Therapeutic Potential of Perillaldehyde in Ameliorating Vulvovaginal Candidiasis by Reducing Vaginal Oxidative Stress and Apoptosis.

Lei Chen,Yong-Xin Li,Xue Peng,Man Liu,Jun Tian,Yi Zhou,Su Qu,Kunlong Yang,Yongxin Zhu,Fei Wang,Xiaona He

doi:10.3390/antiox11020178

Abstract

Vulvovaginal candidiasis (VVC) is one of the most frequent diseases induced by Candida albicans (C. albicans) during pregnancy, which results in enormous pain to women and their partners in daily life. Perillaldehyde (PAE), a natural monoterpenoid, has significant anti-microbial, anti-inflammatory and anti-oxidation effects. Reactive oxygen species (ROS) are key factors for the host to resist the invasion of fungi. However, excess ROS can cause additional damage independent of the pathogen itself, and the mechanism of ROS in VVC has not been investigated. In this murine study, we revealed that C. albicans infection increased the expression of NADPH oxidase 2 (NOX2) and the content of malonaldehyde (MDA). C. albicans inhibited the activity of antioxidant enzymes in the vagina, including superoxide dismutase (SOD), Catalase (CAT), glutathione peroxidase (GSH-PX) and heme oxygenase (HO-1), which were returned to normal levels after treatment with PAE. Furthermore, PAE inhibited the activities of Keap1 and promoted Nrf2 transfer from cytoplasm to nucleus, which were mediated by excessive accumulation of ROS in the VVC mice. In this study, we also indicated that PAE inhibited the apoptosis of vagina cells via Caspase 9- Caspase 7-PARP pathway and prevented the release of IL-1ꞵ in VVC mice. In summary, this study revealed that the treatment of VVC in mice with PAE might be mediated by inhibition of ROS, and established the therapeutic potential of PAE as an antifungal agent for the treatment of VVC.

Highlights

Vulvovaginal candidiasis (VVC) is a pervasive disease caused by a symbiotic fungusCandida albicans (C. albicans), which has been previously shown to be parasitic on the mucosal surface
We found that the expression of Keap1 in the Ca group mice was increased in a statistically significant manner, and this implies that a large amount of Nuclear factor E2 related factor 2 (Nrf2) is trapped in its cytoplasm thence causing the inhibition of the oxidative stress response in VVC mice with a tendency of creating oxidative damage in the vaginal cells
Our study showed that C. albicans infection can lead to overexpression of intravaginal BAX and the inhibition of Bcl-2, thereby activating Caspase 9, which is the initiator of apoptosis

Summary

Introduction

Vulvovaginal candidiasis (VVC) is a pervasive disease caused by a symbiotic fungusCandida albicans (C. albicans), which has been previously shown to be parasitic on the mucosal surface. Vulvovaginal candidiasis (VVC) is a pervasive disease caused by a symbiotic fungus. The use of high-estrogen oral contraceptive, hormone replacement therapy, misuse of antibiotic, and the emergence of a large number of diabetic female patients, have contributed to the increasing prevalence and recurrence of VVC [2]. About 75% of women are afflicted by VVC at least once in their life time, especially during the childbearing age and menstrual cycle when their estrogen level is elevated. Estimated suggest that 5–8% of women (about 150 million all over the world) suffer from recurrent invasion of C. albicans, which effectuates great affliction to their daily life, as well as causing great challenges to their clinical treatment [3].

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