Kangbainian Lotion Ameliorates Vulvovaginal Candidiasis in Mice by Inhibiting the Growth of Fluconazole-Resistant and the Dectin-1 Signaling Pathway Activation

Overview

Journal Front Pharmacol

Date 2022 Feb 10

PMID 35140608

Authors

Zewei Chen

Tengshuo Luo

Fengke Huang

Fuzhen Yang

Wenting Luo

Guanfeng Chen

Mengfei Cao

Fengyun Wang

Jun Zhang

Affiliations

Soon will be listed here.

Abstract

Vulvovaginal candidiasis (VVC) is an infectious disease caused by species, which affects millions of women worldwide every year. The resistance to available antifungal drugs for clinical treatment is a growing problem. The treatment of refractory VVC caused by azole-resistant is still facing challenges. However, research on new antifungal drugs is progressing slowly. Although a lot of reports on new antifungal drugs, only three new antifungal drugs (Isavuconazole, ibrexafungerp, and rezafungin) and two new formulations of posaconazole were marketed over the last decade. Chinese botanical medicine has advantages in the treatment of drug-resistant VVC, such as outstanding curative effects and low adverse reactions, which can improve patients' comfort and adherence to therapy. Kangbainian lotion (KBN), a Chinese botanical formulation, has achieved very good clinical effects in the treatment of VVC. In this study, we investigated the antifungal and anti-inflammatory effects of KBN at different doses in fluconazole-resistant (FLC-resistant) VVC model mice. We further studied the antifungal mechanism of KBN against FLC-resistant () and the anti-inflammatory mechanism correlated with the Dectin-1 signaling pathway. and results showed that KBN had strong antifungal and anti-inflammatory effects in FLC-resistant VVC, such as inhibiting the growth of and vaginal inflammation. Further studies showed that KBN inhibited the biofilm and hypha formation, reduced adhesion, inhibited ergosterol synthesis and the expression of ergosterol synthesis-related genes , and reduced the expression of drug-resistant efflux pump genes and of FLC-resistant . In addition, results showed that KBN reduced the expression of inflammatory factor proteins TNF-α, IL-1β, and IL-6 in vaginal tissues, and inhibited the expression of proteins related to the Dectin-1 signaling pathway. In conclusion, our study revealed that KBN could ameliorate vaginal inflammation in VVC mice caused by FLC-resistance . This effect may be related to inhibiting the growth of FLC-resistance and Dectin-1 signaling pathway activation.

Citing Articles

and synergistic inhibition of targeting cell membranes by and extracts.

Li L, He Y, Zou Q, Chen W, Liu Y, He H Front Microbiol. 2024; 15:1456240.

PMID: 39323889 PMC: 11423746. DOI: 10.3389/fmicb.2024.1456240.

Synergistic activity and mechanism of KBN lotion and miconazole nitrate against drug-resistant biofilms.

Cao X, Xiao N, Huang J, Li L, Zhong L, Zhang J Front Cell Infect Microbiol. 2024; 14:1426791.

PMID: 39268490 PMC: 11390680. DOI: 10.3389/fcimb.2024.1426791.

Licochalcone A Protects Vaginal Epithelial Cells Against Candida albicans Infection Via the TLR4/NF-κB Signaling Pathway.

Li W, Yin Y, Li T, Wang Y, Shi W J Microbiol. 2024; 62(7):525-533.

PMID: 38819759 DOI: 10.1007/s12275-024-00134-z.

References

Tam J, Reedy J, Lukason D, Kuna S, Acharya M, Khan N . Tetraspanin CD82 Organizes Dectin-1 into Signaling Domains to Mediate Cellular Responses to . J Immunol. 2019; 202(11):3256-3266. PMC: 6529278. DOI: 10.4049/jimmunol.1801384. View

Fazly A, Jain C, Dehner A, Issi L, Lilly E, Ali A . Chemical screening identifies filastatin, a small molecule inhibitor of Candida albicans adhesion, morphogenesis, and pathogenesis. Proc Natl Acad Sci U S A. 2013; 110(33):13594-9. PMC: 3746938. DOI: 10.1073/pnas.1305982110. View

White T, Holleman S, Dy F, Mirels L, Stevens D . Resistance mechanisms in clinical isolates of Candida albicans. Antimicrob Agents Chemother. 2002; 46(6):1704-13. PMC: 127245. DOI: 10.1128/AAC.46.6.1704-1713.2002. View

Huysamen C, Brown G . The fungal pattern recognition receptor, Dectin-1, and the associated cluster of C-type lectin-like receptors. FEMS Microbiol Lett. 2008; 290(2):121-8. PMC: 2704933. DOI: 10.1111/j.1574-6968.2008.01418.x. View

Yang F, Ding S, Liu W, Liu J, Zhang W, Zhao Q . Antifungal activity of 40 TCMs used individually and in combination for treatment of superficial fungal infections. J Ethnopharmacol. 2015; 163:88-93. DOI: 10.1016/j.jep.2015.01.025. View

Dovnik A, Golle A, Novak D, Arko D, Takac I . Treatment of vulvovaginal candidiasis: a review of the literature. Acta Dermatovenerol Alp Pannonica Adriat. 2015; 24(1):5-7. DOI: 10.15570/actaapa.2015.2. View

Pfaller M, Diekema D, Sheehan D . Interpretive breakpoints for fluconazole and Candida revisited: a blueprint for the future of antifungal susceptibility testing. Clin Microbiol Rev. 2006; 19(2):435-47. PMC: 1471993. DOI: 10.1128/CMR.19.2.435-447.2006. View

Drummond R, Brown G . The role of Dectin-1 in the host defence against fungal infections. Curr Opin Microbiol. 2011; 14(4):392-9. DOI: 10.1016/j.mib.2011.07.001. View

Liu Q, Luyten W, Pellens K, Wang Y, Wang W, Thevissen K . Antifungal activity in plants from Chinese traditional and folk medicine. J Ethnopharmacol. 2012; 143(3):772-8. DOI: 10.1016/j.jep.2012.06.019. View

10.

Niu H, Duan Q, Shi G, Wu D, Shao J, Wang T . [Inhibitory effect of extract of Coptidis Rhizoma on invasion of Candida albicans hyphae in vitro]. Zhongguo Zhong Yao Za Zhi. 2019; 44(1):125-130. DOI: 10.19540/j.cnki.cjcmm.20180912.004. View

11.

Siikala E, Rautemaa R, Richardson M, Saxen H, Bowyer P, Sanglard D . Persistent Candida albicans colonization and molecular mechanisms of azole resistance in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) patients. J Antimicrob Chemother. 2010; 65(12):2505-13. DOI: 10.1093/jac/dkq354. View

12.

Van Daele R, Spriet I, Wauters J, Maertens J, Mercier T, Van Hecke S . Antifungal drugs: What brings the future?. Med Mycol. 2019; 57(Supplement_3):S328-S343. DOI: 10.1093/mmy/myz012. View

13.

Flowers S, Colon B, Whaley S, Schuler M, Rogers P . Contribution of clinically derived mutations in ERG11 to azole resistance in Candida albicans. Antimicrob Agents Chemother. 2014; 59(1):450-60. PMC: 4291385. DOI: 10.1128/AAC.03470-14. View

14.

Marchaim D, Lemanek L, Bheemreddy S, Kaye K, Sobel J . Fluconazole-resistant Candida albicans vulvovaginitis. Obstet Gynecol. 2012; 120(6):1407-14. DOI: 10.1097/aog.0b013e31827307b2. View

15.

Maciel E Silva A, Viana Pereira V, Takahashi J, Silva R, Duarte L . Microwave-assisted synthesis of borneol esters and their antimicrobial activity. Nat Prod Res. 2017; 32(14):1714-1720. DOI: 10.1080/14786419.2017.1399380. View

16.

Joo H, Kim K, Myoung K, Ahn Y, Lee J, Huh C . Lactobacillus helveticus HY7801 ameliorates vulvovaginal candidiasis in mice by inhibiting fungal growth and NF-κB activation. Int Immunopharmacol. 2012; 14(1):39-46. DOI: 10.1016/j.intimp.2012.05.023. View

17.

Ramage G, Vande Walle K, Wickes B, Lopez-Ribot J . Standardized method for in vitro antifungal susceptibility testing of Candida albicans biofilms. Antimicrob Agents Chemother. 2001; 45(9):2475-9. PMC: 90680. DOI: 10.1128/AAC.45.9.2475-2479.2001. View

18.

Xu Y, Quan H, Wang Y, Zhong H, Sun J, Xu J . Requirement for Ergosterol in Berberine Tolerance Underlies Synergism of Fluconazole and Berberine against Fluconazole-Resistant Isolates. Front Cell Infect Microbiol. 2017; 7:491. PMC: 5712545. DOI: 10.3389/fcimb.2017.00491. View

19.

Shin D, Eom Y . Zerumbone inhibits biofilm formation and hyphal growth. Can J Microbiol. 2019; 65(10):713-721. DOI: 10.1139/cjm-2019-0155. View

20.

Li M, Chen Q, Shen Y, Liu W . Candida albicans phospholipomannan triggers inflammatory responses of human keratinocytes through Toll-like receptor 2. Exp Dermatol. 2009; 18(7):603-10. DOI: 10.1111/j.1600-0625.2008.00832.x. View