Effect Of Kangfuxin Liquid On Vulvovaginal Candidiasis By Regulating Th17 Cells

Background:Under the influence of various pathogenic factors,vulvovaginal candidiasis（VVC）is an infectious disease of female external reproductive tract caused by ecological imbalance in the vagina^[1],which brings harm to women’s physical and mental health.However,the frequency of drug-resistant candida isolates is increasing due to the overuse of antifungal agents,non-standard treatment and the limitation of drugs,making clinical antifungal treatment difficult.There is an urgent need to find new drugs or treatments.Nowadays,a number of studies have shown that Traditional Chinese medicine preparation has a good prevention and treatment effect in vulvovaginal candidiasis,and it has become a new choice.Aim:The purpose of this study was to explore the effect and mechanism of Kangfuxin（KFX）solution in the treatment of vulvovaginal candidiasis in mice.Methods:The antifungal activity of KFX solution against different Candida albicans（C.albicans）was determined by microdilution method.The effects of KFX solution on the growth and development of C.albicans mycelia were evaluated by different liquid mycelia-inducing media.Morphological changes of C.albicans were observed by scanning electron microscopy.q PCR was used to detect mycelia-related gene expression levels.Label-free proteomics was used to analyze C.albicans treated with KFX solution.A mouse model of vulvovaginal candidiasis of drug-resistant C.albicans was established,and the changes of body weight,vaginal symptoms and colony count were observed after treatment with KFX.The adhesion and colonization of C.albicans in vagina of mice were observed by silver hexamine periodate staining（PASM）.Hematoxylin-eosin staining（HE）was used to analyze the infiltration of vaginal inflammatory.The changes of inflammatory cytokines in vaginal endocrine of mice after KFX solution treatment were determined by enzymoly-linked immunosorbent assay（ELISA）.The expression of STAT3 in vagina of mice was determined by immunofluorescence.Results:KFX solution had good inhibitory effect on both standard and clinical strains of C.albicans,and its minimum inhibitory concentration(MIC₅₀)of C.albicans was 20%-38%.KFX solution could inhibit the growth of C.albicans mycelia in different liquid mycelia-inducing media,and it was most obvious at 8 h.After KFX solution treated C.albicans,the expression of mycely-related genes CPH1,TEC1,HWP1 and UME6 decreased,while the expression of TUP1 increased.Proteomics indicated that KFX may affect energy metabolism,signal transduction and translation of C.albicans.Especially,steroid biosynthesis is most obvious in mycelium,biofilm,drug resistance,immune regulation,energy metabolism and other aspects.At the same time,KFX solution also showed good activity in vivo,restored the body weight of VVC mice,reduced vulvovaginal symptoms,and reduced the adhesion and colonization of C.albicans.The secretion of Interleukin-17A（IL-17A）,IL-6,Interferon-γ（IFN-γ）and STAT3 increased significantly in VVC mice,while the secretion of Tumor necrosis factor-α（TNF-α）decreased.Conclusion:KFX solution has a significant therapeutic effect on vaginal candidiasis.KFX can inhibit the growth and development of C.albicans mycelia,increase IFN-γsecretion,and regulate IL-6 activation of STAT3 pathway to promote the release of IL-17 A in the treatment of vulvovaginal candidiasis.This study provides basic data for the application of KFX as a clinical antifungal agent and provides a new strategy for the treatment of vaginal candidiasis.