Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, PR China.
Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, Zhejiang, 310014, PR China; Zhejiang Provincial Key Laboratory of TCM for Innovative R & D and Digital Intelligent Manufacturing of TCM Great Health Products. Huzhou, Zhejiang Province, 313000, PR China.
J Ethnopharmacol. 2024 Sep 15;331:118274. doi: 10.1016/j.jep.2024.118274. Epub 2024 Apr 30.
ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with reproductive dysfunction and metabolic abnormalities, particularly characterized by insulin resistance and chronic low-grade inflammation. Multiple clinical studies have clearly demonstrated the significant efficacy and safety of the combination of Bailing capsules (BL) in the treatment of PCOS, but its pharmacological effects and mechanisms still require further study. AIM OF THE STUDY: To evaluate the effect of BL on improving PCOS in mice and explore the mechanism. METHODS: In this study, Dehydroepiandrosterone (DHEA) injection was administered alone and in combination with a high-fat and high-sugar diet to induce PCOS-like mouse. They were randomly divided into five groups: normal group (N), PCOS group (P), Bailing capsule low-dose group (BL-L), Bailing capsule high-dose group (BL-H) and Metformin + Daine-35 group (M + D). Firstly, the effects of BL on ovarian lesions, serum hormone levels, HOMA-IR, intestinal barrier function, inflammation levels, along with the expression of IRS1, PI3K, AKT, TLR4, Myd88, NF-κB p65, TNF-α, IL-6, and Occludin of the ovary, liver and colon were investigated. Finally, the composition of the gut microbiome of fecal was tested. RESULTS: The administration of BL significantly reduced body weight, improved hormone levels, improved IR, and attenuated pathological damage to ovarian tissues, up-regulated the expression of IRS1, PI3K, and AKT in liver. It also decreased serum LPS, TNF-α, and IL-6 levels, while downregulating the expression of Myd88, TLR4, and NF-κB p65. Additionally, BL improved intestinal barrier damage and upregulated the expression of Occludin. Interestingly, the abundance of norank_f__Muribaculacea and Lactobacillus was down-regulated, while the abundance of Akkermansia was significantly up-regulated. CONCLUSION: The results of the study showed that BL exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota, the improvement of insulin resistance and the intestinal-derived LPS-TLR4 inflammatory pathway. Our research will provide a theoretical basis for the clinical treatment of PCOS.
民族药理学相关性：多囊卵巢综合征（PCOS）是一种常见的内分泌紊乱疾病，与生殖功能障碍和代谢异常有关，特别是表现为胰岛素抵抗和慢性低度炎症。多项临床研究清楚地表明，百灵胶囊（BL）联合治疗 PCOS 的疗效和安全性显著，但其药理作用和机制仍需进一步研究。
研究目的：评估 BL 改善 PCOS 模型小鼠的作用，并探讨其作用机制。
研究方法：本研究采用脱氢表雄酮（DHEA）注射联合高脂高糖饮食诱导 PCOS 样小鼠，将其随机分为 5 组：正常组（N）、PCOS 组（P）、百灵胶囊低剂量组（BL-L）、百灵胶囊高剂量组（BL-H）和二甲双胍+达英-35 组（M+D）。首先观察 BL 对卵巢病变、血清激素水平、HOMA-IR、肠道屏障功能、炎症水平及 IRS1、PI3K、AKT、TLR4、Myd88、NF-κB p65、TNF-α、IL-6 表达的影响，然后检测卵巢、肝脏和结肠中 Occludin 的表达。最后检测粪便中肠道微生物组成。
研究结果：BL 可显著降低体重，改善激素水平，改善胰岛素抵抗，减轻卵巢组织病理损伤，上调肝脏 IRS1、PI3K 和 AKT 的表达。还降低了血清 LPS、TNF-α 和 IL-6 水平，下调了 Myd88、TLR4 和 NF-κB p65 的表达。此外，BL 改善了肠道屏障损伤，上调了 Occludin 的表达。有趣的是，norank_f__Muribaculacea 和 Lactobacillus 的丰度降低，而 Akkermansia 的丰度显著增加。
结论：研究结果表明，BL 对 PCOS 具有治疗作用，这可能与调节肠道微生物群、改善胰岛素抵抗和肠道来源的 LPS-TLR4 炎症途径有关。本研究为 PCOS 的临床治疗提供了理论依据。
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