Rising trends towards the development of oral herbal male contraceptive: an insight review

Abstract

Background

Acknowledging population control to be an essential step for global health promotes wide research study in the area of male contraception. Although there are a great number of synthetic contraceptives available in the market, they have plenty of adverse effects. Different potential strategies for male contraception were investigated over a long period time consisting of hormonal, chemical, and immunological interventions, although these methods showed good antifertility results with low failure rates relative to condoms.

Main text

This review is based upon the concept of herbal contraceptives which are an effective method for controlling the fertility of animals and humans. This review has highlighted herbal medicinal plants and plant extracts which have been reported to possess significant antifertility action in males. The review considers those plants which are used traditionally for their spermicidal and antispermatogenic activities and imbalance essential hormones for fertility purposes and plants with reported animal studies as well as some with human studies for antifertility effect along with their doses, chemical constituents, and mechanism of action of the antifertility effect of the plants. This review also explains the phases of sperm formation, hormone production, and the mechanism of male contraceptives.

Conclusion

As far as the relevance of the current review is discussed, it might be quite useful in generating monographs on plants and recommendations on their use. A lot of the plant species listed here might appear promising as effective alternative oral fertility-regulating agents in males. Therefore, significant research into the chemical and biological properties of such less-explored plants is still needed to determine their contraceptive efficacy and also to possibly define their toxic effects so that these ingredients can be utilized with confidence to regulate male fertility. The new inventions in this field are necessary to concentrate on modern, more potent drugs with less harmful content and that are self-administrable, less costly, and entirely reversible.

Background

Today, overpopulation is a matter of extreme concern for developed nations along with developing countries [1, 2]. In the year 2011, the world population was estimated at 6,928,198,253 and increasing rapidly at a rate of 83 million citizens per year [3]. Among developing countries, India is densely populated and it is estimated that it will reach about 9.2 billion by the year 2050 [1, 2]. The year 2012 witnessed population figures reaching 1,210,193,422 [1] with an increment of 18 million to the total population every year [2]. According to India’s population in 2019, figures are 1,372,717,495 [4]. Increasing population leads to an increase in the demand for resources like water and food, starvation, malnutrition, and consumption of natural resources. Since natural resources are limited, control of the increasing population is a mandatory step [5]. Family planning is an easy and important tool for controlling population burden [6]. On other hand, in the USA, the unwanted pregnancy rate is approximately 45% with the help of the various contraceptive options provided to women [7]. Although female contraceptives are much effective in preventing unplanned pregnancy, giving high yielding results, it cannot be used by a greater proportion of sex due to their profuse adverse effects [8].

Talking about extreme measures, the World health Organization has initiated a population control program that includes trials linked to traditional medical activities [2]. Many methods for induction of infertility are implemented over a long period that involves biochemical, biological, and immunological pathways [9] with the least impact but minimal inadequacy [5]. During ancient times, the human reproduction system was not fully established. Hence, the progress in research could not be put into practice due to unclear mechanisms related to human hormones [10].

Main text

Methods and materials

The present study has been geared up with wide-ranging facts of curative plants inhabiting all over the world concerning their accepted tradition by countless ethnic groups for fertility regulation in males. To date, no examination has analyzed the dose, constituents of elements, and mechanism of action of the antifertility effect of plants.

So, information concerning this article has been systematically gathered from the sources of scientific literature, including PubMed, Google Scholar, Science Direct, and Scopus. Simply applicable studies available in the English language were considered. The botanical and English names are considered after validation from available text and database. The criteria followed for the choice of information in this evaluation deliberate folk plant:

  1. 1.

    Found in Ancient Indian medicines

  2. 2.

    With recorded animal studies for effects on infertility as well as those with human studies of antifertility effect

Plants, their parts, or their extracts traditionally used for spermicidal and antispermatogenic activities and those that imbalance essential hormones for fertility purposes have been considered as antifertility agents. Furthermore, compounds isolated from plants with attributed potential for fertility regulation are also classified into 6 categories:

  1. 1.

    Phytoconstituents with spermicidal activity

  2. 2.

    Phytoconstituents with antispermatogenic activity

  3. 3.

    Phytoconstituents acts through Sertoli cells

  4. 4.

    Phytoconstituents acts through Leydig cells

  5. 5.

    Phytoconstituents with antimotility activity

  6. 6.

    Phytoconstituents acts by unbalancing hormones

The following keywords were used to search the literature in the data sources: oral male contraceptives, herbal contraceptives, antifertility, and male contraception.

The need of male contraceptives-a boon for society!!!

Acknowledging population control to be an essential step for global health promotes an opportunity for a large-scale research study in the field of male contraceptives [11]. Male contraceptives originated with the use of a condom in ancient times in Imperial Rome. Researches on male contraception initiated with the sole objective of taking easy targets to the male reproductive system by stopping either the sperm or the testis to function [10]. Although there are a great number of synthetic contraceptives available in the market, they have plenty of adverse effects [5].

Moreover, there is a rise in the need for male contraceptives to avoid unwanted pregnancies because not many men wish to take responsibility for family planning [8]. Also due to the adverse effects of synthetic male contraceptives, the quest for a modern, more effective, more reliable, and less expansive approach is the priority as well as objectives for the pharmaceutical and medical sciences not to forget an unusual self-administration and long-lasting effect of male contraceptives [9]. The new inventions in this field often concentrate on modern, more potent drugs with less harmful content and that are self-administrable, less costly, and entirely reversible [12].

Why not herbals???

Since ancient times, plants are always regarded as a potent source of nourishment that we require for staying healthy along with their valuable components commonly used for food and nutrition, beverages, cosmetics, dyes, medicines, etc. Herbs are excellent examples of being one of the richest sources of nutrients that aim at protecting and restoring a healthy life [13]. As specified by the World Health Organization (WHO) statistics, almost 65–80% of the world’s population relies on plant species and their health care products due to the lack of modern facilities and poor conditions. There is a total of 422,000 plant species that have been recorded all over the world, out of which 20,000 species are acclaimed as wild edible species and less than 20,000 of the same community is consumed as a food supplement for 90% of people around the world, contributing to almost 25% of drug formulations from plants or their extracts [14]. The herbal preparations have been used as an oral tradition. It is becoming more popular and useful in modern times as demand for natural remedies/medicines is increasing every day because of the belief of people that they do not have any adverse effects, a boon in disguise [15]. Continuing the traditional system of medicines, more than 35,000 plant species are being used worldwide for medicinal purposes. Following which, more than 80% of the world population is turning to herbal preparations that contain plant extracts for primary health care [2].

Herbal contraceptives are plant-based contraceptives which are effective methods for controlling the fertility of animals and humans [16]. The chemical constituents of plants such as flavonoids, terpenes, tannins, quinines, diterpenoids, and lactones are apprehended to possess antifertility action through a different mechanism [17]. Different potential mechanisms for male contraception have been studied over a long period of time consisting of hormonal, chemical, and immunological strategies [2, 18] though these methods have shown better results of antifertility effects with minimum failure rates than condoms.

In recent years, plants have been reported to be used in the regulation of male fertility because of the better compatibility with the human body, better cultural acceptability, and lesser adverse effects giving it an upper hand [19]. As a result, herbal products attract scientists as a primary source of naturally occurring antifertility agents due to little or negligible adverse signs [17]. For instance, in India, several herbal plants have been reported to have antifertility effects that act through the mechanism by suppression of spermatogenesis or by prevention of implantation [20].

Phases for sperm formation

Testicular carries out two primary goals:

  1. 1.

    Testosterone production

  2. 2.

    Spermatogenesis (origin of haploid germ cells) [8] (Fig. 1)

Fig. 1
figure1

Different phases by which sperm formation takes place

Flow sheet for production of hormones [21] (Fig. 2)

Pituitary gonadotrophins regulate the functions of the testicles, with luteinizing hormones (LH) acting on the testosterone and producing interstitial cells and the follicle-stimulating hormone (FSH) affecting the cells of the seminiferous tubules. Including the seminiferous epithelium’s structural elements, the movement of nutritional growth factor to the haploid germ cells with a near junction in the epithelium for consecutive cells is known as the “blood-testis barrier.” Well-performing Sertoli cells supply sufficient mitogens, distinct factors, and energy sources to the growing germ cell, as well as shielding them from the host’s own immune system from harmful agents. The number and function of the present Sertoli cells define the spermatogenesis rate and quality [22].

Fig. 2
figure2

Release and production of different hormones from glands

Male contraceptives might work as follows:

  1. 1.

    Suppress sperm production by antispermatogenic

  2. 2.

    Prevention of maturation of sperm

  3. 3.

    Prevention of the flow of sperm through vas deferens

  4. 4.

    Prevention of deposition of the sperm [1]

Phytoconstituents with spermicidal agents

Ideal spermicidal characteristics include the following: would rapidly and irreversibly achieve sperm immobilization, are not harmful to the vaginal and penile mucosa, do not have any side effects on the growing fetus that are free from long-term topical and systemic toxicity, and should not be ingested systemically [23]. A typical lipid bilayer consisting of outer, intra, and transmembrane proteins is a key component of the plasma membrane of sperms. This lipid bilayer associate with saponin molecules, impacting cell membrane glycoproteins and altering ionic movement across the membrane, resulting in many plants (Phytolacca dodecadra, Calendula officinalis, and Acacia caesia) differing [24]. Sperm immobilization can be caused by the acid pH of lemon juice through the denaturation of ATPase dyein [23].

Phytoconstituents with antispermatogenic activity

The spermatogenesis process involves a complex process:

  1. 1.

    Spermatocytogenesis

  2. 2.

    Spermatidogenesis

  3. 3.

    Spermiogenesis

A diploid spermatogonium undergoes mitotic division in the process of spermatocytogenesis and develops two diploids known as primary spermatocytes. Every primary spermatocyte divides into two haploid secondary spermatocytes by meiosis. Spermiogenesis is the process of spermatid differentiation into mature sperm. It indicates interference in the steroidogenesis when the cholesterol level rises and sudanophilic lipid accumulates [25].

Phytoconstituents acts through Sertoli cells

Sertoli cells are columnar with oval or pear nuclei and thin mitochondria; at the base of their cytoplasm, they have lipofuscin and lipid droplets. The main feature of Sertoli cell structural support for germ cell development is the blood test barrier, which is situated between neighboring Sertoli cells in close junctions. Sertoli cells play an important part in the process of spermatogenesis and adult life as a whole. The plant extracts kill the viability and work of Sertoli cells and have various effects on spermatogenesis, such as reducing the nuclear and cytoplasmic volume and vacuolizing Sertoli cells [26].

Phytoconstituents acts through Leydig cells

Leydig cells are polyhedral with a large prominent nucleus, an eosinophilic cytoplasm, and various vesicles packed with lipids. The hormone-releasing gonadotropin, secreted and synthesized by the hypothalamus, produces and releases LH and FSH from the pituitary gland. LH induces the production of testosterone in the testis Leydig cells [27].

Phytoconstituents with antimotility activity

The sperm passes through three sections of the caput, corpus, and cauda epididymis that are important for sperm maturation [28]. Therefore, the production and secretion of proteins through the epididymis and the completion of various morphological, biochemical, and motile properties during the transformation from epididymis are important for the spermatozoa’s full capacity to fertilize [29].

Phytoconstituents acts by unbalancing hormone

Hypothalamus, pituitary gland, and testis secrete the various hormones which regulate spermatogenesis [30]. The Leydig cells synthesize and secrete the major male sex hormone testosterone under the influence of pituitary gonadotropin luteinizing hormone (LH). Several plant products are considered to contain enzymes that are used in androgen synthesis [31]. Quassia Amara’s blunt methanol extract shows lower levels of testosterone, LH, and hormone-stimulating follicles (Fig. 3) (Table 1)

Fig. 3
figure3

Isolated compounds from plants having antifertility activity

Table 1 List of traditional plants and isolated chemical compounds from plants having antifertility activity

Epidemiological studies have shown that the use of combination oral contraceptives increases the possibility of brain thrombosis; enhances the serum triglyceride, high-density lipoprotein (HDL), and cholesterol levels; and also increases family mortality related to cardiovascular diseases as well as malignant tumors in any organ, low resistance to glucose or insulin, diarrhea, abdominal pain, fatigue, hypertension, and menstrual shifts [2].

Patents available are shown Table 2.

Table 2 List of patents on a male contraceptive

Conclusion

Different potential strategies for male contraception were investigated over a long period time consisting of hormonal, chemical, and immunological interventions, although these methods showed good antifertility results with low failure rates relative to condoms. The present study showed the literature data that there is majority of plants, which are traditionally used as antifertility agents and their effects have not been thoroughly studied on animals. The majority of tests have been performed on conscious animals and relatively few tests have had their efficacy confirmed in humans. Herbal contraceptives are safer and cheaper methods for population overcoming. To summarize, a lot of the plant species listed here might appear promising as effective alternative oral fertility-regulating agents in males. Among plant parts, leaves have been maximally utilized for controlling fertility. As far as the relevance of the current review is discussed, it might be quite useful in generating monographs on plants and recommendations on their use. Therefore, this review has highlighted the significant antifertility activity of herbal medicinal plants and their extracts. Moreover, this review can concentrate the interest of researchers on toxicity studies of phytoconstituents and their clinical trials, which may serve as an alternate potential antifertility agents with milder or fewer side effects and can be developed into suitable contraceptive formulations. Therefore, significant research into the chemical and biological properties of such less-explored plants is still needed to determine their contraceptive efficacy and also will possibly define their toxic effects so that these ingredients can be utilized with confidence to regulate male fertility.

Availability of data and materials

All the information in the manuscript has been referred from the included references and is available upon request from the corresponding author.

Abbreviations

LH:

Luteinizing hormones

FSH

Follicle-stimulating hormone

HDL

High-density lipoprotein

B.W.

Body weight

References

  1. 1.

    Soni PK, Luhadia G, Sharma DK, Mali PC (2015) Antifertility activates of traditional medicinal plants in male with emphasis on their mode action: a review. J Glob Biosci 4:1165–1179

    Google Scholar 

  2. 2.

    Kaur R, Sharma A, Kumar R, Kharb R (2011) Rising trends towards herbal contraceptives. J Nat Prod Plant Resour 1:5–12

    Google Scholar 

  3. 3.

    Harisha B, Swamy VB (2012) Evaluation of antifertility activity of Melothria heterophylla (Lour.) Cogn. Res J Pharma Bio Chem Sci 3:754–771

    Google Scholar 

  4. 4.

    India population web search, dated: 26 January, 2020 http://worldpopulationreview.com/countries/india-population/

  5. 5.

    Singh R, Kakar S, Shah M, Jain R (2018) Some medicinal plants with anti-fertility potential: a current status. J Basic Clin Reprod Sci 7:7–19

    Google Scholar 

  6. 6.

    Ghosh P, Gupta P, Tripathy A, Das B, Ghosh D (2018) Evaluation of hypotesticular activities of different solvent fractions of hydro-methanolic extract of the fruit of Terminalia chebula in Wistar strain adult albino rat: genomic and flow cytometric approaches. J Appl Biomed 16:394–400

    Article  Google Scholar 

  7. 7.

    Long JE, Lee MS, Blithe DL (2019) Male contraceptive development: update on novel hormonal and nonhormonal methods. Clin Chem 65:153–160

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  8. 8.

    Amory JK (2016) Male contraception. Fertil Steril 106:1303–1309

    PubMed  PubMed Central  Article  Google Scholar 

  9. 9.

    Gupta RS, Sharma R (2006) A review on medicinal plants exhibiting antifertility activity in males. Nat Prod Rad 5:389–310

    Google Scholar 

  10. 10.

    Michael GO, Silva EJ, Hamil KG (2016) Non-hormonal male contraception: a review and development of an Eppin based contraceptive. Pharmacol Ther 157:105–111

    Article  CAS  Google Scholar 

  11. 11.

    Afzalzadeh MR, Ahangarpour A, Amirzargar A, Varnamkhasti MK, Ganjalidarani H (2015) The effect of Vitis vinifera L. juice on serum levels of inhibin B, sperm count in adult male rats. World J Mens Health 33:109–116

    PubMed  PubMed Central  Article  Google Scholar 

  12. 12.

    Bhattacharya P, Saha A (2013) Evaluation of reversible contraceptive potential of Cordia dichotoma leaves extract. Rev Bras Farmacogn 23:342–350

    Article  Google Scholar 

  13. 13.

    Tripathy B, Swain SN, Panda MK, Pradhan RN, Acharya UR (2018) Antispermatogenic effects of seed extract of Caesalpinia bonducella in Swiss mice. Int J Biosci 12:23–34

    CAS  Article  Google Scholar 

  14. 14.

    Zaman W, Ahmad M, Zafar M, Amina H, Ullah F, Bahadur S, Ayaz A, Saqib S, Begum N, Jahan S (2020) The quest for some novel antifertility herbals used as male contraceptives in district Shangla, Pakistan. Acta Ecol Sin 40:102–112. https://doi.org/10.1016/j.chnaes.2019.05.017

    Article  Google Scholar 

  15. 15.

    Rajan TS, Sarathchandiran I, Kadalmani B (2013) Evaluation of newly developed herbal oral suspension for spermatotoxic activity on male Wistar albino rats. J Pharm Res 7:347–351

    Google Scholar 

  16. 16.

    Sitasiwi AJ, Isdadiyanto S, Mardiati SM (2018) Effect of ethanolic Neem (Azadirachta indica) leaf extract as an herb contraceptive on Hepato-somatic Index of the male mice (Mus musculus). J Phys Conf Ser 1025:012043

    Article  CAS  Google Scholar 

  17. 17.

    Zaman W, Shah SN, Ullah F, Ayaz A, Ahmad M, Ali A (2019) Systematic approach to the correct identification of Asplenium dalhousiae (Aspleniaceae) with their medicinal uses. Microsc Res Tech 82:459–465

    PubMed  Article  PubMed Central  Google Scholar 

  18. 18.

    Khillare B, Shrivastav TG (2003) Spermicidal activity of Azadirachta indica (neem) leaf extract. Contraception 68:225–229

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  19. 19.

    Singh N, Singh SK (2016) Citrus limon extract: possible inhibitory mechanisms affecting testicular functions and fertility in male mice. Syst Biol Reprod Med 62:39–48

    PubMed  Article  PubMed Central  Google Scholar 

  20. 20.

    Chakraborty K, Pal S, Bhattacharya AK (2003) Sperm immobilization activity of Allium sativum L. and other plants extracts. Asian J Androl 5:131–135

    Google Scholar 

  21. 21.

    Sethi J, Yadav M, Sood S, Dahiya K, Singh V (2010) Effect of tulsi (Ocimum Sanctum Linn.) on sperm count and reproductive hormones in male albino rabbits. Int J Ayurveda Res 1:208–210

    PubMed  PubMed Central  Article  Google Scholar 

  22. 22.

    Petersen C, Söder O (2006) The sertoli cell–a hormonal target and ‘super’nurse for germ cells that determines testicular size. Horm Res Paediatr 66:153–161

    CAS  Article  Google Scholar 

  23. 23.

    Burgess SA, Walker ML, Sakakibara H, Knight PJ, Oiwa K (2003) Dynein structure and power stroke. Nature 421:715–718

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  24. 24.

    Nivsarkar M, Shrivastava N, Patel M, Padh H, Bapu C (2002) Sperm membrane modulation by Sapindus mukorossi during sperm maturation. Asian J Androl 92:233–235

    Google Scholar 

  25. 25.

    Mandal TK, Das NS (2010) Testicular toxicity in cannabis extract treated mice: association with oxidative stress and role of antioxidant enzyme systems. Toxicol Ind Health 26:11–23

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  26. 26.

    Sharma RS, Rajalakshmi M, Jeyaraj DA (2001) Current status of fertility control methods in India. J Biosci 26:391–305

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  27. 27.

    Dufau ML, Winters CA, Hattori M, Aquilano D, Baranao JL, Nozu K, Baukal A, Catt KJ (1984) Hormonal regulation of androgen production by the Leydig cell. J Steroid Biochem 20:161–173

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  28. 28.

    Sullivan R, Mieusset R (2016) The human epididymis: its function in sperm maturation. Hum Reprod Update 22:574–587

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  29. 29.

    Jahan S, Rasool S, Khan MA, Ahmad M, Zafar M, Arsahd M, Abbasi AM (2009) Antifertility effects of ethanolic seed extract of Abrus precatorius L. on sperm production and DNA integrity in adult male mice. J Med Plant Res 3:809–814

    Google Scholar 

  30. 30.

    Sofikitis N, Giotitsas N, Tsounapi P, Baltogiannis D, Giannakis D, Pardalidis N (2008) Hormonal regulation of spermatogenesis and spermiogenesis. J Steroid Biochem Mol Biol 109:323–330

    CAS  PubMed  Article  Google Scholar 

  31. 31.

    Coutinho EM, Athayde C, Atta G, Gu ZP, Chen ZW, Sang GW, Emuveyan E, Adekunle AO, Mati J, Otubu J, Reidenberg MM (2000) Gossypol blood levels and inhibition of spermatogenesis in men taking gossypol as a contraceptive: a multicenter, international, dose-finding study. Contraception 61:61–67

    CAS  PubMed  Article  Google Scholar 

  32. 32.

    Pakrashi A, Ray H, Pal BC, Mahato SB (1991) Sperm immobilizing effect of triterpene saponins from Acacia auriculiformis. Contraception 43:475–483

    CAS  PubMed  Article  Google Scholar 

  33. 33.

    Chauhan A, Agarwal M (2008) Reversible changes in the antifertility induced by Aegle marmelos in male albino rats. Syst Biol Reprod Med 54:240–246

    CAS  PubMed  Article  Google Scholar 

  34. 34.

    Shyamlal YS, Jaiswal M, Prajapati PK (2012) Therapeutic potentials of Shirisha (Albizia lebbeck Benth)–a review. Int J Ayurvedic Med 2:153–163

    Google Scholar 

  35. 35.

    Pankajakshy A, Madambath I (2009) Spermatotoxic effects of Cananga odorata (Lam): a comparison with gossypol. Fertil Steril 91:2243–2246

    PubMed  Article  Google Scholar 

  36. 36.

    Souad K, Ali S, Mounir A, Mounir TM (2007) Spermicidal activity of extract from Cestrum parqui. Contraception 75:152–156

    PubMed  Article  Google Scholar 

  37. 37.

    Kumar S, Biswas S, Mandal D, Roy HN, Chakraborty S, Kabir SN, Banerjee S, Mondal NB (2007) Chenopodium album seed extract: a potent sperm-immobilizing agent both in vitro and in vivo. Contraception 75:71–78

    PubMed  Article  Google Scholar 

  38. 38.

    Yakubu MT, Akanji MA, Oladiji AT (2007) Evaluation of antiandrogenic potentials of aqueous extract of Chromolaena odoratum (L.) KR leaves in male rats. Andrologia 39:235–243

    CAS  PubMed  Article  Google Scholar 

  39. 39.

    Gupta RS, Yadav RK, Dixit VP, Dobhal MP (2001) Antifertility studies of Colebrookia oppositifolia leaf extract in male rats with special reference to testicular cell population dynamics. Fitoterapia 72:236–245

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  40. 40.

    Shkukani HG, Salhab AS, Disi AM, Shomaf MS, Quadan FA (2008) Antifertility effect of ethanolic extract of Juniperus phoenica (L.) in male albino rats. J Herb Pharmacother 7:179–189

    Article  Google Scholar 

  41. 41.

    Rajasekaran M, Nair AG, Hellstrom WJ, Sikka SC (1993) Spermicidal activity of an antifungal saponin obtained from the tropical herb Mollugo pentaphylla. Contraception 47:401–412

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  42. 42.

    Raji Y, Bolarinwa AF (1997) Antifertility activity of Quassia amara in male rats—in vivo study. Life Sci 61:1067–1074

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  43. 43.

    Srivastav A, Chandra A, Singh M, Jamal F, Rastogi P, Rajendran SM, Bansode FW, Lakshmi V (2010) Inhibition of hyaluronidase activity of human and rat spermatozoa in vitro and antispermatogenic activity in rats in vivo by Terminalia chebula, a flavonoid rich plant. Reprod Toxicol 29:214–224

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  44. 44.

    Gupta RS, Sharma A (2003) Antifertility effect of Tinospora cordifolia (Willd.) stem extract in male rats. Indian J Exp Biol 41:885–889

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Dubey R, Dubey K, Sridhar C, Jayaveera KN (2011) Sperm immobilization activity of aqueous, methanolic and saponins extract of bark of Ziziphus Mauritiana. Der Pharm Sin 2:11–16

    CAS  Google Scholar 

  46. 46.

    Singh A, Singh SK (2009) Evaluation of antifertility potential of Brahmi in male mouse. Contraception 79:71–79

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  47. 47.

    Verma PK, Sharma A, Joshi SC, Gupta RS, Dixit VP (2005) Effect of isolated fractions of Barleria prionitis root methanolic extract on reproductive function of male rats: preliminary study. Fitoterapia 76:428–432

    PubMed  Article  PubMed Central  Google Scholar 

  48. 48.

    Sailani MR, Moeini H (2007) Effect of Ruta graveolens and Cannabis sativa alcoholic extract on spermatogenesis in the adult wistar male rats. Indian J Urol 23:257–260

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  49. 49.

    Onyeka CA, Aligwekwe AU, Olawuyi TS, Nwakanma AA, Kalu EC, Oyeyemi AW (2012) Antifertility effects of ethanolic root bark extract of Chrysophyllum albidum in male albino rats. Int J Appl Res Nat Prod 5:12–17

    Google Scholar 

  50. 50.

    Mali PC, Chaturvedi M, Ansari AS, Dixit VP (2001) Antispermatogenic effects of an ethanol extract of Citrullus colocynthis root in male albino rats. Pharm Biol 39:113–119

    Article  Google Scholar 

  51. 51.

    Vijaykumar B, Sangamma I, Sharanabasappa A, Patil SB (2004) Antispermatogenic and hormonal effects of Crotalaria juncea Linn. seed extracts in male mice. Asian J Androl 6:67–70

    CAS  PubMed  PubMed Central  Google Scholar 

  52. 52.

    Muthu K, Krishnamoorthy P (2011) Antifertility activity of methanolic extract of Cuminum cyminumin seed on male albino rats. Int J Genet Eng Biotech 2:205–214

    Google Scholar 

  53. 53.

    Mishra RK, Singh SK (2009) Reversible antifertility effect of aqueous rhizome extract of Curcuma longa L. in male laboratory mice. Contraception 79:479–487

    PubMed  Article  PubMed Central  Google Scholar 

  54. 54.

    Yakubu MT, Akanji MA, Oladiji AT (2008) Effects of oral administration of aqueous extract of Fadogia agrestis (Schweinf. Ex Hiern) stem on some testicular function indices of male rats. J Ethnopharmacol 115:288–292

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  55. 55.

    Jana TK, Das S, Ray A, Mandal D, Giri Jana S, Bhattacharya J (2013) Study of the effects of hibiscusrosa-sinensis flower extract on the spermatogenesis of male albino rats. J Physiol Pharmacol Adv 3:167–171

    Article  Google Scholar 

  56. 56.

    Gonzales GF, Ruiz A, Gonzales C, Villegas L, Cordova A (2001) Effect of Lepidium meyenii (maca) roots on spermatogenesis of male rats. Asian J Androl 3:231–233

    CAS  PubMed  PubMed Central  Google Scholar 

  57. 57.

    Bayala B, Telefo PB, Bassole IHN, Tamboura HH, Belemtougri RG, Sawadogo L, Malpaux B, Dacheux JL (2011) Anti-spermatogenic activity of Leptadenia hastata (Pers.) Decne leaf stems aqueous extracts in male wistar rats. J Pharmacol Toxicol 6:391–399

    Article  Google Scholar 

  58. 58.

    Naseem MZ, Patil SR, Patil SR, Patil SB (1998) Antispermatogenic and androgenic activities of Momordica charantia (Karela) in albino rats. J Ethnopharmacol 61:9–16

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  59. 59.

    Watcho P, Donfack MM, Zelefack F, Nguelefack TB, Wansi S, Nguola F, Kamtchouing P, Tsamo E, Kamanyi A (2005) Effects of the hexane extract of Mondia whitei on the reproductive organs of male rat. Afr J Tradit Complement Altern Med 2:302–311

    Article  Google Scholar 

  60. 60.

    Raji Y, Akinsomisoye OS, Salman TM (2005) Antispermatogenic activity of Morinda lucida extract in male rats. Asian J Androl 7:405–410

    PubMed  Article  PubMed Central  Google Scholar 

  61. 61.

    Etta HE, Bassey UP, Eneobong EE, Okon OB (2009) Anti-spermatogenic effects of ethanol extract of Mucuna urens. J Reprod Contracept 20:161–168

    Article  Google Scholar 

  62. 62.

    Obianime AW, Aprioku JS, Esomonu CT (2010) Antifertility effects of aqueous crude extract of Ocimum gratissimum L. leaves in male mice. J Med Plant Res 4:809–816

    Google Scholar 

  63. 63.

    Gupta RS, Rehwani H, Khushalani V, Tanwar K, Joshi YC (2007) Antispermatogenic effects of Parkinsonia aculeata stem bark in male rats. Pharm Biol 45:1–8

    CAS  Article  Google Scholar 

  64. 64.

    Mishra RK, Singh SK (2009) Antispermatogenic and antifertility effects of fruits of Piper nigrum L. in mice. Indian J Exp Biol 47:706–714

    PubMed  PubMed Central  Google Scholar 

  65. 65.

    Khouri NA, El-Akawi Z (2005) Antiandrogenic activity of Ruta graveolens L in male Albino rats with emphasis on sexual and aggressive behavior. Neuroendocrinol Lett 26:823–829

    PubMed  PubMed Central  Google Scholar 

  66. 66.

    Sharma A, Verma PK, Dixit VP (2003) Effect of Semecarpus anacardium fruits on reproductive function of male albino rats. Asian J Androl 5:121–124

    PubMed  PubMed Central  Google Scholar 

  67. 67.

    Sharangouda JP, Satishagouda S, Vishwanatha T, Saraswati B (2010) Effect of terminalia bellirica barks extracts on activities of accessory reproductive ducts in male rats. Int J Pharm Sci Rev Res 1:75–79

    Google Scholar 

  68. 68.

    Gupta R, Kachhawa JB, Gupta RS, Sharma AK, Sharma MC, Dobhal MP (2011) Phytochemical evaluation and antispermatogenic activity of Thevetia peruviana methanol extract in male albino rats. Hum Fertil 14:53–59

    CAS  Article  Google Scholar 

  69. 69.

    Aladakatti RH, Ahamed RN (2005) Changes in Sertoli cells of albino rats induced by Azadirachta indica A. Juss leaves. J Basic Clin Physiol Pharmacol 16:67–80

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  70. 70.

    Gupta RS, Kachhawa JB, Sharma A (2008) Effect of methanolic extract of Dendrophthoe falcata stem on reproductive function of male albino rats. J Herb Pharmacother 7:1–3

    Article  Google Scholar 

  71. 71.

    Krishnamoorthy P, Vaithinathan S (2003) Effect of the extract of Thespesia populnea leaves on mice testis. J Environ Biol 24:327–330

    CAS  PubMed  PubMed Central  Google Scholar 

  72. 72.

    Zi-Jian L, Zhi-Ping G, Rong-Fa L, Lin-Zhi Z (1992) Effects of multiglycosides of Tripterygium wilfordii (GTW) on rat fertility and Leydig and Sertoli cells. Contraception 45:249–261

    Article  Google Scholar 

  73. 73.

    Gupta RS, Dixit VP (1989) Testicular cell population dynamics following palmitine hydroxide treatment in male dogs. J Ethnopharmacol 25:151–157

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  74. 74.

    Gupta RS, Sharma N, Dixit VP (1990) Calotropin–a novel compound for fertility control. Anc Sci Life 9:224–230

    CAS  PubMed  PubMed Central  Google Scholar 

  75. 75.

    Oluyemi KA, Jimoh OR, Adesanya OA, Omotuyi IO, Josiah SJ, Oyesola TO (2007) Effects of crude ethanolic extract of Garcinia cambogia on the reproductive system of male wistar rats (Rattus novergicus). Afr J Biotechnol 6:1236–1238

    Article  Google Scholar 

  76. 76.

    Chakraborty S, Pakrashi A (1991) Antifertility effect of chronically administered Malviscus conzattii flower extract on fertility of male rats. Contraception 43:273–285

    CAS  PubMed  Article  Google Scholar 

  77. 77.

    Mali PC, Ansari AS, Chaturvedi M (2002) Antifertility effect of chronically administered Martynia annua root extract on male rats. J Ethnopharmacol 82:61–67

    CAS  PubMed  Article  Google Scholar 

  78. 78.

    Lohiya NK, Manivannan B, Goyal S, Ansari AS (2008) Sperm motility inhibitory effect of the benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya in langur monkey, Presbytis entellus entellus. Asian J Androl 10:298–206

    PubMed  Article  Google Scholar 

  79. 79.

    Chaturvedi M (1995) Fertility regulation in male rats with the help of Echinops echinatus (Roxb) root extract. J Phytol Res 8:115–118

    Google Scholar 

  80. 80.

    Coutinho EM, Melo JF, Barbosa I, Segal SJ (1984) Antispermatogenic action of gossypol in men. Fertil Steril 42:424–430

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  81. 81.

    Saba AB, Oridupa OA, Oyeyemi MO, Osanyigbe OD (2009) Spermatozoa morphology and characteristics of male Wistar rats administered with ethanolic extract of Lagenaria Breviflora Roberts. Afr J Biotechnol 8:1170–1175

    Google Scholar 

  82. 82.

    Olatunji-Bello II, Ijiwole T, Awobajo FO (2009) Evaluation of the deleterious effects of aqueous fruit extract of Abelmoschus esculentus (okro fruit) on some male reproductive parameters in Sprague Dawley rats. J Phytol 1:461–468

    Google Scholar 

  83. 83.

    Sinha R (1990) Post-testicular antifertility effects of Abrus precatorius seed extract in albino rats. J Ethnopharmacol 28:173–181

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  84. 84.

    Yakubu MT, Afolayan AJ (2009) Reproductive toxicologic evaluations of Bulbine natalensis Baker stem extract in albino rats. Theriogenology 72:322–332

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  85. 85.

    Ashok P, Meenakshi B (2004) Contraceptive effect of Curcuma longa (L.) in male albino rat. Asian J Androl 6:71–74

    PubMed  PubMed Central  Google Scholar 

  86. 86.

    Takizawa T, Mitsumori K, Takagi H, Nasu M, Yasuhara K, Onodera H, Imai T, Hirose M (2004) Sequential analysis of testicular lesions and serum hormone levels in rats treated with a Psoralea corylifolia extract. Food Chem Toxicol 42:1–7

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  87. 87.

    Melis MS (1999) Effects of chronic administration of Stevia rebaudiana on fertility in rats. J Ethnopharmacol 67:157–161

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  88. 88.

    Mishra RK, Singh SK (2008) Safety assessment of Syzygium aromaticum flower bud (clove) extract with respect to testicular function in mice. Food Chem Toxicol 46:3333–3338

    CAS  PubMed  Article  PubMed Central  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

Not applicable.

Author information

Affiliations

Authors

Contributions

We declare that this work was done by the authors named in this article: SV conceived and designed the study. AY carried out the literature collection of the data and writing of the manuscript. AY and SV assisted in the data analysis and corrected the manuscript. The authors read and approved the final manuscript.

Corresponding authors

Correspondence to Surender Verma or Akash Yadav.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Verma, S., Yadav, A. Rising trends towards the development of oral herbal male contraceptive: an insight review. Futur J Pharm Sci 7, 23 (2021). https://doi.org/10.1186/s43094-020-00154-7

Download citation

Keywords

  • Antifertility
  • Family planning
  • Herbal contraceptives
  • Herbs
  • Mechanisms
  • Oral male contraceptives
  • Overpopulation