoxic activity against human breast cancer (MCF7) at 45 μM concentration (Gülcemal et al. 2011).

Compound 61; C51H86O21; [α]25D +37.2° (c 0.1, MeOH); νKBrmax cm−1: 3474 (>OH), 3035 (cyclopropane ring), 2953 (>CH), 1255 and 1068 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 1057.5563 (calcd. for C51H86O21Na, 1057.5559). Compound 62; C40H68O13; [α]25D +29.2° (c 0.1, MeOH); νKBrmax cm−1: 3487 (>OH), 3043 (cyclopropane ring), 2950 (>CH), 1269 and 1059 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 779.4561 (calcd. for C40H68O13Na, 779.4558). Compound 63; C46H78O18; [α]25D +35.6° (c 0.1, MeOH); νKBrmax cm−1: 3482 (>OH), 3040 (cyclopropane ring), 2945 (>CH), 1259 and 1051 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 941.5090 (calcd. for C46H78O18Na, 941.5086). Compound 64; C47H80O19; [α]25D +32.5° (c 0.1, MeOH); νKBrmax cm−1: 3477 (>OH), 3038 (cyclopropane ring), 2934 (>CH), 1263 and 1054 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 971.5197 (calcd. for C47H80O19Na, 971.5192). Compound 65; C36H62O10; [α]25D +27.8° (c 0.1, MeOH); νKBrmax cm−1: 3485 (>OH), 3047 (cyclopropane ring), 2930 (>CH), 1254 and 1061 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 677.4246 (calcd. for C36H62O10Na, 677.4241). Compound 66; C40H66O13; [α]25D +10.5° (c 0.1, MeOH); νKBrmax cm−1: 3488 (>OH), 3053 (cyclopropane ring), 2939 (>CH), 1274 and 1050 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 777.4405 (calcd. for C40H66O13Na, 777.4401). Compound 67; C36H60O10; [α]25D +15.2° (c 0.1, MeOH); νKBrmax cm−1: 3479 (>OH), 3048 (cyclopropane ring), 2947 (>CH), 1257 and 1065 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 675.4089 (calcd. for C36H60O10Na, 675.4084). Compound 68; C35H58O9; [α]25D +8.2° (c 0.1, MeOH); νKBrmax cm−1: 3471 (>OH), 3050 (cyclopropane ring), 2943 (>CH), 1268 and 1057 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 645.3983 (calcd. for C35H58O9Na, 645.3979). The structures and 13C NMR data of compounds 6168 are given below.

The study of the chemical constituents of Astragalus pycnocephalus var. pycnocephalus (Sect. Rhacophorus) has resulted in the isolation of four known cycloartane-type glycosides. Their structures were established as trojanoside H (Bedir et al. 1999b), astragaloside IV (Kitagawa et al. 1983a), astragaloside VIII (Kitagawa et al. 1983c), and astrasieversianin X (Gan et al. 1986) by the extensive use of 1D- and 2D-NMR experiments along with HRMS analyses and by comparison with literature values. In this report, the inhibitory activities of all compounds were tested against the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). All compounds showed strong inhibition against α-glucosidase, and they exhibited mild activity against β-glucosidase (Koz et al. 2011).

Studies on Astragalus stereocalyx Bornm (Sect. Stereocalyx) resulted the isolation of six new cycloartane-type triterpene glycosides. Structures of the newcompounds were determined as 3-O-[α-l-arabinopyranosyl-(1→2)-β-d-xylopyranosyl]-16-O-β-d-glucopyranosyl-3β,6α,16β,20(S),24(R), 25-hexahydroxycycloartane (69), 3-O-[α-l-arabinopyranosyl-(1→2)-β-d-xylopyranosyl]-3β,6α,16β,20(S),24(R),25-hexahydroxycycloartane (70), 3-O-[α-l-arabinopyranosyl-(1→2)-β-d-glucopyranosyl]-3β,6α,16β,20(S),24(R),25-hexahydroxycycloartane (71), 3-O-[α-l-arabinopyranosyl-(1→2)-β-d-glucopyranosyl]-24-O-β-d-glucopyranosyl-3β,6α,16β,24(R),25-pentahydroxycycloartane (72), 3-O-[α-l-arabinopyranosyl-(1→2)-β-d-glucopyranosyl]-16-O-β-d-glucopyranosyl-3β,6α,16β,24(R),25-pentahydroxycycloartane (73), and 3-O-{α-l-rhamnopyranosyl-(1→4)-[α-l-arabinopyranosyl-(1→2)]-β-d-glucopyranosyl}-3β,6α,16β,24(R),25-pentahydroxycycloartane (74). Additionally, six known cycloartane-type glycosides, askendoside C (Isaev et al. 1983b), askendoside F (Isaev 1995), askendoside G (Isaev 1996), 3-O-β-d-glucopyranosyl-16-O-β-d-glucopyranosyl-3β,6α,16β,24(R),25-pentahydroxycycloartane (Verotta et al. 2002), elongatoside (Çalış et al. 2008a), and trojanoside H (Bedir et al. 1999b), were isolated. The authors stressed that compounds 6971 were based on an aglycone possessing an unusual hydroxyl group at position 20. In this research, some cell lines including Hela (human cervical cancer), HT-29 (human colon cancer), U937 (human leukemia), and H446 (human lung cancer) were utilized for testing antiproliferative activity of the obtained compounds. A concentration range between 1 and 50 μM was chosen for testing, where only a few compounds showed weak activities. Hela was the only susceptible cell line to the compounds. While the compound 3-O-β-d-glucopyranosyl-16-O-β-d-glucopyranosyl-3β,6α,16β,24(R),25-pentahydroxycycloartane displayed an IC50 value of 10 μM against Hela cells, compounds 74, askendoside C, and askendoside G exhibited IC50 values of 29.9, 31.5, and 24.4 μM, respectively (Yalçın et al. 2012).

Compound 69; C46H78O19; [α]25D +27.2° (c 0.1, MeOH); νKBrmax cm−1: 3480 (>OH), 3039 (cyclopropane ring), 2961 (>CH), 1250 and 1072 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 957.5038 (calcd. for C46H78O19Na, 957.5035). Compound 70; C40H68O14; [α]25D +25.2° (c 0.1, MeOH); νKBrmax cm−1: 3475 (>OH), 3048 (cyclopropane ring), 2955 (>CH), 1260 and 1057 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 795.4509 (calcd. for C40H68O14Na, 795.4507). Compound 71; C41H70O15; [α]25D +28.6° (c 0.1, MeOH); νKBrmax cm−1: 3477 (>OH), 3036 (cyclopropane ring), 2948 (>CH), 1252 and 1067 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 825.4615 (calcd. for C41H70O15Na, 825.4612). Compound 72; C47H80O19; [α]25D +12.7° (c 0.1, MeOH); νKBrmax cm−1: 3482 (>OH), 3043 (cyclopropane ring), 2952 (>CH), 1263 and 1060 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 971.5196 (calcd. for C47H80O19Na, 971.5192). Compound 73; C47H80O19; [α]25D +10.8° (c 0.1, MeOH); νKBrmax cm−1: 3488 (>OH), 3045 (cyclopropane ring), 2940 (>CH), 1258 and 1064 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 971.5194 (calcd. for C47H80O19Na, 971.5192). Compound 74; C47H80O18; [α]25D +14.5° (c 0.1, MeOH); νKBrmax cm−1: 3470 (>OH), 3051 (cyclopropane ring), 2943 (>CH), 1268 and 1054 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 955.5246 (calcd. for C47H80O18Na, 955.5242). The structures and 13C NMR data of 69–74 are shown below.

In 2012, another phytochemical study was performed on Astragalus hareftae (Sect. Acanthophace), which was resulted in isolation of four new cycloartanes (hareftosides A–D) and a new oleanane-type triterpenoid (hareftoside E) along with 11 known compounds. Structures of the new compounds were established as 3,6-di-O-β-d-xylopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (75), 3,6,24-tri-O-β-d-xylopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (76), 3-O-β-d-xylopyranosyl-3β,6α,16β,25-tetra-hydroxy-20(R),25(S)-epoxycycloartane (77), 16-O-β-d-glucopyranosyl-3β,6α,16β,25-tetrahydroxy-20(R),24(S)-epoxycycloartane (78), and 3-O-[β-d-xylopyranosyl-(1→2)-O-β-d-glucopyranosyl-(1→2)-O-β-d-glucuronopyranosyl] soyasapogenol B (79) by the extensive use of 1D- and 2D-NMR experiments along with ESI-MS and HR-MS analyses. Known compounds were identified as cyclocanthoside E (Isaev et al. 1992), macrophyllosaponin B (Çalış et al. 1996), 3-O-β-d-xylopyranosyl-6,25-di-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (Gülcemal et al. 2011), oleifolioside B (Özipek et al. 2005), cyclocephaloside I (Bedir et al. 1998a), astrasieversianin X (Gan et al. 1986), trojanoside B (Bedir et al. 1999a), cycloastragenol (Kitagawa et al. 1983a), astragaloside IV (Kitagawa et al. 1983a), brachyoside B (Bedir et al. 1998b), and cyclodissectoside (Sukhina et al. 2007) and four known oleanane-type triterpene glycosides, azukisaponin V (Kitagawa et al. 1983e), dehydroazukisaponin V (Mohamed et al. 1995), wistariasaponin D (Konoshima et al. 1991), and astragaloside VIII (Kitagawa et al. 1983c), respectively (Horo et al. 2012).

Compound 75; C40H68O13; [α]25D +27.3° (c 0.1, MeOH); νKBrmax cm−1: 3460 (>OH), 3035 (cyclopropane ring), 2945 (>CH), 1260 and 1058 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 779.4564 (calcd. for C40H68O13Na, 779.4558). Compound 76; C45H76O17; [α]25D +24.3° (c 0.1, MeOH); νKBrmax cm−1: 3470 (>OH), 3030 (cyclopropane ring), 2950 (>CH), 1264 and 1060 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 911.4984 (calcd. for C45H76O17Na, 911.4980). Compound 77; C35H58O9; [α]25D +19.8° (c 0.1, MeOH); νKBrmax cm−1: 3480 (>OH), 3030 (cyclopropane ring), 2945 (>CH), 1260 and 1055 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 645.3982 (calcd. for C35H58O9Na, 645.3979). Compound 78; C36H60O10; [α]25D +20.8° (c 0.1, MeOH); νKBrmax cm−1: 3460 (>OH), 3040 (cyclopropane ring), 2935 (>CH), 1250 and 1050 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 675.4086 (calcd. for C36H60O10Na, 675.4084). Compound 79; C47H76O18; [α]25D +12.1° (c 0.1, MeOH); νKBrmax cm−1: 3448 (>OH), 2934 (>CH), 1658 (C=C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 951.4932 (calcd. for C47H76O18Na, 951.4929). The structures and 13C NMR data of compounds 75–79 are provided below.

Another study conducted in Karabey et al. (2012) reported on the isolation and structural elucidation of three new cycloartane-type triterpene glycosides from the roots of Astragalus schottianus Boiss. (Sect. Rhacophorus). By means of spectroscopic methods (IR, 1D- and 2D-NMR, HR-ESI-MS), their structures were established as 20(R),25-epoxy-3-O-β-d-xylopyranosyl-24-O-β-d-glucopyranosyl-3β,6α,16β,24α-tetrahydroxycycloartane (80), 20(R),25-epoxy-3-O-[β-d-glucopyranosyl(1→2)]-β-d-xylopyranosyl-24-O-β-d-glucopyranosyl-3β,6α,16β,24α-tetrahydroxycycloartane (81), and 3-O-β-d-xylopyranosyl-3β,6α,16β,20(S),24(S),25-hexahydroxycycloartane (82) (Karabey et al. 2012). According to the authors, compound 82 represents the second entry of the series of cycloartane-type compound possessing a 20-OH functional group in Astragalus genus. Moreover, in nature, only five compounds, obtained from Oxytropis bicolor and Astragalus stereocalyx , were reported to have such a substitution at C-20 and 3β,16β,20(S),24(S),25-pentahydroxycycloartane framework (Rong-Qi et al. 1991; Sun and Chen 1997; Yalçın et al. 2012).

Compound 80; C41H68O14; δC (C5D5N); HR-ESI-MS m/z [M + Na]+ 807.46042 (calcd. for C41H68O14Na, 807.45068). Compound 81; C47H78O20; δC (C5D5N); HR-ESI-MS m/z [M–Cl] 981.48275 (calcd. for C47H78O20Cl). Compound 82; C35H60O10; δC (C5D5N); HR-ESI-MS m/z [M–Cl] 675.38677 (calcd. for C35H60O10Cl, 675.38750). The structures and carbon chemical shifts of compounds 80, 81, and 82 are presented below.

Phytochemical investigation of Astragalus erinaceus (Sect. Rhacophorus) was resulted in isolation of a new cycloartane-type saponin, 3-O-[β-d-xylopyranosyl-(1→2)-β-d-xylopyranosyl]-6-O-β-d-glucuronopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (83). Additionally, five known saponins, cyclodissectoside (Sukhina et al. 2007), cycloastragenol (Kitagawa et al. 1983a), 6-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (Gülcemal et al. 2011), oleifolioside B (Özipek et al. 2005), and 3,6-di-O-β-d-xylopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (Gülcemal et al. 2011), were also identified. The authors stated that the glucuronic acid moiety was an unusual finding, and compound 83 was representing second example of such framework in cycloartane chemistry (Savran et al. 2012).

Compound 83; C46H77O19; [α]25D +30.8° (c 0.1, MeOH); δC (CD3OD); HR-ESI-MS m/z [M + Na]+ 955.4882 (calcd. for C46H77O19Na, 955.4879). The structure and 13C chemical shifts are provided below for 83.

Another phytochemical study was performed on Astragalus angustifolius (Sect. Melanocercis) which was resulted in isolation of six cycloartane- (8489) and four oleanane-type triterpenoids (9093) together with five known triterpene glycosides. Structures of the compounds were established as 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-glucopyranosyl]-16-O-hydroxyacetoxy-3β,6α,16β,25 tetrahydroxy-20(R),24(S)-epoxycycloartane (84), 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-glucopyranosyl]-16-O-hydroxyacetoxy-3β,6α,16β,23α,25-pentahydroxy-20(R),24(S)-epoxycycloartane (85), 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-glucopyranosyl]-3β,6α,25-trihydroxy-20(R),24(S)-epoxycycloartane-16-one (86), 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-glucopyranosyl]-3β,6α,16β,25-tetrahydroxy-20(R),24(R)-epoxycycloartane (87), 3-O-β-d-xylopyranosyl-6-O-α-l-rhamnopyranosyl-3β,6α,16β,25-tetrahydroxy-20(R),24(R)-epoxycycloartane (88), 6-O-α-l-rhamnopyranosyl-3β,6α,16β,25-tetrahydroxy-20(R),24(R)-epoxycycloartane (89), 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranosyl-(1→2)-β-d-glucuronopyranosyl]-3β,21β,22α,24,29-pentahydroxyolean-12-ene (90), 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranosyl-(1→2)-β-d-glucuronopyranosyl]-3β,22β,24-trihydroxyolean-12-en-29-oic acid (91), 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranosyl-(1→2)-β-d-glucuronopyranosyl]-22-O-α-l-arabinopyranosyl-3β,22β,24-trihydroxyolean-12-ene (92), and 29-O-β-d-glucopyranosyl-3β,22β,24,29-tetrahydroxyolean-12-ene (93) by the extensive use of 1D- and 2D-NMR experiments along with ESIMS and HRMS analysis. Known compounds were identified as 25-O-glucopyranosylcycloastragenol (Bedir et al. 1999a), cycloaraloside D (Isaev 1991), 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-glucopyranosyl]-25-O-β-d-glucopyranosyl-20(R),24(S)-epoxy-3β,6α,16β,25-tetrahydroxycycloartane (Polat et al. 2010), astrojanoside A (Bedir et al. 1999a), and astragaloside VIII (Kitagawa et al. 1983c). The authors reported that compounds 8486 were glycosides of cycloastragenol, while compounds 8789 had the C-24 epimer of cycloastragenol as aglycone, reported for the first time in nature. In this study, antiproliferative activity in Hela, H-446, HT-29, and U937 cell lines was tested for all compounds. Compound 91 was the only compound that displayed a weak activity against both Hela and HT-29 cell lines with IC50 values of 36 and 50 μM, respectively (Gülcemal et al. 2012).

Compound 84; C44H72O16; [α]25D +19.01° (c 0.1, MeOH); νKBrmax cm−1: 3470, 3040, 2950, 1260 and 1058; δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 879.4722 (calcd. for C44H72O16Na, 879.4718). Compound 85; C44H72O17; [α]25D +41.4° (c 0.1, MeOH); νKBrmax cm−1: 3480, 3035, 2945, 1260 and 1055; δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 895.4669 (calcd. for C44H72O17Na, 895.4667). Compound 86; C42H68O14; [α]25D −23.1° (c 0.1, MeOH); νKBrmax cm−1: 3475, 3030, 2948, 1740, 1258 and 1050; δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 819.4512 (calcd. for C42H68O14Na, 819.4507). Compound 87; C42H70O14; [α]25D −5.21° (c 0.1, MeOH); νKBrmax cm−1: 3460, 3038, 2935, 1250 and 1050; δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 821.4666 (calcd. for C42H70O14Na, 821.4663). Compound 88; C41H68O13; [α]25D +15.1° (c 0.1, MeOH); νKBrmax cm−1: 3460, 3035, 2940, 1240 and 1050; δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 791.4561 (calcd. for C41H68O13Na, 791.4558). Compound 89; C36H60O9; [α]25D −8.09° (c 0.1, MeOH); νKBrmax cm−1: 3450, 3042, 2938, 1250 and 1052; δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 659.4139 (calcd. for C36H60O9Na, 659.4135). Compound 90; C47H76O19; [α]25D −10.9° (c 0.1, MeOH); νKBrmax cm−1: 3455, 2945, 1666, 1252 and 1052; δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 967.4881 (calcd. for C47H76O19Na, 967.4879). Compound 91; C47H74O19; [α]25D +7.12° (c 0.1, MeOH); νKBrmax cm−1: 3451, 2937, 1735, 1658, 1248 and 1048; δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 965.4726 (calcd. for C47H74O19Na, 965.4722). Compound 92; C52H84O21; [α]25D −8.54° (c 0.1, MeOH); νKBrmax cm−1: 3446, 2930, 1730, 1648, 1245 and 1052; δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 1067.5406 (calcd. for C52H84O21Na, 1067.5403). Compound 93; C36H60O9; [α]25D +27.7° (c 0.1, MeOH); νKBrmax cm−1: 3440, 2933, 1645, 1240 and 1044; δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 659.4139 (calcd. for C36H60O9Na, 659.4135). The structures and carbon chemical shifts of compounds 8493 are shown below.

Another phytochemical investigation was published in 2013, and a new cycloartane-type glycoside, (20R,24S)-3-O-[α-l-arabinopyranosyl-(1→2)-β-d-xylopyranosyl]-20,24-epoxy-16-O-β-d-glucopyranosyl-3β,6α,16β,25-tetrahydroxycycloartane (94), and a new glycoside, 3-O-[β-d-apiofuranosyl-(1→2)-β-d-glucopyranosyl]maltol (95), were isolated from Astragalus halicacabus (Sect. Halicacabus) together with seven known cycloartane-type glycosides, i.e., cyclocanthoside D (Isaev et al. 1992); askendosides D (Isaev et al. 1983a), F (Isaev 1995), and G (Isaev 1996); cyclosieversioside G (Svechnikova et al. 1983); cyclostipuloside A (Karimov et al. 1998); and elongatoside (Çalış et al. 2008a), and a known maltol glucoside, 3-O-β-d-glucopyranosylmaltol (Sala et al. 2001). The authors commented that maltol glycoside was reported for the first time in the Astragalus genus and even in the Fabaceae family (Djimtombaye et al. 2013).

Compound 94; C46H76O18; [α]25D +41.4° (c 0.1, MeOH); νKBrmax cm−1: 3480 (>OH), 3035 (cyclopropane ring), 2945 (>CH), 1260 and 1055 (C–O–C); δC (CD3OD); HR-ESI-MS m/z [M + Na]+ 939.4991 (calcd. for C46H76O18Na, 939.4990). Compound 95; C17H24O12; [α]25D −78.9° (c 0.1, MeOH); νKBrmax cm−1: 3376, 1650; δC (CD3OD); HR-ESI-MS m/z [M + Na]+ 443.1199 (calcd. for C17H24O12Na, 443.1182). The structures and 13C chemical shifts are given below for 94 and 95.

From Astragalus tauricolus (Sect. Malacothrix), on the basis of the results of the online screening by HPLC–ESIMSn, ten new oleanane-type triterpene glycosides were isolated and established by spectral methods, 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranosyl-(1→2)-β-d-glucuronopyranosyl]-29-O-β-d-glucopyranosyl-3β,22β,24-trihydroxyolean-12-en-29-oic acid (96), 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-glucopyranosyl-(1→2)-β-d-glucuronopyranosyl]-29-O-β-d-glucopyranosyl-3β,22β,24,29-tetrahydroxyolean-12-ene (97), 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranosyl-(1→2)-β-d-glucuronopyranosyl]-21-O-α-l-rhamnopyranosyl-3β,21β,22α,24-tetrahydroxyolean-12-ene (98), 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-glucopyranosyl-(1→2)-β-d-glucuronopyranosyl]-21-O-α-l-rhamnopyranosyl-3β,21β,22α,24-tetrahydroxyolean-12-ene (99), 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-glucopyranosyl-(1→2)-β-d-glucuronopyranosyl]-29-O-β-d-glucopyranosyl-3β,22β,24,-trihydroxyolean-12-en-29-oic acid (100), 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranosyl-(1→2)-β-d-glucuronopyranosyl]-22-O-α-l-rhamnopyranosyl-3β,22β,24-trihydroxyolean-12-ene (101), 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-glucopyranosyl-(1→2)-β-d-glucuronopyranosyl]-3β,24-dihydroxyolean-12-ene-22-oxo-29-oic acid (102), 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-glucopyranosyl-(1→2)-β-d-glucuronopyranosyl]-3β,21β,22α,24,29-pentahydroxyolean-12-ene (103), 3-O-[β-d-glucopyranosyl-(1→2)-β-d-glucuronopyranosyl]-29-O-β-d-glucopyranosyl-3β,22β,24,-trihydroxyolean-12-en-29-oic acid (104), and 3-O-[β-d-xylopyranosyl-(1→2)-β-d-glucuronopyranosyl]-29-O-β-d-glucopyranosyl-3β,22β,24,-trihydroxyolean-12-en-29-oic acid (105), along with 12 known oleanane-type glycosides, namely, astrojanoside A (Bedir et al. 1999a), melilotus-saponin O2 (Hirakawa et al. 2000), 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranosyl-(1→2)-β-d-glucuronopyranosyl]-3β,21β,22α,24,29-pentahydroxyolean-12-ene (Gülcemal et al. 2012), azukisaponin V (Kitagawa et al. 1983e), wistariasaponin B2 (Konoshima et al. 1989), astragaloside VIII (Kitagawa et al. 1983c), wistariasaponin B1 (Konoshima et al. 1989), cloversaponin IV (Sakamato et al. 1992), azukisaponin II (Kitagawa et al. 1983f), wistariasaponin D (Konoshima et al. 1991), dehydroazukisaponin V (Mohamed et al. 1995), and 3-O-β-d-glucuronopyranosyl-soyasapogenin B (Udayama et al. 1998). The authors commented that the phytochemical investigation of A. tauricolus showed only oleanane-type triterpene glycosides and no cycloartane-type glycosides, the main constituents of most Astragalus spp., sharing this peculiar feature with a limited group of Astragalus spp. [A. hamosus (Ionkova 1991), A. complanatus (Cui et al. 1992a), A. sinicus (Cui et al. 1992b), and A. corniculatus (Krasteva et al. 2006, 2007)]. Moreover, an HPLC–ESIMSn approach was used to characterize astragalosides in Radix Astragali [Xu et al. 2007; Zu et al. 2009; Chu et al. 2010), but no HPLC–ESIMSn study was addressed to oleanane-type triterpene saponins in Astragalus spp. In this study, antiproliferative activity of the compounds was also investigated against some cell lines including human breast cancer (MCF-7), human lung adenocarcinoma (A549), human prostate cancer (PC-3), and human leukemia (U937) cell lines. Compound 103 was the only compound exhibiting moderate activity with an IC50 of 22 μM against human leukemia cell line (U937) (Gülcemal et al. 2013).

Compound 96; C53H84O24; [α]25D +13.1° (c 0.1, MeOH); νKBrmax cm−1: 3428 (>OH), 2934 (>CH), 1680 (C=O), 1658 (C=C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 1127.5262 (calcd. for C53H84O24Na, 1127.5250). Compound 97; C54H88O24; [α]25D +9.3° (c 0.1, MeOH); νKBrmax cm−1: 3442 (>OH), 2930 (>CH), 1670 (C=O), 1655 (C=C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 1143.5573 (calcd. for C54H88O24Na, 1143.5563). Compound 98; C53H86O22; [α]25D +22.4° (c 0.1, MeOH); νKBrmax cm−1: 3450 (>OH), 2938 (>CH), 1680 (C=O), 1660 (C=C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 1097.5515 (calcd. for C53H86O22Na, 1097.5508). Compound 99; C54H88O23; [α]25D +21.1° (c 0.1, MeOH); νKBrmax cm−1: 3430 (>OH), 2948 (>CH), 1670 (C=O), 1656 (C=C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 1127.5625 (calcd. for C54H88O23Na, 1127.5614). Compound 100; C54H86O25; [α]25D +15.6° (c 0.1, MeOH); νKBrmax cm−1: 3435 (>OH), 2925 (>CH), 1660 (C=C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 1157.5363 (calcd. for C54H86O25Na, 1157.5356). Compound 101; C53H86O21; [α]25D +19.6° (c 0.1, MeOH); νKBrmax cm−1: 3443 (>OH), 2935 (>CH), 1668 (C=C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 1081.5567 (calcd. for C53H86O21Na, 1081.5559). Compound 102; C48H74O20; [α]25D +9.8° (c 0.1, MeOH); νKBrmax cm−1: 3430 (>OH), 2938 (>CH), 1650 (C=C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 993.4682 (calcd. for C48H74O20Na, 993.4671). Compound 103; C48H78O20; [α]25D +16.8° (c 0.1, MeOH); νKBrmax cm−1: 3438 (>OH), 2930 (>CH), 1655 (C=C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 997.4989 (calcd. for C48H78O20Na, 997.4982). Compound 104; C48H76O21; [α]25D +16.8° (c 0.1, MeOH); νKBrmax cm−1: 3445 (>OH), 2928 (>CH), 1655 (C=C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 1011.4785 (calcd. for C48H76O21Na, 1011.4777). Compound 105; C47H74O20; [α]25D +11.5° (c 0.1, MeOH); νKBrmax cm−1: 3440 (>OH), 2934 (>CH), 1650 (C=C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 981.4683 (calcd. for C47H74O20Na, 981.4671). The structures and 13C data of the compounds (96–105) are presented below.

In 2014, a new cycloartane-type triterpene glycoside, 3-O-[α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranosyl-(1→2)-β-d-glucopyranosyl]-25-O-β-d-xylopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (krugianoside A, 106), was isolated from the roots of Astragalus plumosus var. krugianus Chamb.&Matthews (Sect. Rhacophorus), together with 15 known triterpene glycosides, namely, 6-O-β-d-glucopyranosyl-3β,6α,16β,24α-tetrahydroxy-20(R),25-epoxycycloartane (Gülcemal et al. 2011), cyclocephaloside I (Bedir et al. 1998a), 3-O-[α-l-arabinopyranosyl-(1→2)-O-β-d-xylopyranosyl]-6-O-β-d-glucopyranosyl-3β,6α,16β,24α-tetrahydroxy-20(R),25-epoxycycloartane (Horo et al. 2010), 6-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (Gülcemal et al. 2011), 3-O-[α-l-arabinopyranosyl-(1→2)-O-β-d-xylopyranosyl]-3β,6α,16β,24α-tetrahydroxy-20(R),25-epoxycycloartane (Gülcemal et al. 2011), cyclocanthoside E (Isaev et al. 1992), oleifoliosides B (Özipek et al. 2005), 3-O-[α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranosyl-(1→2)-O-β-d-xylopyranosyl]-6-O-β-d-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane (Horo et al. 2010), cycloastragenol (Kitagawa et al. 1983a), brachyoside B (Bedir et al. 1998b), cycloaraloside A (Isaev et al. 1989), cyclogaleginoside B (Alaniya et al. 1984), cycloaraloside D (Isaev 1991), elongatoside (Çalış et al. 2008a), and astragaloside IV (Kitagawa et al. 1983a). In this report, cytotoxic activity of all compounds was evaluated in human skin fibroblast WS1 cells, which revealed no cytotoxicity. The antioxidant potential was also examined for the compounds. Compounds 106 and oleifoliosides B prevented elevation of ROS induced by t-BOOH, emphasizing the potential activity of these compounds to protect fibroblasts from oxidative stress (Denizli et al. 2014).

Compound 106; C52H88O22; [α]25D +25.6° (c 0.1, MeOH); νKBrmax cm−1: 3470 (>OH), 3055 (cyclopropane ring), 2940 (>CH), 1265 and 1055 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 1087.5669 (calcd. for C52H88O22Na, 1087.5665). The structure and 13C chemical shifts are given below for compound 106.

Another phytochemical study was performed on Astragalus pennatulus (Sect. Rhacophorus), which resulted in isolation of four new cycloartane- and a new oleanane-type triterpenoids together with five known cycloartane-type glycosides. Structures of the compounds were established as 3-O-β-d-xylopyranosyl-6-O-β-d-glucopyranosyl-3β,6α,16β-trihydroxy-24-oxo-20(R),25-epoxycycloartane (107), 3-O-[β-d-glucuronopyranosyl-(1→2)-β-d-xylopyranosyl]-3β,16β,24α-trihydroxy-20(R),25-epoxycycloartane (108), 3-O-[β-d-glucuronopyranosyl-(1→2)-β-d-xylopyranosyl]-3β,16β,25-trihydroxy-20(R),24(S)-epoxycycloartane (109), 3,25-di-O-β-d-glucopyranosyl-6-O-β-d-xylopyranosyl-3β,6α,16β,25-tetrahydrox-20(R),24(S)-epoxycycloartane (110), and 29-O-α-l-rhamnopyranosyl-abrisapogenol B (111) by the extensive use of 1D- and 2D-NMR experiments along with ESIMS and HRMS analysis. Known compounds were identified as cyclodissectoside (Sukhina et al. 2007), hareftoside C (Horo et al. 2012), 6-O-β-d-glucopyranosyl-3β,6α,16β,24α-tetrahydroxy-20(R),25-epoxycycloartane (Gülcemal et al. 2011), cyclocephaloside I (Bedir et al. 1998a), and astragaloside IV (Kitagawa et al. 1983a). The authors stated that the aglycone of compound 107, 3β,6α,16β-trihydroxy-24-oxo-20(R),25-epoxycycloartane, was reported for the first time. In this report, three cancer cell lines including A549 (human lung adenocarcinoma), A375 (human melanoma), and DeFew (human B lymphoma) cells were used for testing cytotoxicity of the isolated compounds. There was no significant cytotoxicity in any of the tested compounds (Un et al. 2016).

Compound 107; C41H66O14; [α]25D −60.4° (c 0.03, MeOH); νKBrmax cm−1: 3455 (>OH), 3030 (cyclopropane ring), 2940 (>CH), 1260 and 1055 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 805.4354 (calcd. for C41H66O14Na, 805.4350). Compound 108; C41H66O14; [α]25D −50.7° (c 0.06, MeOH); νKBrmax cm−1: 3460 (>OH), 3030 (cyclopropane ring), 2950 (>CH), 1264 and 1055 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 805.4353 (calcd. for C41H66O14Na, 805.4350). Compound 109; C41H66O14; [α]25D −12.7° (c 0.07, MeOH); νKBrmax cm−1: 3465 (>OH), 3030 (cyclopropane ring), 2955 (>CH), 1260 and 1060 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 805.4355 (calcd. for C41H66O14Na, 805.4350). Compound 110; C47H78O19; [α]25D −117.3° (c 0.04, MeOH); νKBrmax cm−1: 3455 (>OH), 3035 (cyclopropane ring), 2935 (>CH), 1250 and 1050 (C–O–C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 969.5037 (calcd. for C47H78O19Na, 969.5035). Compound 111; C36H60O8; [α]25D −93.2° (c 0.04, MeOH); νKBrmax cm−1: 3460 (>OH), 2934 (>CH), 1658 (C=C); δC (CD3OD); HR-MALDITOF-MS m/z [M + Na]+ 643.4190 (calcd. for C36H60O8Na, 643.4186). The structures and 13C chemical shifts are provided below for compounds 107111.

In 2016, a study was performed on another Turkish species; Astragalus tmoleus Boiss. var. tmoleus (Sect. Pterophorus) and known cycloartane-type saponins, astrasieversianins I (Gan et al. 1986) and II (Gan et al. 1986), astragaloside IV (Kitagawa et al. 1983a), cyclocephaloside II (Bedir et al. 1998b), and acetylastragaloside I (Kitagawa et al. 1983a), were isolated (Avunduk et al. 2016).

Phytochemical investigation of Astragalus lycius Boiss (Sect. Onobrychium) was resulted in isolation of eight known secondary metabolites. Their structures were established as 5,5′-dihydroxy-3′-methoxy-isoflavone-7-O-β-d-glucoside (Vitor et al. 2004), genistin (Vitor et al. 2004), sissotrin (Vitor et al. 2004), 5,4′-dimethoxy-isoflavone-7-O-β-d-glucopyranoside (Vitor et al. 2004), (7S,8R)-5-methoxydehydrodiconiferyl alcohol-4-O-β-d-glucopyranoside (Machida and Sakamoto 2009), 4-O-lariciresinol-glucoside (Kurkin et al. 1991), 2-phenylethyl-β-d-glucopyranoside (Wu et al. 2011), and β-sitosterol-3-O-β-d-glucopyranoside (Nyongha et al. 2010) by the extensive use of 1D- and 2D-NMR experiments along with HRMS analyses and by comparison with literature values. The authors reported that the first seven compounds were reported for the first time from Astragalus genus. Interestingly, no cycloartane- or oleanane-type triterpene glycoside, the main constituents of Astragalus spp., was isolated. This peculiar feature characterizes a very limited group of Astragalus spp. such as Sect. Hymenostegis [A. lagurus (Guzhva et al. 1984)] and Sect. Vulneraria [A. vulneraria (Bedir et al. 2000b), A. onobrychis Guzhva et al. 1992)]. In this study, all the isolated compounds were investigated for their cytotoxic activities against a number of cancer cell lines [PC3 (human prostate carcinoma), HT-29 (human colon carcinoma), MDA-MB-231 (human breast carcinoma)] and a transformed cell line [HEK 293 (human embryonic kidney 293)], in which only 4-O-lariciresinol-glucoside represented a strong and selective activity against human colon carcinoma (HT-29) at 2.69 μM concentration (Horo et al. 2016).

The immunostimulatory effect of 19 cycloartane-type triterpene glycosides was examined (Bedir et al.); furthermore the bioactivity of macrophyllosaponins B–D; cyclocanthoside D and E; astrasieversianin II and X; trojanoside A and H; cyclocephaloside I; astragaloside I, II, IV, VI, and VII; brachyoside B; askendoside G; and cephalatoside A; cycloastragenol which previously isolated from A. oleifolius, A. prusianus, A. microcephalus, A. trojanus, A. cephalotes, and A. melanophrurius was tested using a transcription-based bioassay for nuclear factor-kappa B (NF-kappa B) activation in a human macrophage/monocyte cell line, THP-1. All compounds were inactive at 100 μg/mL except astragaloside I, which increased NF-kappa B directed luciferase expression up to 65% compared with maximal stimulation by E. coli lipopolysaccharide (LPS) at 10 μg/mL. With addition of 50 ng/mL LPS to the compounds, none of them were active at low dosage levels (0.1 μg/mL). On the other hand, astragaloside I increased mRNA expression of the inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α), which was measured using reverse transcriptase-polymerase chain reaction (RT)-PCR (Bedir et al. 2000a).

In the year of 2005, the gastroprotective effect of astragaloside IV, a cycloartane-type triterpene glycoside isolated from Astragalus zahlbruckneri, was measured. In addition to this, rolls of prostaglandins, sulfhydryls, and nitric oxide were also investigated. For this, astragaloside IV (3–30 mg kg−1) which was given orally to the tested mice depending on dose reduced the ethanol-induced gastric hemorrhagic lesions. The results suggested that the combination of NG-nitro-largininemethyl ester (70 mg kg−1, ip), a nitric oxide (NO)-synthase inhibitor, with astragaloside IV suspended in Tween 80 at 3, 10, and 30 mg kg−1 showed 15, 37, and 52% gastroprotection, respectively. Dose-dependent treatment confirmed that astragaloside IV with 30 mg kg−1 had the highest ulcer inhibition.

On the other hand, it was reported that the effect of astragaloside IV was not limited by inhibition of prostaglandin synthesis with indomethacin (10 mg kg−1, s.c.) and the block of endogenous sulfhydryls with N-ethylmaleimide (NEM , 10 mg kg−1, s.c.) (Navarrete et al. 2005).

In the year of 2005, another study was performed for the investigation of immunostimulating effect of 13 cycloartane- and 1 oleanane-type triterpene saponins isolated from Turkish species (Astragalus brachypterus, A. cephalotes, A. microcephalus, and A. trojanus), as well as methanol extracts from the roots of three Astragalus species (A. cephalotes, A. oleifolius, and A. trojanus). Cytokine concentrations of interleukins IL-1 (interleukin-1) and IL-8 (interleukin-8) and TNF-α after bacterial lipopolysaccharide (LPS) stimulation and IL-2 (interleukin-2) and IL-4 (interleukin-4) and INF-ɣ (interferon gamma) after phorbolacetate (PHA) stimulation were determined utilizing commercial enzyme-linked immunosorbent assay (ELISA) kits. All triterpene saponins, which were tested in the mentioned study (brachyoside A, brachyoside C, cycloastragenol, astragaloside I, brachyoside B, cyclocephaloside II, astragaloside II, astragaloside VII, trojanoside A, cyclocanthoside E, trojanoside H, cyclocephaloside I, astragaloside I, astrojanoside A: 3-O-(α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranosyl-(1→2)-β-d-glucuronopyranosyl)-29-O-β-d-glucopyranosyl-3β,22β,24,29-tetrahydroxyolean-12-en), presented a substantial IL-2-inducing activity between 35.9% and 139.6%. IL-2 is a cytokine produced by activated T cells with powerful immunostimulatory and antineoplastic properties. Among the extracts, the highest activity was obtained from A. oleifolius (141.2%). Glycosides of 20,24-epoxy and 20,25-epoxy cycloartanes showed higher IL-2-inducing activity than those of acyclic-cycloartane derivatives; in addition to this, in aglycone of 20,24-epoxy, cycloartanes in cycloastragenol also showed higher IL-2-inducing activity. Especially the activity of astragaloside VII, a tridesmosidic glycoside of cycloastragenol, was the most remarkable. Additionally, the oleanane-type triterpene saponins represented a prominent IL-2-inducing activity (Yeşilada et al. 2005).

In the year of 2011, another study was carried out for determination of in vitro growth stimulatory and in vivo wound healing properties of four cycloartane-type saponins that are present in Turkish Astragalus species as major chemical entities (astragaloside IV, cycloastragenol, cyclocephaloside I, and cyclocanthoside E). The obtained results indicated that cycloartane-type saponins of Astragalus genus are able to promote wound healing based on proliferation and migration in scratch assay, proliferation in MTT assay, and in vivo wound model study. Although all the obtained compounds could increase both migration and fibroblast proliferation, the most prominent were for cycloastragenol (CA), astragaloside IV (AG), and cyclocanthoside E (CCE). CA at 1 ng/mL showed a remarkable effect upon migration, whereas AG and CCE had their highest activities at 10 ng/mL. Simultaneously, AG and CCE at 10 ng/mL and CA at 1 ng/mL showed the highest proliferation rates in MTT assay. The results also showed that the topical treatments of Astragalus cycloartanes improve healing of subsequently induced abrasion skin wounds in rats compared to the control. At the end of 14-day treatment period, it was reported that 5% CA preparation was found to be the most remarkable in the treated skin. Histological researches also confirmed that the group treated by CA had a greater cell density, more newly formed blood vessels and more regularly organized dermis (linear alignment) compared to the other groups (Sevimli-Gür et al. 2011).

The evaluation of hemolytic activities referring to two immunomodulator Astragalus saponins macrophyllosaponin B (Mac B) from Astragalus oleifolius DC and astragaloside VII (Ast VII) from Astragalus trojanus Stev. and their adjuvant potentials on the cellular and humoral immune responses of Swiss albino mice against BSA (bovine serum albumin) were studied. The hemolytic activity of Mac B and Ast VII was measured using 0.5% rabbit red blood cell. According to the final results, no hemolytic activity was observed at concentrations of 2.5–500 μg/mL. Results referring to the effect of Ast VII and Mac B on mitogen- and BSA-stimulated splenocyte proliferation in BSA-immunized mice represented that LPS-stimulated splenocyte proliferation in the mice immunized with BSA/Ast VII and BSA/Mac B was significantly higher than that in the BSA control group. It was reported that the effect was dose dependent since BSA-induced splenocyte proliferation in the BSA-immunized mice was enhanced by Ast VII as well as Mac B in different doses. Mac B and Ast VII showed a slight hemolytic effect, with 0.42 and 0.54% values, respectively, while the results for the effects of Ast VII and Mac B on the BSA-specific serum antibody response represented that the serum IgG (immunoglobulin G), IgG1 (immunoglobulin G1), and IgG2b (immunoglobulin G2b), antibody levels immunized with BSA, were remarkably increased by Ast VII (120 μg), Mac B (90 μg), and Freund’s comparing to the control group. For adjuvant activity, on days 1 and 15, Swiss albino mice were immunized with only BSA 100 μg or with BSA 100 μg dissolved in saline containing Ast VII (30, 60, 120, and 240 μg), Mac B (30, 60, 90, and 120 μg), or Freund’s adjuvant; 2 weeks after the last immunization for concanavalin A (Con A)-, lipopolysaccharide (LPS)-, and BSA-stimulated splenocyte proliferation assay, sera and splenocytes were collected, and BSA-specific antibodies in serum were measured. Moreover, 2 weeks after the last immunization, the IFN-γ and IL-4 levels in the sera were detected using ELISA. Ast VII (120 μg) and Mac B (90 μg) were found to stimulate IFN-γ production such as Freund’s 2 weeks after the last immunization as compared to the control. Results showed that Ast VII and Mac B generate essential specific antibody and cellular response against BSA in mice; it can be confirmed that the tested molecules have potentials as a new class saponin adjuvant (Nalbantsoy et al. 2011).

In the year of 2012, immunomodulatory properties and in vitro anti-inflammatory activities of cycloartane-type saponins from Astragalus species were studied in mice. For this, the ability of LPS + Ast VII and LPS + Mac B to induce IL-1β, TGF-1β, TNF-α, IL-2, IL-4, and IFN-γ production was tested. Groups of five male Swiss albino mice were immunized ip with LPS (12.5 μg)/AST VII (60 μg) and LPS (12.5 μg)/Mac B (60 μg) on day 1 and AST VII (60 μg) and Mac B (60 μg) alone on day 2. The cytokine levels in the sera were detected 4 h after the last immunization using ELISA; the results suggested that AST VII and Mac B increased the concentration of Th1 (T helper 1) cytokine release (IL-2 and IFN-γ) and suppressed the concentration of Th2 (T helper 2) cytokine production (IL-4) remarkably. The results referring to the immunohistochemical studies exhibited that both IL-Rα (CD25) and CD69 surface receptors justifying the Th1 cytokine release were induced. According to the final results, compounds did not affect either NF-κB or NAG-1 (nonsteroidal anti-inflammatory drug-activated gene) activity; on the other hand inhibition of inducible nitric oxide synthase (iNOS) activity was inhibited by Mac B with half maximal inhibitory concentration (IC50) of 156 μg/mL. Although Ast VII and Mac B had no significant effect on the inflammatory cellular targets in vitro, they resulted in strong immunoregulatory effects without the stimulation of inflammatory cytokines in mice (Nalbantsoy et al. 2012).

Chemotaxonomy

Until now, as mentioned before , 31 out of 447 Turkish Astragalus species, which were chosen from 14 different sections, have been investigated for their secondary metabolite contents. Most of the studied sections, namely, Sect. Adiaspastus [A. aureus (Gülcemal et al. 2011)], Sect. Christiana [A. gilvus Boiss (Tabanca et al. 2005), A. melanophrurius (Çalış et al. 1997)], Sect. Halicacabus [A. halicacabus (Djimtombaye et al. 2013)], Sect. Macrophyllium [A. oleifolius (Çalış et al. 1996; Bedir et al. 2000c; Özipek et al. 2005)], Sect. Proselius [A. campylosema Boiss. ssp. campylosema (Çalış et al. 2008b), A. elongatus (Çalış et al. 2008a)], Sect. Pterophorus [A. brachypterus (Bedir et al. 1998b), A. baibutensis (Çalış et al. 2006), A. ptilodes Boiss. var. cariensis Boiss (Linnek et al. 2011), A. tmoleus var. tmoleus (Avunduk et al. 2016)], Sect. Rhacophorus [A. amblolepis (Polat et al. 2009), A. cephalotes var. brevicalyx (Çalış et al. 1999), A. erinaceus (Savran et al. 2012), A. microcephalus (Bedir et al. 1998a, b), A. plumosus var. krugianus (Denizli et al. 2014), A. prusianus (Bedir et al. 2001b), A. schottianus (Karabey et al. 2012), A. zahlbruckneri (Çalış et al. 2001)], and Sect. Stereocalyx [A. stereocalyx Bornm. (Yalçın et al. 2012)], provided cycloartane glycosides ; however, cycloartane- and oleanane-type saponins were encountered together in a few sections: Sect. Acanthophace [A. hareftae (Horo et al. 2012), A. icmadophilus (Horo et al. 2010)], Sect. Eustales [A. flavescens (Konoshima et al. 1989)], Sect. Melanocercis [A. angustifolius (Gülcemal et al. 2012)], Sect. Pterophorus [A. wiedemannianus Fischer (Polat et al. 2010), A. trojanus (Bedir et al. 1999a, b, 2001a)], and Sect. Rhacophorus [A. pennatulus (Un et al. 2016), Astragalus pycnocephalus var. pycnocephalus (Koz et al. 2011)]. The Sect. Malacothrix [A. tauricolus (Gülcemal et al. 2013)] provided oleanane-type saponins exclusively and no cycloartane-type glycosides, the main components of Astragalus spp., sharing this uncharacteristic feature with a limited group of Astragalus spp. [A. hamosus (Ionkova 1991), A. complanatus (Cui et al. 1992a), A. sinicus (Cui et al. 1992b), and A. corniculatus (Krasteva et al. 2006, 2007)]. A. lycius (Horo et al. 2016), belonging to Section Onobrychium , comprises only phenolic- and flavonoid-type glycosides. Moreover, A. vulneraria (Bedir et al. 2000b), belonging to Sect. Vulneraria, includes only flavonol glycosides. Amusingly, no cycloartane- or oleanane-type triterpene glycoside, the main constituents of Astragalus spp., was isolated from A. lycius and A. vulneraria. This peculiar feature characterizes a very limited group of Astragalus spp. (Guzhva et al. 1984, 1992).

Cycloastragenol with 20(R),24(S)-epoxy side chain is the principal aglycone in the Astragalus species along with cyclocanthogenol. However, cyclocephalogenol is more uncommon in the genus so far reported only from four sections, viz., Acanthophace [A. hareftae (Horo et al. 2012), A. icmadophilus (Horo et al. 2010)], Adiaspastus [A. aureus (Gülcemal et al. 2011)], Pterophorus [A. trojanus (Bedir et al. 1999a, b, 2001a), A. wiedemannianus Fischer (Polat et al. 2010)], and Rhacophorus [A. microcephalus (Bedir et al. 1998a, b), A. plumosus var. krugianus (Denizli et al. 2014), A. zahlbruckneri (Çalış et al. 2001)]. A. angustifolius (Gülcemal et al. 2012), single studied species of Melanocercis section, provided the C-24 epimer of cycloastragenol as aglycone, which was reported for the first time in nature. A. halicacabus (Djimtombaye et al. 2013), single tested species of Halicacabus section, provided maltol glycosides, reported for the first time in the Astragalus genus and even in the Fabaceae family. A. pennatulus (Un et al. 2016), belonging to Sect. Rhacophorus, provided a cyclocephalogenin-alike glycoside characterized by the deficiency of the hydroxyl function at C-6 and the presence of a keto function at C-24, so far never reported in literature.

Structural Summary of Cycloartanes

Astragalus cycloartanes are classified based on the side chains extending from C-17 of the tetracyclic framework. In the case of Turkish Astragalus cycloartanes, three main aglycone structures including cycloastragenol, cyclocanthagenol, and cyclocephalogenol have been reported, deriving from 20,24-epoxy-, acyclic-, and 20,25-epoxy side chains, respectively (Isaev et al. 1983a, b, 1989; Isaev 1991, 1995, 1996; Mamedova and Isaev 2004).

20,24-Epoxy Side Chain Compounds

As shown in Fig. 1, 20,24-epoxy side chain cycloartanes undergo both oxidation and glycosylation reactions at different positions during biosynthesis. Carbons 3, 6, 16, 23, and 25 are susceptible to oxidation reactions, mainly involving regio- and stereo-specific hydroxylations catalyzed by P450 monooxygenase enzymes. In the case of glycosylation reactions, except C-23 position, all of the hydroxylated carbons (3, 6, 16, and 25) were found to be sugar attached. Particularly, bisdesmosidic saponins are common in Astragalus cycloartanes, where C-3(O) and C-6(O) are the major attachment positions. Moreover, in nature, tridesmosidic saponins have only been reported from Astragalus species as cycloartane saponins (i.e., astragaloside VII, brachyoside C, cephalotoside A, trojanoside B, D, E, and F), whereas monodesmosidic and monosaccharidic compounds are encountered rarely compared to their counterparts bisdesmosidic/disaccharidic and trisaccharidic glycosides. Sugar diversity of the cycloartane class is much less in comparison to other saponin groups, such as oleananes, ursanes, lupanes, dammaranes, etc. Up to now, only six different sugar moieties have been found, viz., β-d-glucose, β-d-glucuronic acid, β-d-xylose, α-l-rhamnose, α-l-arabinose, and β-d-apiose. Although all the sugars mentioned above are found to be at C-3(O) position of 20,24-epoxy side chain cycloartanes, β-d-glucose is the only extending saccharide from C-16(O) and C-25(O) positions. Both β-d-glucuronic acid and β-d-xylose units have only been reported at C-6(O) position. While C-3(O) is found to include mono- or disaccharidic units, C-6, C-16, and C-25 positions are only glycosylated with a single sugar.
Fig. 1

General structure of 20,24-epoxy side chain compounds

Acyclic Side Chain Compounds

Acyclic side chain derivatives have also been reported with similar oxidation and glycosylation patterns shown in Fig. 2. Whereas oxidations (mainly hydroxylations) are observed at C-1, C-3, C-6, C-7, C-16, C-20, C-24, and C-25, the glycosylation occurs on oxygenated carbons 3, 6, 16, 24, and 25. All glycosylated carbons are found to have at least one sugar unit. However, C-3(O) goes under further glycosylation reactions yielding di- and trisaccharidic sugar chains, whereas disaccharidic nature was also encountered for C-24(O). The sugars reported to be attached on acyclic side chain cyloartanes are β-d-glucose, β-d-glucuronic acid, β-d-xylose, α-l-rhamnose, and α-l-arabinose. As in 20,24-epoxy side chain structures, C-3 was found to contain all abovementioned sugar moieties attached, whereas, except arabinose unit, all the sugars were reported from the major glycosylation position C-6. C-16 had only β-d-glucose, while β-d-glucose and β-d-xylose units were branching from C-24 and C-25 positions. β-d-Glucose was recorded in all sugar sites, whereas the sugar α-l-rhamnose extended only from C-3 and C-24
Fig. 2

General structure of acyclic side chain compounds

.

20,25-Epoxy Side Chain Compounds

20,25-Epoxy side chain cycloartanes are less common compared to the other side chains. This group of compounds is reported to have similar oxidation and glycosylation arrangement shown in Fig. 3. While hydroxylations are observed at C-3, C-6, C-16, and C-24, the glycosylation takes place on oxymethine carbons 3, 6, and 24. Up to now, five different sugars, viz., β-d-glucose, β-d-glucuronic acid, β-d-xylose, α-l-rhamnose, and α-l-arabinose, have been reported for 20,25-epoxy side chain cycloartanes. C-6(O) and C-24(O) are found to have monosaccharidic units, while C-3(O) locates mono-, di-, and tetrasaccharidic sugar chains. Only β-d-glucose or β-d-xylose are attached from C-6(O), whereas β-d-glucose is reported as the only sugar branching from C-24(O).
Fig. 3

General structure of 20,25-epoxy side chain compounds

Stereochemistry of Astragalus Cycloartanes

A total of 14 structurally distinct genins have been found in Turkish Astragalus species. Some of these have not been characterized as pure compounds but as the corresponding glycosides. β-Configuration of C-3 (OH) and C-16 (OH) and α-conuration of C-6 (OH) are consistent with all naturally occurring cycloartanes present in the genus Astragalus (Fig. 4).
Fig. 4

Stereochemistry of Astragalus cycloartanes

20,24-Epoxycycloartanes, representing the largest group in Turkish Astragalus plants, are found in nature with three different stereoisomers, viz., 20R,24S, 20S,24R and 20R,24R. In the case of 20S,24R configuration, C-20 and C-24 resonate about 86.5–87.5 and 84.5–85.5, respectively, while, for the 20R,24S configuration, these carbons have chemical shifts of ca. 87.0–88.0 and 81.5–82.5. For 20R,24R configuration, C-20 and C-24 resonate around 87.3–88.8 and 88.4–85.5, respectively (Kitagawa et al. 1983a; Bedir et al. 2001b; Gülcemal et al. 2012). 16β,24;20,24-Diepoxycycloartane-type derivatives are very unusual in the plant kingdom. An examination of molecular models indicates that the heterocycles can be fused as the 20R, 24R and 20S, 24S configurations. Therefore, establishing the stereochemistry of one of these asymmetric centers defines the configuration of the other chiral atom (Çalış et al. 2008b).

For the acyclic side chain substituted cycloartane-type saponins, obtained from the Astragalus genus, the 24-position locates a hydroxyl group, meaning two possible stereoisomer (24S or 24R). The 13C NMR chemical shift of C-24 could be used as a characteristic parameter in the determination of the configurations at C-24. In the case of the 24R configuration, the chemical shift of C-24 was found about 79.9–80.6 ppm (Isaev et al. 1983b), while for the 24S configuration of cyclocanthogenin, the same position’s chemical shift ranged between 77.0 and 78.2 ppm (Isaev et al. 1992).

20,25-Epoxycycloartane genins are represented only with a single stereoisomer of cyclocephalogenin (20R,25-epoxycycloartane). The α orientation of the -OH group at C-24 can be determined by the nOe correlation between Me-27 and H-24β signals (Bedir et al. 1998a).

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Faculty of Science, Department of ChemistryEge UniversityBornovaTurkey
  2. 2.Faculty of Engineering, Department of BioengineeringEge UniversityBornovaTurkey
  3. 3.Faculty of Engineering, Department of BioengineeringIzmir Institute of TechnologyUrlaTurkey

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