Jiawei Ermiao Granules (JWEMGs) clear persistent HR-HPV infection though improving vaginal microecology

Ethnopharmacological relevance: Jiawei Ermiao Granules (JWEMGs), a traditional Chinese herbal formulation, has been widely used in China for the treatment of human papillomavirus (HPV) infections. However, the underlying mechanisms through which it exerts its Antiviral effects remain poorly understood.

Aim of the study: This study aimed to investigate the potential mechanisms by which JWEMGs modulate vaginal microecology and clear HPV infections, utilizing clinical trials, metagenomic Sequencing, and in vitro models.

Materials and methods: Clinical indicators related to vaginal microecology, such as vaginal pH, cleanliness, Nugent score, Donders score, catalase, neuraminidase, and leukocyte esterase, were evaluated in 65 patients with high-risk HPV (HR-HPV) Infection. The study examined the impact of two courses of oral JWEMGs on these clinical parameters. Additionally, metagenomic Sequencing was performed on vaginal lavage samples from 33 patients to assess the alteration of the vaginal microbiome following JWEMGs treatment. Immunohistochemistry was used to detect ALPK1 expression in cervical exfoliated cells, and ELISA was employed to measure cytokine levels in vaginal lavage fluid. JWEMGs intervention was applied to HaCaT-HPV E6/E7 cells to evaluate its effects on restoring α-kinase 1 (ALPK1) expression and promoting the secretion of cytokines and chemokines.

Results: Treatment with JWEMGs significantly improved several clinical indicators, including cleanliness, pH, Nugent score, Donders score, catalase, neuraminidase, and leukocyte esterase, in HR-HPV-infected patients. Furthermore, JWEMGs therapy led to an increased abundance of Lactobacillus species, especially Lactobacillus crispatus, and a marked reduction in Gardnerella species. JWEMGs treatment also significantly promoted ALPK1 expression in cervical exfoliated cells and augmented the secretion of key cytokines, including IL-6, IL-8, and TNF-α. In parallel, in vitro results showed that JWEMGs substantially enhanced IL-6, IL-8, TNF-α, CCL2, CCL5, and CCL7 secretion in HaCaT-HPV E6/E7 cells, which correlated with the activation of the ALPK1/NF-κB signaling pathway.

Conclusion: In conclusion, JWEMGs treatment effectively remodels the vaginal microbiota and bolsters mucosal immunity in the lower genital tract, thereby improving the vaginal microecology in HR-HPV-infected individuals. In vitro findings further demonstrated that JWEMGs promote cytokine and chemokine expression, activating the ALPK1/NF-κB pathway.

ALPK1/NF-κB pathway; HR-HPV infection; Jiawei Ermiao Granules; Mucosal immunity; Vaginal microecology.