Department of Obstetrics and Gynecology, Women and Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Department of Reproductive Biology, Joint International Research Laboratory of Reproduction and Development, School of Public Health, Chongqing Medical University, Chongqing, People's Republic of China.
Reproduction. 2023 Sep 28;166(5):323-336. doi: 10.1530/REP-22-0449. Print 2023 Nov 1.
Obese PCOS mice display metabolic and endocrine disorders that manifest as abnormal metabolism of glucose and dysfunctions in the reproductive system. This study demonstrates that emodin alleviates most of these conditions possibly via the HMGB1/TLR4/NF-kB pathway.
PCOS is a reproductive disorder with an unclear etiology. It affects 5-10% of women worldwide and is largely associated with impaired glucose metabolism and obesity. HMGB1 is a nuclear protein associated with impaired glucose metabolism and PCOS. We sought to investigate the potential therapeutic effects of emodin on glucose metabolism and ovarian functions in PCOS mice via the HMGB1 molecular pathway. A high-fat diet (HFD) and dehydroepiandrosterone (DHEA)- induced PCOS mouse model comprising four experimental groups was established: control, PCOS, PCOS plus emodin, and PCOS plus vehicle groups. Emodin administration attenuated obesity, elevated fasting glucose levels, impaired glucose tolerance, and insulin resistance, and improved the polycystic ovarian morphology of PCOS mice. Additionally, it lowered elevated serum HMGB1, LH, and testosterone levels in PCOS mice. Elevated ovarian protein and mRNA levels of HMGB1 and TLR4 in PCOS mice were also lowered following emodin treatment. Furthermore, emodin lowered high NF-ĸB/65 protein levels in the ovaries of PCOS mice. Immunohistochemical staining of the ovaries revealed strong HMGB1, TLR4, and AR expressions in PCOS mice, which were lowered by emodin treatment. Moreover, emodin significantly increased GLUT4, IRS2, and INSR levels that were lowered by PCOS. Overall, our study showed that emodin alleviated the impaired glucose metabolism and improved ovarian function in PCOS mice, possibly via the HMGB1/TLR4/NF-ĸB signaling pathway. Thus, emodin could be considered a potential therapeutic agent in the management of PCOS.
患有 PCOS 的肥胖小鼠表现出代谢和内分泌紊乱，其特征为葡萄糖代谢异常和生殖系统功能障碍。本研究表明，大黄素可能通过 HMGB1/TLR4/NF-κB 通路缓解这些病症。
PCOS 是一种病因不明的生殖系统疾病。它影响全球 5-10%的女性，主要与葡萄糖代谢受损和肥胖有关。HMGB1 是一种与葡萄糖代谢受损和 PCOS 相关的核蛋白。我们试图通过 HMGB1 分子通路研究大黄素对 PCOS 小鼠葡萄糖代谢和卵巢功能的潜在治疗作用。建立了包含四个实验组的高脂肪饮食（HFD）和脱氢表雄酮（DHEA）诱导的 PCOS 小鼠模型：对照组、PCOS 组、PCOS 加大黄素组和 PCOS 加载体组。大黄素给药可减轻肥胖、空腹血糖升高、葡萄糖耐量受损和胰岛素抵抗，并改善 PCOS 小鼠的多囊卵巢形态。此外，它还降低了 PCOS 小鼠血清中升高的 HMGB1、LH 和睾酮水平。大黄素还降低了 PCOS 小鼠卵巢中升高的 HMGB1 和 TLR4 蛋白和 mRNA 水平。此外，大黄素降低了 PCOS 小鼠卵巢中高 NF-κB/65 蛋白水平。卵巢免疫组化染色显示 PCOS 小鼠的 HMGB1、TLR4 和 AR 表达强烈，大黄素治疗后降低。此外，大黄素还显著增加了 PCOS 降低的 GLUT4、IRS2 和 INSR 水平。总之，我们的研究表明，大黄素可缓解 PCOS 小鼠的葡萄糖代谢受损并改善卵巢功能，可能通过 HMGB1/TLR4/NF-κB 信号通路。因此，大黄素可以被认为是管理 PCOS 的一种潜在治疗药物。
