Berberine promising therapy to treat vulvovaginal candidiasis

“Although some antifungal drugs such as azoles have been applied clinically for many years, their therapeutic value is very limited due to the emergence of drug-resistant strains,” wrote the authors.¹

Previous studies have shown that the adhesion of Candida albicans (C. albicans) to vaginal epithelial cells is essential for the pathogenesis of vulvovaginal candidiasis (VVC).²

Thus, preventing the adhesion of C. albicans to vaginal epithelial cells might be an effective strategy to treat VVC.

Berberine, a quaternary ammonium compound, is the most prevalent bioactive component found in two traditional Chinese herbs: Coptis chinensis Franch (Ranunculaceae) and Phellodendron chinense C.K.Schneid (Rutaceae).

Applied clinically, berberine treats diseases like bacterial diarrhea and diabetes, plus can function as an antibacterial, antifungal, anti-inflammatory, immunomodulatory, and even as an anti-cancer agent.

The antifungal mechanism of berberine may entail the down-regulation of some key genes related to the integrity of the C. albicans cell wall after treatment with this compound, such as the hypha-specific gene ECE1 related to the morphological transformation of C. albicans and the genes FKS1 and FKS2 linked to the synthesis of beta-glucan components of C. albicans.

For the study, C. albicans SC5314 was provided by the College of Pharmacy, Second Military Medical University in Shanghai, China. The glycerol-preserved fungal strain removed from the -80° C refrigerator was initially streaked onto Sabouraud’s agar.

Then, by using a single colony, the strain was routinely inoculated for three generations in Sabouraud’s agar plates. Afterward, the strain was activated and propagated in liquid Sabouraud medium at 37° C for 12 to 16 hours, until exponential growth phase was achieved.

Revived C. albicans cells were pooled by centrifugation at 3,000 ×g. After two washing steps with sterile phosphate buffered saline (PBS), cells were resuspended in RPMI-1640 medium and adjusted to a defined cell density via a hemocytometer, prior to subsequent tests.

For cell culture, A431 human vaginal epidermoid carcinoma cell line was cultured at 37°C with 5% CO2 in Dulbecco’s Modified Eagle’s Medium, supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin.

At 24 hours prior to experimentation, the culture medium was replaced with serum-free medium and maintained until cell harvest.

Gram staining was used to observe the adherence of C. albicans.

This study demonstrated that berberine significantly inhibited the adhesion of C. albicans to vaginal epithelial cells by reducing the expressions of intercellular adhesion molecule 1 (ICAM-1) and the proteins mucin 1 and mucin 4 in vaginal epithelial cells, which are vital in modulating the adhesion of C. albicans to host cells, according to the authors.

Berberine also balanced interleukin-2 (IL-2) and interleukin-4 (IL-4) expressions, which are instrumental in regulating the inflammatory response caused by C. albicans infection.

“Hence, our findings demonstrate that berberine may be a potential therapeutic agent for VVC by interfering with the adhesion of C. albicans to vaginal epithelial cells and represents a new pathway for developing antifungal therapies agents from natural herbs,” wrote the authors.

References

1. Zhao T, Zhang K, Shi G, et al. Berberine inhibits the adhesion of Candida albicans to vaginal epithelial cells. Front Pharmacol. Published online February 28, 2022. doi:10.3389/fphar.2022.814883

2. Martin H., Govern MM, Abbey L. et al. Inhibition of adherence of the yeast Candida albicans to buccal epithelial cells by synthetic aromatic glycoconjugates. Eur J. Med Chem. 2018;160, 82–93.