Main Article Content


Background: Currently, there are still very limited male contraceptive options. The ideal male contraceptive is still needed and ideally has the characteristics of having sufficient effectiveness,  fully reversible and safe for long-term use.  Several studies have been conducted to explore Piper betle as a contraceptive. Objectives: This study aims to examine the effect of 96% ethanol extract of sirih leaf (Piper betle L.) in reducing rat spermatogenesis quality, which includes the number, concentration, motility and morphology of male rat sperm. Material and Methods: This study used a posttest design with 28 white male rats. The rats were divided into four groups, each consisting of 7 rats. Group I was a control group. The test groups were group II, III, IV, and V, and each received an ethanolic extract of Piper betle leaves with various dosages of 200, 400, and 800 mg/kg body weight (BW), respectively, for 30 days. On day 31, all mice were sacrificed and analyzed for sperm count and concentration, sperm motility and sperm morphology. Results: The administration of 96% Piper betle leaves ethanol extract (PBEE) decreased the number and concentration of rats sperm, decreased progressive sperm motility and reduced the proportion of normal morphological rat sperm. PBEE at 800 mg/kg BW dose showed the greatest decreasing effect among all doses (p = 0.01). Conclusions: PBEE has contraceptive ability with a mechanism to reduce sperm count and concentration, sperm motility and sperm morphology.


Sirih leaf (Piper betle L.) Contraception Antifertility Sperm concentration Sperm motility Sperm morphology

Article Details

How to Cite
Lubis, M., & Syahfitri, W. (2023). Antifertility Effect of Sirih Leaf (Piper betle L.) Ethanol Extract on Male Wistar Rats Spermatogenesis: Efek Antifertilitas Ekstrak Etanol Daun Sirih (Piper betle L.) Pada Spermatogenesis Tikus Wistar Jantan. Jurnal Farmasi Galenika (Galenika Journal of Pharmacy) (e-Journal), 9(1), 110-118.


  1. Badan Kependudukan dan Keluarga Berencana Nasional. (2020). Rencana strategis Badan Kependudukan dan Keluarga Berencana Nasional (2020-2024). Jakarta: Badan Kependudukan dan Keluarga Berencana Nasional.
  2. Barclay, K. J., & Kolk, M. (2018). Birth Intervals and Health in Adulthood: A Comparison of Siblings Using Swedish Register Data. Demography, 55(3), 929–955. doi:10.1007/s13524-018-0673-8
  3. Biswas, P., Anand, U., Saha, S. C., Kant, N., Mishra, T., Masih, H., (2022). Betelvine (Piper betle L.): A comprehensive insight into its ethnopharmacology, phytochemistry, and pharmacological, biomedical and therapeutic attributes. Journal of Cellular and Molecular Medicine, 26(11), 3083–3119. doi:10.1111/jcmm.17323
  4. Chakraborty, J. B., Mahato, S. K., Joshi, K., Shinde, V., Rakshit, S., Biswas, N., et. al. (2012). Hydroxychavicol, a Piper betle leaf component, induces apoptosis of CML cells through mitochondrial reactive oxygen species-dependent JNK and endothelial nitric oxide synthase activation and overrides imatinib resistance. Cancer Science, 103(1), 88–99. doi:10.1111/j.1349-7006.2011.02107.x
  5. Chang, M. C., Uang, B. J., Tsai, C. Y., Wu, H. L., Lin, B. R., Lee, C. S., et. al. (2007). Hydroxychavicol, a novel betel leaf component, inhibits platelet aggregation by suppression of cyclooxygenase, thromboxane production and calcium mobilization: Antiplatelet effect of hydroxychavicol. British Journal of Pharmacology, 152(1), 73–82. doi:10.1038/sj.bjp.0707367
  6. Chang, M. C., Uang, B. J., Wu, H. L., Lee, J. J., Hahn, L. J., & Jeng, J. H. (2002). Inducing the cell cycle arrest and apoptosis of oral KB carcinoma cells by hydroxychavicol: roles of glutathione and reactive oxygen species: Hydroxychavicol as antioxidant and prooxidant. British Journal of Pharmacology, 135(3), 619–630. doi:10.1038/sj.bjp.0704492
  7. Chao, J., Page, S. T., & Anderson, R. A. (2014). Male contraception. Best Practice and Research: Clinical Obstetrics and Gynaecology, 28(6), 845–857. doi:10.1016/j.bpobgyn.2014.05.008
  8. Gundala, S. R., & Aneja, R. (2014). Piper betel leaf: A reservoir of potential xenohormetic nutraceuticals with cancer-fighting properties. Cancer Prevention Research, 7(5), 477–486. doi:10.1158/1940-6207.CAPR-13-0355
  9. Naik, A., & Changamma, C. (2015). Enzymatic Studies with Reference to Antifertility Potential of Piper betle Linn. Leaf Stalk Extract in Male Albino Rats. Annual Research & Review in Biology, 5(3), 246–253. doi:10.9734/ARRB/2015/11560
  10. Neisi, N., Noorbakhsh, R., Hashemitabar, M., Afroogh, M., & Cheraghian, B. (2022). Hepatitis B Virus and Cytomegalovirus Infections Disrupt Sperm Parameters in Males through Decreasing Mitochondrial Membrane Potential: A Case-control Study. Jundishapur Journal of Microbiology, 15(7). doi:10.5812/jjm-128539
  11. Paranjpe, R., Gundala, S. R., Lakshminarayana, N., Sagwal, A., Asif, G., Pandey, A., & Aneja, R. (2013). Piper betel leaf extract: anticancer benefits and bio-guided fractionation to identify active principles for prostate cancer management. Carcinogenesis, 34(7), 1558–1566. doi:10.1093/carcin/bgt066
  12. Ratnasooriya, W. D., & Premakumara, G. A. S. (1997). Piper betle leaves reversibly inhibits fertility of male rats. Vidyodaya J. of Sci, 7, 15–21.
  13. Sarkar, M., Gangopadhyay, P., Basak, B., Chakrabarty, K., Banerji, J., Adhikary, P., et. al. (2001). The reversible antifertility effect of Piper betle Linn. on Swiss albino male mice. Contraception, 62, 271–274.
  14. Shah, S. K., & Jhade, D.N. (2016). Antifertility activity of ethanolic and aqueous extracts of Piper betle petiole on female Wistar rats. International Journal of Green Pharmacy, 10(4), 204–210.
  15. Singh, A., Kala, S., Kapoor, D.N., Gupta, R., Virk, A., Singh, S., et. al. (2011). Effect on human sperm mitochondrial activity by Piper betle and Calendula officinalis. Scholars Research Library Annals of Biological Research, 2(5), 622–627.
  16. Wuwungan, C., Queljoe, E., & Wewengkang, D.S. (2017). Kualitas spermatozoa tikus putih jantan galur wistar (Rattus norvegicus L.) setelah pemberian ekstrak etanol daun sirih (Piper Betle L). Pharmacon Jurnal Ilmiah Farmasi, 6(3), 324–331.