Abstract
In the past few years, emerging evidence established persistent oxidative stress to be a key player in the pathogenesis of polycystic ovary syndrome (PCOS). Particularly, it damages the function of granulosa cells, and thus hinders the development of follicles. The present study aimed to explore and establish the protective effects of salidroside on dihydrotestosterone (DHT)‐induced Granulosa‐like tumor cell line (KGN), mediated via antioxidant mechanisms. The study assessed the positive effects of salidroside on DHT‐induced apoptosis, reactive oxygen species (ROS) accumulation, damage of antioxidant capacity, and mitochondrial membrane potential depolarization. Interestingly, salidroside partly reversed DHT mediated effects, via stimulation of nuclear factor erythroid 2‐related factor 2 (Nrf2) signaling pathway and the downstream antioxidant proteins heme oxygenase‐1(HO‐1) and quinine oxidoreductase 1(NQO1). Additionally, the knockdown of Nrf2 partly moderated the antioxidant and anti-apoptosis effects of salidroside in DHT-treated KGN cells. Mechanistically, AMP‐activated protein kinase (AMPK) was identified to be the upstream signaling involved in salidroside‐induced Nrf2 activation, as silencing of AMPK partly prevented the upregulation of Nrf2 and the downstream proteins HO‐1 and NQO1. Altogether, the present study is the first to effectively demonstrate the inhibitory effect of salidroside on DHT‐stimulated oxidative stress and apoptosis in KGN cells, which was dependent on Nrf2 activation that involved AMPK.
Highlights
Granulosa cells constitute the cell layer present in the follicles that interact with oocytes and mediate the metabolism, transport of materials, and signal transduction in oocytes
Several female reproductive endocrine diseases related to hormonal changes and follicular development, such as premature ovarian failure and polycystic ovary syndrome (PCOS), are associated with abnormal changes in granulosa cells, which are known to be involved in the disease developmental process[2, 3]
The present study aimed to explore whether salidroside can incur a protective effect on suppressing the oxidative stress and apoptosis in DHT-induced KGN, and unravel the underlying mechanism responsible for its functions in KGN cells
Summary
Granulosa cells constitute the cell layer present in the follicles that interact with oocytes and mediate the metabolism, transport of materials, and signal transduction in oocytes. These cells play a crucial role in follicular growth, proliferation, differentiation, atresia/ovulation, and formation of the corpus luteum[1]. In the past few years, emerging evidence established persistent oxidative stress to be a key player in the pathogenesis of polycystic ovary syndrome (PCOS). It damages the function of granulosa cells, and hinders the development of follicles. The present study aimed to explore and establish the protective effects of salidroside on dihydrotestosterone (DHT)‐induced Granulosa‐like tumor cell line (KGN), mediated via antioxidant mechanisms
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