PDF(Pubmed)
Abstract：
Vulvovaginal candidiasis (VVC) is an infectious disease caused by Candida 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 Candida 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 Candida albicans (C. albicans) and the anti-inflammatory mechanism correlated with the Dectin-1 signaling pathway. In vivo and in vitro results showed that KBN had strong antifungal and anti-inflammatory effects in FLC-resistant VVC, such as inhibiting the growth of C. albicans 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 ERG11, and reduced the expression of drug-resistant efflux pump genes MDR1 and CDR2 of FLC-resistant C. albicans in vitro. In addition, in vivo 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 C. albicans. This effect may be related to inhibiting the growth of FLC-resistance C. albicans and Dectin-1 signaling pathway activation.
摘要：
外阴阴道念珠菌病(VVC)是一种由念珠菌引起的感染性疾病,每年影响全世界数百万女性。对可用于临床治疗的抗真菌药物的耐药性是一个日益严重的问题。由唑类耐药念珠菌引起的难治性VVC的治疗仍面临挑战。然而,抗真菌新药的研究进展缓慢。虽然很多关于抗真菌新药的报道,只有三种新的抗真菌药物（伊沙康康唑，Ibrexafungerp,和rezafungin）和泊沙康唑的两种新制剂在过去十年中上市。中草药在治疗耐药VVC方面具有优势,如疗效突出,不良反应少,这可以提高患者的舒适度和对治疗的依从性。康巴尼亚乳液（KBN），一种中国植物配方，在治疗VVC方面取得了很好的临床效果。在这项研究中,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耐药白色念珠菌的抗真菌机制（C.白色念珠菌）和与Dectin-1信号通路相关的抗炎机制。体内和体外结果表明，KBN对FLC耐药的VVC具有较强的抗真菌和抗炎作用，如抑制白色念珠菌的生长和阴道炎症。进一步的研究表明，KBN抑制生物膜和菌丝的形成，降低附着力,体外抑制FLC耐药白色念珠菌的麦角甾醇合成和麦角甾醇合成相关基因ERG11的表达，降低耐药外排泵基因MDR1和CDR2的表达。此外,体内结果显示,KBN降低炎症因子蛋白TNF-α的表达,IL-1β,和阴道组织中的IL-6，并抑制Dectin-1信号通路相关蛋白的表达。总之,我们的研究表明，KBN可以改善由FLC抗性白色念珠菌引起的VVC小鼠的阴道炎症。这种作用可能与抑制FLC抗性白色念珠菌的生长和Dectin-1信号通路的激活有关。
