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网络药理学与实验验证以阐明血竭治疗胰岛素抵抗型多囊卵巢综合征的机制

Network pharmacology and experimental validation to elucidate the mechanism of the treatment of polycystic ovary syndrome with insulin resistance by Resina Draconis.

作者信息

Wang Jing, Luo Yehao, Liu Yueting, Tang Xiusong, Gu Jianhui, Huang Zheng, Lv Ting, Luo Jun, Fang Gang

机构信息

Guangxi Key Laboratory for Applied Fundamental Research of Zhuang Medicine-Key Laboratory Project under Guangxi Health Commission, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530001, China.

Guangxi Higher Education Key Laboratory for the Research of Du-related Diseases in Zhuang Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530200, China.

出版信息

J Ovarian Res. 2025 May 24;18(1):108. doi: 10.1186/s13048-025-01685-4.

DOI:10.1186/s13048-025-01685-4
PMID:40413545
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12102831/
Abstract

BACKGROUND

Resina Draconis(RD) is a traditional Chinese medicine that activates blood circulation and removes blood stasis. Modern pharmacological studies have proved that RD has hypoglycaemic, pancreatic islets-protective, oestrogenic activity, anti-inflammatory, antibacterial and anti-tumour effects. Studies have shown that insulin resistance (IR) is the core pathological mechanism of polycystic ovary syndrome (PCOS), and RD can lower blood glucose to ameliorate IR, which has achieved significant results in the treatment of diabetes. However, the mechanism of action of RD in the treatment of PCOS-IR is still unclear.

METHODS

Network pharmacology analysis was used to predict the potential therapeutic targets of the active ingredients of RD. Experimental validation used a rat model of insulin resistance in PCOS; PCOS-IR symptoms were assessed, ovarian pathology was evaluated, and serum levels of insulin and sex hormones were determined. Expression levels of the PI3K, p-PI3K, Akt, p-Akt, GLUT4, FOXO3a, and P27 proteins were also measured in rat ovaries, along with mRNA expression levels of PI3K, Akt, GLUT4, FOXO3a, and P27.

RESULTS

Network pharmacological analyses indicated that the PI3K/Akt signalling pathway may play an important role in the treatment of PCOS-IR rats with RD. Experiments in PCOS-IR rats showed that RD significantly reversed insulin resistance, improved pathological changes in the ovaries, increased serum levels of follicle stimulating hormone (FSH) and estradiol (E2), and decreased levels of luteinizing hormone (LH), testosterone (T) and insulin. In addition, RD increased the levels of PI3K, p-PI3K, Akt, p-Akt and GLUT4, and decreased the levels of FOXO3a and P27 in the ovarian tissues of PCOS-IR rats, suggesting that RD may improve the symptoms of PCOS-IR in rats through the PI3K/Akt signalling pathway.

CONCLUSION

RD might improve insulin resistance and ovarian function in PCOS-IR by upregulating PI3K, p-PI3K, Akt, p-Akt and GLUT4 expression and downregulating FOXO3a and P27, thereby activating the PI3K/Akt signaling pathway. RD also regulated the LH/FSH ratio, increased E2 levels, reduced LH and T levels, and alleviated PCOS-IR symptoms in a rat PCOS-IR model.

摘要

背景

血竭是一种活血化瘀的传统中药。现代药理学研究证明,血竭具有降血糖、保护胰岛、雌激素活性、抗炎、抗菌和抗肿瘤作用。研究表明,胰岛素抵抗(IR)是多囊卵巢综合征(PCOS)的核心病理机制,血竭可降低血糖以改善IR,在糖尿病治疗中已取得显著效果。然而,血竭治疗PCOS-IR的作用机制仍不清楚。

方法

采用网络药理学分析预测血竭活性成分的潜在治疗靶点。实验验证采用PCOS胰岛素抵抗大鼠模型;评估PCOS-IR症状,评价卵巢病理变化,并测定胰岛素和性激素的血清水平。还测定了大鼠卵巢中PI3K、p-PI3K、Akt、p-Akt、GLUT4、FOXO3a和P27蛋白的表达水平,以及PI3K、Akt、GLUT4、FOXO3a和P27的mRNA表达水平。

结果

网络药理学分析表明,PI3K/Akt信号通路可能在血竭治疗PCOS-IR大鼠中起重要作用。PCOS-IR大鼠实验表明,血竭显著逆转胰岛素抵抗,改善卵巢病理变化,提高血清促卵泡生成素(FSH)和雌二醇(E2)水平,并降低黄体生成素(LH)、睾酮(T)和胰岛素水平。此外,血竭增加了PCOS-IR大鼠卵巢组织中PI3K、p-PI3K、Akt、p-Akt和GLUT4的水平,并降低了FOXO3a和P27的水平,表明血竭可能通过PI3K/Akt信号通路改善大鼠PCOS-IR症状。

结论

血竭可能通过上调PI3K、p-PI3K、Akt、p-Akt和GLUT4表达以及下调FOXO3a和P27来改善PCOS-IR中的胰岛素抵抗和卵巢功能,从而激活PI3K/Akt信号通路。血竭还调节了LH/FSH比值,提高了E2水平,降低了LH和T水平,并减轻了大鼠PCOS-IR模型中的PCOS-IR症状。

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