• Abstract

    The incidence of male infertility has increased dramatically in recent decades, and herbal medicine is a potential complementary treatment. Animal studies are essential to gain insights into the mechanisms involved and refine the development of herbal medicine in human trials. This study aimed to systematically review the protective effects of herbal medicines on murine spermatogenesis. A literature search was conducted using databases such as EMBASE, PubMed, and Google Scholar, as well as scientific journals indexed in the Web of Science, until October 21, 2024. The studies included in the analysis focused on the effects of herbal medicines on murine models, specifically examining physical and organ weights, reproductive parameters, metabolic and biochemical markers, oxidative stress, and antioxidant markers. The analysis included 48 studies from 44 articles involving 1597 murine subjects, 27 plant species, and seven formulations. Herbal medicine significantly increased male murine reproductive organ weights, including body weight (SMD = 1.83; 95% CI: 1.24, 2.42), testis weight (SMD = 1.94; 95% CI: 1.42, 2.46), relative testis weight (SMD = 2.01; 95% CI: 1.27, 2.75), epididymis weight (SMD = 1.22; 95% CI: 0.79, 1.65), relative epididymal weight (SMD = 1.93; 95% CI: 0.93, 2.93), seminal vesicle weight (SMD = 1.25; 95% CI: 0.75, 1.75), and relative seminal vesicle weight (SMD = 1.67; 95% CI: 0.81, 2.54). Additionally, treatment increased the seminiferous tubule diameter (SMD = 9.10; 95% CI: 4.93, 13.28) and Johnson's score (SMD = 6.40; 95% CI: 3.73, 9.06). In the injury models, the semen parameters, including sperm count (SMD = 3.47; 95% CI: 2.72, 4.21), motility (SMD = 3.57; 95% CI: 2.70, 4.44), viability (SMD = 2.04; 95% CI: 1.21, 2.87), and abnormal sperm morphology (SMD = -2.28; 95% CI: -3.65, -1.72), improved. Although no significant changes were observed in FSH and LH levels, the serum testosterone levels increased favorably. Moreover, blood serum biochemical parameters and oxidative stress markers in the injured mouse model were improved following herbal treatment. Herbal medicines have been shown to enhance spermatogenesis in murine models. These in-depth findings provide a foundation for optimizing future human studies.

  • References

    1. Alkhedaide, A., Alshehri, Z. S., Sabry, A., Abdel-Ghaffar, T., Soliman, M. M., & Attia, H. (2016). Protective effects of grape seed extract against cadmium-induced testicular dysfunction. Molecular Medicine Reports, 13, 3101–3109. https://doi.org/10.3892/mmr.2016.4928.
    2. Ambulkar, P. S., Sigh, R., Reddy, M., Varma, P. S., Gupta, D. O., Shende, M. R., & Pal, A. K. (2014). Genetic risk of Azoospermia Factor (AZF) microdeletions in idiopathic cases of azoospermia and oligozoospermia in Central Indian population. Journal of Clinical and Diagnostic Research, 8, 88–91. https://doi.org/10.7860/JCDR/2014/7680.4116.
    3. Aslan, E., Kumalar, K., Güzel, H., Demirel, H., Celik, S., & Pektas, M. (2021). Effects of Panax ginseng on cisplatin-induced testicular damage of rats. Anatolian Journal of Botany, 5. https://doi.org/10.30616/ajb.869240.
    4. Bahmanpour, S., Vojdani, Z., Panjehshahin, M. R., Hoballah, H., & Kassas, H. (2012). Effects of Carthamus tinctorius on semen quality and gonadal hormone levels in partially sterile male rats. Korean Journal of Urology, 53, 705–710.
    5. Balawender, K., & Orkisz, S. (2020). The impact of selected modifiable lifestyle factors on male fertility in the modern world. Central European Journal of Urology, 73, 563–568. https://doi.org/10.5173/ceju.2020.1975.
    6. Barratt, C. L. R., et al. (2017). The diagnosis of male infertility: An analysis of the evidence to support the development of global WHO guidance—challenges and future research opportunities. Human Reproduction Update, 23, 660–680. https://doi.org/10.1093/humupd/dmx021.
    7. Bayatli, F., Akkuş, D., Kiliç, E., Saraymen, R., & Sönmez, M. F. (2013). The protective effects of grape seed extract on MDA, AOPP, apoptosis and eNOS expression in testicular torsion: An experimental study. World Journal of Urology, 31, 615–622.
    8. Behdarvand-Margha, Z., & Ahangarpour, A. (2021). The effects of gallic acid and metformin on male reproductive dysfunction in diabetic mice induced by methylglyoxal: An experimental study. Iranian Journal of Reproductive Medicine, 19, 715–724. https://doi.org/10.18502/ijrm.v19i8.9619.
    9. Besong, E. B., & Ateufack, G. (2018). Leaf-methanolic extract of Pseudopanax arboreus (Araliaceae) (L. F. Phillipson) reverses amitriptyline-induced sexual dysfunction in male rats. Evidence-Based Complementary and Alternative Medicine, 2018, 2869727.
    10. Boeri, L., et al. (2021). Testicular volume in infertile versus fertile white-European men: A case-control investigation in the real-life setting. Asian Journal of Andrology, 23, 501–509. https://doi.org/10.4103/aja.aja_93_20.
    11. Boudou, F., Abdelkrim, B., Bendahmane, M., Baderdine, K., Adli, D., & Tou, N. (2013). Ameliorative effects of Syzygium aromaticum essential oil on fertility in male rats exposed to manganese. Advances in Sexual Medicine, 3, 85–91. https://doi.org/10.4236/asm.2013.34013.
    12. Bui-Le, T. N., & Hoang-Tan, Q. (2023). Protective effect of Curculigo orchioides Gaertn. extract on heat stress-induced spermatogenesis complications in murine model. Journal of Ethnopharmacology, 45, 3255–3267. https://doi.org/10.3390/cimb45040212.
    13. Bustani, G., Kareem, M., Al-Baghdady, H. A., & Al-Dhalimy, A. (2022). Protective effects of curcumin on testicular and sperm parameters abnormalities induced by nicotine in male rats. Andrologia. https://doi.org/10.1063/5.0066855.
    14. Cele, N. D., Sangweni, N. F., & Mosa, R. A. (2017). Testicular dysfunction ameliorative effect of the methanolic roots extracts of Maytenus procumbens and Ozoroa paniculosa. Evidence-Based Complementary and Alternative Medicine, 2017, 8204816.
    15. Cunha, G. R., Sinclair, A., Ricke, W. A., Robboy, S. J., Cao, M., & Baskin, L. S. (2019). Reproductive tract biology: Of mice and men. Differentiation, 110, 49–63. https://doi.org/10.1016/j.diff.2019.07.004.
    16. Ding, G. L., Liu, Y., Liu, M. E., Pan, J. X., Guo, M. X., Sheng, J. Z., & Huang, H. F. (2015). The effects of diabetes on male fertility and epigenetic regulation during spermatogenesis. Asian Journal of Andrology, 17, 948–953. https://doi.org/10.4103/1008-682X.150844.
    17. Eisenberg, M. L., & Esteves, S. C. (2023). Male infertility. Nature Reviews Disease Primers, 9, 49.
    18. El-Ashmawy, I. M., Saleh, A., & Salama, O. M. (2007). Effects of marjoram volatile oil and grape seed extract on ethanol toxicity in male rats. Basic & Clinical Pharmacology & Toxicology, 101, 320–327.
    19. Fungfuang, W., Lert-Amornpat, T., & Maketon, C. (2016). Effects of Black ginger (Kaempferia parviflora) on the testicular function in streptozotocin-induced diabetic male rats. Veterinary Integrative Sciences, 14(3), 95–107. retrieved from https://he02.tci-thaijo.org/index.php/vis/article/view/146103
    20. Hady, A., et al. (2023). Protective effects of curcumin and selenium on testicular toxicity induced by lead acetate in adult male albino rats [Structural and biochemical study]. International Journal of Medical Arts, 5, 3045–3053. https://doi.org/10.21608/ijma.2023.203141.1659.
    21. Hala, A., Khattab, I. Z., Abdallah, G. M., Kamel, K. H., & Kamel, M. (2010). Grape seed extract alleviate reproductive toxicity caused by aluminium chloride in male rats. Journal of American Science, 6.
    22. Hoang-Thi, A. P., Dang-Thi, A. T., Phan-Van, S., Nguyen-Ba, T., Truong-Thi, P. L., Le-Minh, T., Nguyen-Vu, Q. H., & Nguyen-Thanh, T. (2022). The impact of high ambient temperature on human sperm parameters: A meta-analysis. Iranian Journal of Public Health, 51, 710–723.
    23. Hou, Y., Yuan, P., Fu, Y., Zhang, Q., Wei, Y., Gao, L., Liu, L., Wang, X., & Zheng, X. (2020). Duzhong Butiansu prescription improves heat stress-induced spermatogenic dysfunction by regulating sperm formation and heat stress pathway. 2020, 6723204.
    24. Hozayen, W. (2013). The chemopreventive effects of ginger aqueous and methanolic extracts against alcohol-induced sexual dysfunction in rats. Medical Research Journal, 12, 108–114. https://doi.org/10.1097/01.MJX.0000437954.88749.53.
    25. Huang, B., Wang, Z., Kong, Y., Jin, M., & Ma, L. (2023). Global, regional and national burden of male infertility in 204 countries and territories between 1990 and 2019: An analysis of global burden of disease study. BMC Public Health, 23, 2195.
    26. Huang, H., Zhou, G., Liu, H., & Zhou, Z. (2017). Effect of total terpenes of Cornus officinalis Sieb. on hypogonadism in streptozotocin (STZ)-induced diabetic rats. International Journal of Clinical and Experimental Medicine, 10, 6926–6933.
    27. Hwang, D. S., Kim, H. G., Park, S., Hong, N. D., Ryu, J. H., & Oh, M. S. (2015). Effect of a traditional herbal prescription, Kyung-Ok-Ko, on male mouse spermatogenic ability after heat-induced damage. Evidence-Based Complementary and Alternative Medicine, 2015, 950829.
    28. Jang, M., Min, J. W., In, J. G., & Yang, D. C. (2011). Effects of red ginseng extract on the epididymal sperm motility of mice exposed to ethanol. International Journal of Toxicology, 30, 435–442. https://doi.org/10.1177/1091581811405074.
    29. Ji, H. J., Wang, D. M., Wu, Y. P., Niu, Y. Y., Jia, L. L., Liu, B. W., Feng, Q. J., & Feng, M. L. (2016). Wuzi Yanzong pill, a Chinese polyherbal formula, alleviates testicular damage in mice induced by ionizing radiation. BMC Complementary and Alternative Medicine, 16, 509.
    30. Karimi, S., Khorsandi, L., & Nejaddehbashi, F. (2019). Protective effects of curcumin on testicular toxicity induced by titanium dioxide nanoparticles in mice. JBRA Assisted Reproduction, 23, 344–351.
    31. Kim, M. K., Cha, K. M., Hwang, S. Y., Park, U. K., Seo, S. K., Lee, S. H., Jeong, M. S., Cho, S., Kopalli, S. R., & Kim, S. K. (2017). Pectinase-treated Panax ginseng protects heat stress-induced testicular damage in rats. Reproduction, 153, 737–747.
    32. Kim, Y. H., Kim, G. H., Shin, J. H., Kim, K. S., & Lim, J. S. (2010). Effect of Korean red ginseng on testicular tissue injury after torsion and detorsion. Korean Journal of Urology, 51, 794–799.
    33. Kopalli, S. R., Cha, K. M., Hwang, S. Y., Jeong, M. S., & Kim, S. K. (2019). Korean red ginseng (Panax ginseng Meyer) with enriched Rg3 ameliorates chronic intermittent heat stress-induced testicular damage in rats via multifunctional approach. Journal of Ginseng Research, 43, 135–142. https://doi.org/10.1016/j.jgr.2018.06.004.
    34. Kumar Roy, V., Marak, T. R., & Gurusubramanian, G. (2016). Alleviating effect of Mallotus roxburghianus in heat-induced testicular dysfunction in Wistar rats. Pharmaceutical Biology, 54, 905–918.
    35. Lamondo, D., Soegianto, A., Abadi, A., & Keman, S. (2014). Antioxidant effects of Sarang Semut (Myrmecodia pendans) on the apoptosis of spermatogenic cells of rats exposed to plumbum. Research Journal of Pharmaceutical, Biological and Chemical Sciences, 5.
    36. Lin, C., Shin, D. G., Park, S. G., Chu, S. B., Gwon, L. W., Lee, J. G., Yon, J. M., Baek, I. J., & Nam, S. Y. (2015). Curcumin dose-dependently improves spermatogenic disorders induced by scrotal heat stress in mice. Food & Function, 6, 3770–3777.
    37. López-Botella, A., & Velasco, I. (2021). Impact of heavy metals on human male fertility—An overview. Toxics, 10(7), 321. https://doi.org/10.1177/10.3390/antiox10091473.
    38. Mallick, C., Mandal, S., Barik, B., Bhattacharya, A., & Ghosh, D. (2007). Protection of testicular dysfunctions by MTEC, a formulated herbal drug, in streptozotocin-induced diabetic rat. Biological & Pharmaceutical Bulletin, 30, 84–90. https://doi.org/10.1248/bpb.30.84.
    39. Mohajeri, D., & Kaffashi Elahi, R. (2015). Effects of Nigella sativa on heat-induced testis damage in mouse. Bratislavské Lekárske Listy, 116, 264–269. https://doi.org/10.4149/bll_2015_051.
    40. Mt, M., Sk, M., T, Z., S, A., Ka, M., M, A., & Rj, H. (2018). The effect of alcoholic extract of ginger on apoptosis and inflammation of germ cells in streptozotocin-induced diabetic rats. Asian Journal of Biomedical and Pharmaceutical Sciences, 8, 1–7.
    41. Nguyen-Thanh, T., Dang-Ngoc, P., Bui, M.-H., Le-Minh, T., & Nguyen-Vu, Q.-H. (2024). Effectiveness of herbal medicines on male reproductive system: Evidence from meta-analysis. Pharmacological Research - Modern Chinese Medicine, 12, 100462. https://doi.org/10.1016/j.prmcm.2024.100462.
    42. Nouri, M., Khaki, A., Azar, F., & Rashidi, M.-R. (2009). The protective effects of carrot seed extract on spermatogenesis and cauda epididymal sperm reserves in gentamicin-treated rats. Yakhteh Medical Journal, 11, 327–334.
    43. Offor, S. J., Mbagwu, H. O., & Orisakwe, O. E. (2019). Improvement of lead acetate-induced testicular injury and sperm quality deterioration by Solanum anomalum Thonn. ex. Schumach fruit extracts in albino rats. Journal of Family & Reproductive Health, 13, 98–108.
    44. Panpan, Z., Alifu, N., Sataer, M., Yiming, A., Amuti, S., Wenjing, M., & Binghua, W. (2023). Effects of phytoestrogens combined with cold stress on sperm parameters and testicular proteomics in rats. Open Life Sciences, 18, 20220531.
    45. Park, H. J., & Koo, Y. K. (2017). Restoration of spermatogenesis using a new combined herbal formula of Epimedium koreanum Nakai and Angelica gigas Nakai in an luteinizing hormone-releasing hormone agonist-induced rat model of male infertility. Journal of Ginseng Research, 35, 170–177.
    46. Park, J. S., Hwang, S. Y., Lee, W. S., Yu, K. W., Paek, K. Y., Hwang, B. Y., & Han, K. (2006). The therapeutic effect of tissue cultured root of wild Panax ginseng C.A. Mayer on spermatogenetic disorder. Archives of Pharmacal Research, 29, 800–807.
    47. Pomjunya, A., Ratthanophart, J., & Fungfuang, W. (2017). Effects of Vernonia cinerea on reproductive performance in streptozotocin-induced diabetic rats. Journal of Veterinary Medical Science, 79, 572–578. https://doi.org/10.1292/jvms.16-0466.
    48. Sengupta, P., Borges, E., Jr., Dutta, S., & Krajewska-Kulak, E. (2018). Decline in sperm count in European men during the past 50 years. Human & Experimental Toxicology, 37, 247–255. https://doi.org/10.1177/0960327117703690.
    49. Shahraki, M., Dehvari, J., Shahrakipoor, M., Shahreki, E., Sharaki, A., & Dashipour, A. (2019). The effects of Anacyclus pyrethrum alcoholic root extract on FSH, LH, testosterone and sperm count in diabetic male rats. Zahedan Journal of Research in Medical Sciences, In Press. https://doi.org/10.5812/zjrms.88515.
    50. Sharma, V., Chauhan, N., Patil, U., & Dixit, V. (2021). Protective effect of rasayana herbs on lead acetate-induced testicular toxicity in Wistar rats. Indian Journal of Natural Products, 35, 9–15.
    51. Shi, G. J., Zheng, J., Wu, J., Qiao, H. Q., Chang, Q., Niu, Y., Sun, T., Li, Y. X., & Yu, J. Q. (2017). Protective effects of Lycium barbarum polysaccharide on male sexual dysfunction and fertility impairments by activating hypothalamic-pituitary-gonadal axis in streptozotocin-induced type-1 diabetic male mice. Endocrine Journal, 64, 907–922. https://doi.org/10.1507/endocrj.EJ16-0430.
    52. Sudjarwo, S. A., Sudjarwo, G. W., & Koerniasari. (2017). Protective effect of curcumin on lead acetate-induced testicular toxicity in Wistar rats. Research in Pharmaceutical Sciences, 12, 381–390. https://doi.org/10.4103/1735-5362.213983.
    53. Udefa, A. L., Amama, E. A., Archibong, E. A., Nwangwa, J. N., Adama, S., Inyang, V. U., Inyaka, G. U., Aju, G. J., Okpa, S., & Inah, I. O. (2020). Antioxidant, anti-inflammatory and anti-apoptotic effects of hydro-ethanolic extract of Cyperus esculentus L. (tigernut) on lead acetate-induced testicular dysfunction in Wistar rats. Biomedicine & Pharmacotherapy, 129, 110491. https://doi.org/10.1016/j.biopha.2020.110491.
    54. Wal, A., Wal, P., Pandey, A., Vig, H., Karunakaran, R., & Dash, B. (2022). Conventional treatment options and herbal remedies for male infertility: An overview. Asian Pacific Journal of Reproduction, 11, 1–6. https://doi.org/10.4103/2305-0500.350150.
    55. Yang, W.-S., Kim, I., Seu, Y.-B., Jeong, Y., Han, H., Ryu, K., & Kang, S. (2016). Ethanolic extract of radish sprout (Raphanus sativus L.) prevents bisphenol A-induced testicular dysfunction in male rats. Journal of Food Biochemistry, 40, e12307. https://doi.org/10.1111/jfbc.12245.
    56. Yuan, D., Wang, H., He, H., Jia, L., He, Y., Wang, T., Zeng, X., Li, Y., Li, S., & Zhang, C. (2014). Protective effects of total flavonoids from Epimedium on the male mouse reproductive system against cyclophosphamide-induced oxidative injury by up-regulating the expressions of SOD3 and GPX1. Phytotherapy Research, 28, 88–97. https://doi.org/10.1002/ptr.4956.
    57. Zhang, K., et al. (2020). Effects of Qilin pills on spermatogenesis, reproductive hormones, oxidative stress, and the TSSK2 gene in a rat model of oligoasthenospermia. Andrologia, 20, 42.
    58. Zirkin, B. R., Santulli, R., Awoniyi, C. A., & Ewing, L. L. (1989). Maintenance of advanced spermatogenic cells in the adult rat testis: Quantitative relationship to testosterone concentration within the testis. Endocrinology, 124, 3043–3049. https://doi.org/10.1210/endo-124-6-304

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Copyright (c) 2025 The Authors

How to cite

Dang-Ngoc, P., Bui, M.-H., & Nguyen-Thanh, T. (2025). Protective effect of herbal medicine on murine spermatogenesis under heat stress and other injury models: Evidence from meta-analyses. Journal of Animal Behaviour and Biometeorology, 13(1), 2025007. https://doi.org/10.31893/jabb.2025007
  • Article viewed - 1233
  • PDF downloaded - 139