Liu Haijuan, Wang Guohua, Sui Conglu, Guo Yanan, He Xiangyu
Department of Gynecology, Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, 100029, China.
Department of Traditional Chinese Medicine, Northwest Women's and Children's Hospital, Xi'an, 710061, China.
J Ovarian Res. 2025 Jan 16;18(1):7. doi: 10.1186/s13048-025-01587-5.
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women of reproductive age. Anovulation is one of the most important clinical features of PCOS, and insulin resistance (IR) is one of the critical pathogenic factors. Woxuanzhongzhou (WXZZ) is a traditional herbal formulation that has shown efficacy in treating PCOS combined with IR, but the underlying mechanism is not clear. The aim of this study was to investigate the molecular mechanism of WXZZ on dehydroepiandrosterone sulfate and high fat diet induced PCOS with IR mice.
40 female C57BL/6 mice were randomized to 4 groups: control group, model group, metformin group, and WXZZ group. Some mice is induced by dehydroepiandrosterone sulfate (DHEA) and high-fat diet (HFD) for 3 weeks. Following model induction, metformin and WXZZ were administered by gavage. Body weight, fasting blood glucose (FBG), fasting insulin (FINS) levels, the homeostatic model assessment of insulin resistance (HOMA-IR), and gonadal hormones were measured. Estrous cycles were monitored. The structure of the gastrocnemius muscle and subcutaneous fatty tissue were also evaluated. Additionally, serum irisin and non-esterified fatty acids (NEAF) levels and the protein and gene expression levels of AMPK, PGC1-α, FNDC5, irisin in the gastrocnemius muscle and CaMKK, AMPK, PGC1-α, UCP1 in fat were analyzed.
The DHEA + HFD + WXZZ group exhibited significant improvements in several key parameters compared to the DHEA + HFD group. WXZZ ameliorated endocrine and metabolic disorders, resumed estrous cycle in DHEAS and high-fat diet-induced IR and anovulatory mice. Significant reductions were observed in body weight, serum testosterone, luteinizing hormone, luteinizing hormone/ follicle-stimulating hormone ratio, FINS, and HOMA-IR. Additionally, WXZZ promoted irisin expression and secretion by up-regulating the protein and gene AMPK/PGC1-α/FNDC5 expression in gastrocnemius muscle and up-regulated the protein and gene CaMKK/AMPK/PGC1-α/UCP1 expression in fat. WXZZ inhibited the overproduction of serum NEFA, and reduced lipid accumulation. Structural analysis of the gastrocnemius muscle and adipose tissue revealed partial restoration.
WXZZ exhibits therapeutic effects in DHEAS and high-fat diet-induced IR and anovulatory mice. These effects may be mediated through the activation of AMPK/PGC1-α pathway in muscle to promote the secretion of irisin.
多囊卵巢综合征（PCOS）是育龄期女性常见的内分泌和代谢紊乱疾病。无排卵是PCOS最重要的临床特征之一，胰岛素抵抗（IR）是关键的致病因素之一。沃 Xuanzhongzhou（WXZZ）是一种传统草药配方，已显示出对合并IR的PCOS有治疗效果，但其潜在机制尚不清楚。本研究旨在探讨WXZZ对硫酸脱氢表雄酮和高脂饮食诱导的伴有IR的PCOS小鼠的分子机制。
将40只雌性C57BL/6小鼠随机分为4组：对照组、模型组、二甲双胍组和WXZZ组。部分小鼠用硫酸脱氢表雄酮（DHEA）和高脂饮食（HFD）诱导3周。模型诱导后，通过灌胃给予二甲双胍和WXZZ。测量体重、空腹血糖（FBG）、空腹胰岛素（FINS）水平、胰岛素抵抗稳态模型评估（HOMA-IR）和性腺激素。监测发情周期。还评估了腓肠肌和皮下脂肪组织的结构。此外，分析了血清鸢尾素和非酯化脂肪酸（NEAF）水平以及腓肠肌中AMPK、PGC1-α、FNDC5、鸢尾素的蛋白和基因表达水平，以及脂肪中CaMKK、AMPK、PGC1-α、UCP1的情况。
与DHEA + HFD组相比，DHEA + HFD + WXZZ组在几个关键参数上有显著改善。WXZZ改善了内分泌和代谢紊乱，使DHEAS和高脂饮食诱导的IR和无排卵小鼠恢复了发情周期。体重、血清睾酮、黄体生成素、黄体生成素/卵泡刺激素比值、FINS和HOMA-IR均显著降低。此外，WXZZ通过上调腓肠肌中蛋白和基因AMPK/PGC1-α/FNDC5的表达促进鸢尾素的表达和分泌，并上调脂肪中蛋白和基因CaMKK/AMPK/PGC1-α/UCP1的表达。WXZZ抑制了血清NEFA的过量产生，并减少了脂质积累。腓肠肌和脂肪组织的结构分析显示部分恢复。
WXZZ对DHEAS和高脂饮食诱导的IR和无排卵小鼠具有治疗作用。这些作用可能是通过激活肌肉中的AMPK/PGC1-α途径来促进鸢尾素的分泌介导的。
