Jiao-tai-wan and its component coptisine attenuate PCOS by regulating mitochondrial cholesterol import through suppression of SIRT1 ubiquitination
Abstract
BACKGROUND: Polycystic ovary syndrome (PCOS) has emerged as a common endocrine disorder that impacts female reproductive health. The traditional herbal formulation, Jiao-tai-wan (JTW), exhibits multiple biological activities, including improving insulin resistance, reducing oxidative stress, and mitigating inflammation. The clinical efficacy of JTW against PCOS has been reported, however, mechanistic studies remain absent.
PURPOSE: To clarify the mechanisms behind the therapeutic efficacy of JTW in PCOS.
METHODS: The PCOS rat model was established by injection of DHEA. The in vivo study consisted of two parts: Part 1 included control, PCOS, low-dose JTW, high-dose JTW, and metformin (Glucophage) groups; Part 2 included control, PCOS, and coptisine groups. The in vitro study utilized primary theca cells. The effects of JTW on ameliorating PCOS phenotypes were assessed. Key pathways were identified via RNA sequencing, and the primary constituents of JTW were identified using UPLC fingerprinting. Further mechanistic investigations were conducted using techniques including network pharmacology, cell transfection, transmission electron microscopy imaging, confocal imaging, co-immunoprecipitation, CETSA, and SPR.
RESULTS: JTW attenuated abnormal ovulation, sex hormone imbalance, glycolipid metabolism disorders, and oxidative stress in PCOS rats. RNA sequencing revealed that JTW regulated the ovarian steroidogenesis pathway. Furthermore, JTW regulated mitochondrial dynamics and…
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