Phytotherapy for Bacterial Vaginosis with Piper Betle: from Mechanism to Safety

Authors

  • Satria Bintang Samudra Faculty of Medicine, Hang Tuah University
  • Prawesty Diah Utami FK University Hang Tuah
  • Grissabel Bethrin Jiantoro Faculty of Medicine, Hang Tuah University
  • Jessica Euodia Adidharma Faculty of Medicine, Hang Tuah University
  • Rayhan Ali Fadli Faculty of Medicine, Hang Tuah University

DOI:

https://doi.org/10.22225/ijbstm.3.1.2026.7-16

Keywords:

antimicrobial effect, bacterial vaginosis, phenolic constituent, Piper betle

Abstract

Background: Bacterial vaginosis (BV) is a prevalent vaginal dysbiosis characterized by depletion of Lactobacillus and overgrowth of anaerobic bacteria, commonly including Gardnerella vaginalis. Clinical management is complicated by high recurrence rates, which are closely linked to polymicrobial biofilm persistence and the limited microbiome selectivity of conventional antimicrobials. This narrative review aimed to synthesize current evidence on the phytotherapeutic potential of Piper betle in BV, focusing on antimicrobial and anti-biofilm mechanisms, modulation of vaginal microbiome ecology, and safety and standardization considerations relevant to translational development and recurrence prevention. Methods: An exploratory literature search (2015–2025) was conducted using PubMed/MEDLINE, ScienceDirect, and Google Scholar, complemented by manual reference screening, and last searched on 30 September 2025. Results: Findings across in vitro studies, observational reports, and mechanistic literature indicate that P. betle extracts and key phenolic constituents, particularly hydroxychavicol and eugenol, exhibit antibacterial activity against BV-associated taxa and anti-virulence effects consistent with biofilm weakening and interference with quorum-sensing–regulated behaviors. Importantly, several studies suggest comparatively limited inhibitory effects on Lactobacillus spp., supporting the plausibility of a microbiome-sparing profile that may facilitate restoration of vaginal eubiosis. Nevertheless, the evidence base is constrained by heterogeneous methodologies, predominance of preclinical models, and substantial variability in phytochemical composition across preparations. Conclusion: Overall, P. betle emerges as a biologically plausible adjunctive or preventive candidate for preventing BV recurrence, warranting standardized formulations, marker-based quality control, and rigorous clinical evaluation with recurrence-focused endpoints.

References

1. Abbe, C., and Mitchell, C. M. (2023). Bacterial vaginosis: A review of approaches to treatment and prevention. Frontiers in Reproductive Health, 5, 1–13. https://doi.org/10.3389/frph.2023.1100029

2. Basheer, A. (2022). The art and science of writing narrative reviews. International Journal of Advanced Medical and Health Research, 9(2), 124–126.

3. Biswas, P., Anand, U., Saha, S. C., Kant, N., Mishra, T., Masih, H., Bar, A., Pandey, D. K., Jha, N. K., Majumder, M., Das, N., Gadekar, V. S., Shekhawat, M. S., Kumar, M., Radha, Pro?ków, J., Lastra, J. M. P., and Dey, A. (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. https://doi.org/10.1111/jcmm.17323

4. Bradshaw, C. S., and Brotman, R. M. (2015). Making inroads into improving treatment of bacterial vaginosis: Striving for long-term cure. BMC Infectious Diseases, 15(1), 1–12. https://doi.org/10.1186/s12879-015-1027-4

5. Carolin, B. T., et al. (2024). Effect of boiled betel leaf and turmeric on pathological vaginal discharge. International Journal of Midwifery and Health Sciences, 2(3), 49–58.

6. Dubé-Zinatelli, E., Cappelletti, L., and Ismail, N. (2025). The vaginal microbiome in bacterial vaginosis: Pathogenesis, reproductive impacts, and emerging therapies. Journal of Reproductive Immunology, 172, 104804. https://doi.org/10.1016/j.jri.2025.104804

7. Gao, M., Manos, J., Whiteley, G., and Zablotska-Manos, I. (2024). Antibiofilm agents for the treatment and prevention of bacterial vaginosis: A systematic narrative review. The Journal of Infectious Diseases, 230(3), e508–e517. https://doi.org/10.1093/infdis/jiae134

8. Jalil, V., Khan, M., Haider, S. Z., and Shamim, S. (2022). Investigation of the antibacterial, anti-biofilm, and antioxidative effect of Piper betle leaf extract against Bacillus gaemokensis MW067143 isolated from dental caries: An in vitro-in silico approach. Microorganisms, 10(12), 2485. https://doi.org/10.3390/microorganisms10122485

9. Jantorn, P., Tipmanee, V., Wanna, W., Prapasarakul, N., Visutthi, M., and Sotthibandhu, D. S. (2023). Potential natural antimicrobial and antibiofilm properties of Piper betle L. against Staphylococcus pseudintermedius and methicillin-resistant strains. Journal of Ethnopharmacology, 317, 116820. https://doi.org/10.1016/j.jep.2023.116820

10. Kim, E. S., Waltmann, A., Duncan, J. A., and Hood-Pishchany, I. (2025). Advances in treating bacterial vaginosis: Recognizing sexual transmission and pipeline of therapies. Current Opinion. Infectious Diseases, 39(1), 67–74 https://doi.org/10.1097/QCO.0000000000001172

11. Krzy?ek, P. (2019). Challenges and limitations of anti-quorum-sensing therapies. Frontiers in Microbiology, 10, 2473. ttps://doi.org/10.3389/fmicb.2019.02473

12. Kusuma, S. A. F., Tjitraresmi, A., and Susanti, G. (2017). Antibacterial effect of red Piper betel leaf (Piper crocatum Ruiz & Pav.) ethanol extracts on Lactobacillus acidophilus and L. bifidus growth inhibition. Asian Journal of Pharmaceutical and Clinical Research, 10(14), 65. https://doi.org/10.22159/ajpcr.2017.v10s2.19490

13. Lachyan, A., Khunger, N., and Panda, P. S. (2024). Bacterial vaginosis and biofilms: Therapeutic challenges and innovations—A narrative review. Indian Journal of Dermatology, Venereology and Leprology, 90(6), 750–754. https://doi.org/10.25259/IJDVL_1322_2023

14. Lade, H., Paul, D., and Kweon, J. H. (2014). Quorum-quenching-mediated approaches for control of membrane biofouling. International Journal of Biological Sciences, 10(5), 550–565. https://doi.org/10.7150/ijbs.9028

15. Lao, R. C. C., Yabes, A. M., Tobias-Altura, M., Panganiban, L. C. R., and Makalinao, I. R. (2023). In vitro antibacterial and antibiofilm activities of Piper betle L. ethanolic leaf extract on Staphylococcus aureus ATCC 29213. Acta Medica Philippina, 57(12), 53–60. https://doi.org/10.47895/amp.vi0.6412

16. Leesombun, A., Sungpradit, S., Bangphoomi, N., Thongjuy, O., Wechusdorn, J., Riengvirodkij, S., Wannawong, J., and Boonmasawai, S. (2023). Effects of Piper betle extracts against biofilm formation by methicillin-resistant Staphylococcus pseudintermedius isolated from dogs. Pharmaceuticals, 16(5), 741. https://doi.org/10.3390/ph16050741

17. Mudayatiningsih, S., and Suryandari, E. S. D. H. (2018). The difference of Lactobacillus vaginalis normal flora bacteria on vaginal swab on women at childbearing age using Piper betle L., soap, and water as vaginal cleanser. GSC Biological and Pharmaceutical Sciences, 5(3), 66–70. https://doi.org/10.30574/gscbps.2018.5.3.0143

18. Muzny, C. A., and Sobel, J. D. (2022). The role of antimicrobial resistance in refractory and recurrent bacterial vaginosis and current recommendations for treatment. Antibiotics, 11(4), 1–12. https://doi.org/10.3390/antibiotics11040500

19. Nayaka, N. M. D. M. W., Sasadara, M. M. V., Sanjaya, D. A., Yuda, P. E. S. K., Dewi, N. L. K. A. A., Cahyaningsih, E., and Hartati, R. (2021). Piper betle (L.): Recent review of antibacterial and antifungal properties, safety profiles, and commercial applications. Molecules, 26(8), 2321. https://doi.org/10.3390/molecules26082321

20. Núño, K., Jensen, A. S., O’Connor, G., Houston, T. J., Dikici, E., Zingg, J. M., Deo, S., and Daunert, S. (2024). Insights into women’s health: Exploring the vaginal microbiome, quorum sensing dynamics, and therapeutic potential of quorum sensing quenchers. Molecular Aspects of Medicine, 100, 101304. https://doi.org/10.1016/j.mam.2024.101304

21. Nuraini, D. F., Yanti, N. L. G. P., Parwati, P. A., and Prihatiningsih, D. (2025). The effect of giving green betel leaf extract on the growth of Bacteroides in vaginal secret culture. Multidisciplinary Indonesian Center Journal, 2(4), 4476–4482. https://doi.org/10.62567/micjo.v2i4.1277

22. Phensri, P., Thummasema, K., Sukatta, U., Morand, S., and Pruksakorn, C. (2022). In vitro antimicrobial activity of Piper betle leaf extract and some topical agents against methicillin-resistant and methicillin-susceptible Staphylococcus strains from canine pyoderma. Animals, 12(22), 1–13. https://doi.org/10.3390/ani12223203

23. Rahmi, and Firdausi, R. (2024). The effectiveness of Piper betle Linn decoction administration on Nn. U with pathological vaginal discharge. Journal of Health, 4(1), 39–42. https://banuainstitute.org/JOHE/article/view/127

24. Ratchasong, K., Saengsawang, P., Yusakul, G., Makkliang, F., Lakhanapuram, H. K., Wintachai, P., Thomrongsuwannakij, T., Nwabor, O. F., Punyapornwithaya, V., Romyasamit, C., and Mitsuwan, W. (2025). Bactericidal activities of nanoemulsion containing Piper betle L. leaf and hydroxychavicol against avian pathogenic Escherichia coli and modelling simulation of hydroxychavicol against bacterial cell division proteins. Antibiotics, 14(8), 788. https://doi.org/10.3390/antibiotics14080788

25. Sarma, C., Rasane, P., Kaur, S., Singh, J., Singh, J., Gat, Y., Garba, U., Kaur, D., and Dhawan, K. (2018). Antioxidant and antimicrobial potential of selected varieties of Piper betle L. (Betel leaf). Anais da Academia Brasileira de Ciências, 90(4), 3871–3878. https://doi.org/10.1590/0001-3765201820180285

26. Sikdar, B., Mukherjee, S., Bhattacharya, R., Raj, A., Roy, A., Banerjee, D., Gangopadhyay, G., and Roy, S. (2024). The anti-quorum-sensing and biofilm-inhibitory potential of Piper betle L. leaf extract and prediction of the roles of the potent phytocompounds. Microbial Pathogenesis, 195, 106864. https://doi.org/10.1016/j.micpath.2024.106864

27. Singh, D., Narayanamoorthy, S., Gamre, S., Majumdar, A. G., Goswami, M., Gami, U., Cherian, S., and Subramanian, M. (2018). Hydroxychavicol, a key ingredient of Piper betle, induces bacterial cell death by DNA damage and inhibition of cell division. Free Radical Biology and Medicine, 120, 62–71. https://doi.org/10.1016/j.freeradbiomed.2018.03.021

28. Sousa, L. G. V., Pereira, S. A., and Cerca, N. (2023). Fighting polymicrobial biofilms in bacterial vaginosis. Microbial Biotechnology, 16(7), 1423–1437. https://doi.org/10.1111/1751-7915.14261

29. Sukhera, J. (2022). Narrative reviews: Flexible, rigorous, and practical. Journal of Graduate Medical Education, 14(4), 414–417.

30. Vedu, A., Keren, H., P, P., Krishnan, S., Monica, S. J., and Perumal, A. (2025). Exploring the pharmacological potential of Pandanus tectorius floral extract: An investigation of its therapeutic activities and bioactive compounds. Asian Journal of Biological and Life Sciences, 13(3), 821–829. https://doi.org/10.5530/ajbls.2024.13.99

31. Watkins, E., Cimino, A. N., Culbertson, C., Raymaker, J., and Amico, J. R. (2025). Understanding patient perceptions of bacterial vaginosis treatments: A mixed-methods sentiment analysis of online drug review forums. Online Journal of Public Health Informatics, 17(1), e71720. https://doi.org/10.2196/71720

32. World Health Organization. (2025, November 21). Bacterial vaginosis. https://www.who.int/news-room/fact-sheets/detail/bacterial-vaginosis

Downloads

Published

2026-04-07

Issue

Section

Articles