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康百年洗液通过抑制耐氟康唑菌株生长及激活Dectin-1信号通路改善小鼠外阴阴道念珠菌病

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

作者信息

Chen Zewei, Luo Tengshuo, Huang Fengke, Yang Fuzhen, Luo Wenting, Chen Guanfeng, Cao Mengfei, Wang Fengyun, Zhang Jun

机构信息

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.

School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China.

出版信息

Front Pharmacol. 2022 Jan 20;12:816290. doi: 10.3389/fphar.2021.816290. eCollection 2021.

DOI:10.3389/fphar.2021.816290
PMID:35140608
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8819624/
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.

摘要

外阴阴道假丝酵母菌病(VVC)是一种由特定菌种引起的传染病,每年影响着全球数百万女性。临床治疗中对现有抗真菌药物的耐药性是一个日益严重的问题。由耐唑类假丝酵母菌引起的难治性VVC的治疗仍面临挑战。然而,新型抗真菌药物的研究进展缓慢。尽管有很多关于新型抗真菌药物的报道,但在过去十年中,只有三种新型抗真菌药物(艾沙康唑、ibrexafungerp和瑞扎芬净)以及泊沙康唑的两种新剂型上市。中药在治疗耐药性VVC方面具有优势,如疗效显著且不良反应低,可提高患者的舒适度和治疗依从性。康百年洗液(KBN)是一种中药制剂,在治疗VVC方面取得了很好的临床效果。在本研究中,我们研究了不同剂量的KBN在氟康唑耐药(FLC耐药)VVC模型小鼠中的抗真菌和抗炎作用。我们进一步研究了KBN对FLC耐药白色念珠菌(白色念珠菌)的抗真菌机制以及与Dectin-1信号通路相关的抗炎机制。体内和体外结果表明,KBN在FLC耐药VVC中具有强大的抗真菌和抗炎作用,如抑制白色念珠菌生长和阴道炎症。进一步研究表明,KBN抑制生物膜和菌丝形成,减少黏附,抑制麦角固醇合成以及麦角固醇合成相关基因ERG11和ERG3的表达,并降低FLC耐药白色念珠菌耐药外排泵基因CDR1和MDR1的表达。此外,体内结果表明,KBN降低了阴道组织中炎性因子蛋白TNF-α、IL-1β和IL-6的表达,并抑制了与Dectin-1信号通路相关的蛋白表达。总之,我们的研究表明,KBN可以改善由FLC耐药白色念珠菌引起的VVC小鼠的阴道炎症。这种作用可能与抑制FLC耐药白色念珠菌生长和激活Dectin-1信号通路有关。

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