Baofukang suppository promotes the repair of vaginal epithelial cells in response to Candida albicans

Li et al. AMB Expr Baofukang suppository promotes the repair of vaginal epithelial cells in response to Candida albicans Ting Li 0 Xiaoxi Niu 0 Xu Zhang Suxia Wang Zhaohui Liu 0 0 Department of Obstetrics and Gynecology, Peking University First Hospital , 8 Xishiku Street, Xicheng District, Beijing 100034 , China Vulvovaginal candidiasis (VVC) is an opportunistic fungal infection predominantly caused by Candida albicans affecting a significant number of women of reproductive age. The Chinese medicine, the Baofukang suppository is widely used in the clinic for its antimicrobial activity and is therefore of great interest as a potential antifungal drug for the prevention of VVC. We evaluated the cytotoxic activity of the Baofukang suppository using the VK2/E6E7 vaginal epithelial cell (VEC) line. When treated with the Baofukang suppository, all of the immunocompetent cytokines and chemokines (e.g., IL-2, IL-4, IL-6, IL-8, and IL-17) by infected VK2/E6E7 cells was statistically up-regulated (P < 0.05), except IL-4 (11.70 ± 1.82 vs. 14.88 ± 4.72, P = 0.343) compared to the infected control cells. The secretion of non-B IgG also exhibited the same trend. Our scanning electron microscopy results revealed that C. albicans can invade VECs by both induced endocytosis and active penetration. The Baofukang suppository could effectively inhibit the adhesion, hyphal formation, and proliferation, as well as notably restore the vaginal epithelial cell morphology, viability, and enhance the local immune function of the VECs. These preliminary results suggest promising antimicrobial properties of the Baofukang suppository, which may be efficacious as an antifungal therapy candidate via up-regulating Th1 cellular immunity, the Th17-axis of the innate immune response, and the secretion of vaginal epithelial-derived IgG. These combined effects collectively restore the immune function of the infected VECs against C. albicans in vitro. Vulvovaginal candidiasis; Vaginal epithelial cells; Candida albicans; Baofukang suppository; Cytokines - Introduction The majority of women experience at least one episode of vulvovaginal candidiasis (VVC) in their lifetime (Sobel et al. 1998). The vaginal epithelium as a mucosal surface is of immense importance in host defense and immune surveillance (Moyes et al. 2011). Specifically, it functions as the first line of host defense against pathogen invasion to provide a physical barrier and protect underlying tissues and organs (Cole 2006). Products containing essential oils have been formulated for intra-vaginal use, and are often recommended as home remedies for the treatment of vaginal candidiasis by published books and articles (Marti and Hine 1995; Newall et al. 1996). Baofukang suppository is a type of traditional Chinese medicine that consists primarily of two Chinese Medicinal Herbs: (1) zedoary turmeric oil; and (2) borneol. Zedoary turmeric oil is a volatile oil steamdistilled from Curcuma phaeocaulis which contains a variety of effective components, including beta-elemene, curcumin, curzerenone, and Zimmer ketones currently in clinical use. These components may provide potent pharmacological activities, such as antitumor or antiviral effects, enhancing the immune response, particularly by promoting the regeneration and repair of damaged or inflamed mucosa (Kamazeri et al. 2012). Due to its potent pharmacological action, this plant extract has begun to attract some significant attention. Borneol is extracted from the essential oil of various subtropical and evergreen broad-leaved such as Cinnamomum and Lauraceae, and a bicyclic monoterpenoid alcohol commonly © The Author(s) 2016. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. used in traditional Chinese medicine as the adjuvant for more than 1500 years (Jiang et al. 2008). It demonstrates anti-inflammatory, analgesic, and antibacterial properties, while also accelerating percutaneous drug absorption and increasing the bioavailability of drugs in the brain tissue (Almeida et  al. 2013; Slamenova et  al. 2009). Therefore, the aims of this work was to evaluate the in vitro antifungal properties and mechanisms of the Baofukang suppository, which would be further applied widely in clinic as a potential antifungal drug for the prevention of VVC. Materials and methods Vaginal epithelial cell culture The VK2/E6E7 vaginal epithelial cell line (ATCC® CRL2616), obtained from the American Type Culture Collection (ATCC; Rock ville, MD, USA) is an epithelial cell line derived from the vaginal mucosa of a healthy premenopausal female undergoing vaginal repair surgery, that was subsequently immortalized wit (...truncated)