Yang Wanqi, Qiu Jishuang, Zi Jiangli, Li Yang, Li Jiao, Guo Meixian, Zhou Yanru, Yang Xiaotong, Lai Yong
Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, College of Pharmacy, Dali University, Dali, Yunnan, PR China; College of Pharmacy, Dali University, Dali, Yunnan, PR China; National-Local Joint Engineering Research Center of Entomoceutics, Dali University, Dali, Yunnan Province, PR China.
Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, College of Pharmacy, Dali University, Dali, Yunnan, PR China; College of Pharmacy, Dali University, Dali, Yunnan, PR China.
J Ethnopharmacol. 2025 Feb 10;338(Pt 1):119020. doi: 10.1016/j.jep.2024.119020. Epub 2024 Nov 2.
Abnormal endocrine metabolism caused by polycystic ovary syndrome (PCOS) poses a serious risk to reproductive health in females. According to Traditional Chinese Medicine (TCM) theories, the leading causes of PCOS include turbid phlegm, blood stasis and stagnation of liver Qi. Rhei Radix Et Rhizome is widely used in TCM to attack stagnation, clear damp heat, relieve fire. Rhei Radix Et Rhizome is an important part of the TCM formulas for the treatment of PCOS, which has a long history of medicinal use. However, the specific effect and mechanisms of Rhei Radix Et Rhizome on PCOS have yet to be elucidated.
The object of this study aimed to investigate the effect and its pharmacological mechanism of Rhei Radix Et Rhizome on the treatment of polycystic ovary syndrome.
PCOS was induced in female Sprague Dawley (SD) rats by administering letrozole (1 mg/kg, per orally, p.o.) for 21 days, then treated with Rhei Radix Et Rhizome at doses of 0.6 g/kg or 1.2 g/kg. Rats weight, blood glucose and estrus period are measured, and serum hormone include free testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and ovarian lesions were observed to determine the effects of Rhei Radix Et Rhizome. Network pharmacology and molecular docking predicted the targets of Rhei Radix Et Rhizome on PCOS. Epidermal growth factor receptor (EGFR), albumin (ALB), PI3K and P-AKT/AKT protein expression levels in ovarian tissues were assessed by Western blot.
Rhei Radix Et Rhizome reduce abnormal weight and fasting blood glucose induced by letrozole (n = 5, p < 0.01), and improve the disturbed estrus cycle, reduce T, LH levels and LH/FSH ratio of PCOS rats (n = 4, p < 0.01). In addition, it alleviates the polycystic changes of ovaries in PCOS rats and reduces ovarian histopathological damage (n = 4, p < 0.01). Additionally, the core active components of Rhei Radix Et Rhizome for PCOS include Sennoside D_qt, Procyanidin B-5,3'-O-gallate, and Mutatochrome, which strongly bind to core therapeutic targets ALB and EGFR. Furthermore, the treatment reduces the increase of EGFR and ALB induced by letrozole (n = 4, p < 0.01). KEGG pathway enrichment analysis highlights endocrine resistance and prolactin signaling pathway, in both of which the PI3K/AKT pathway plays a crucial role. Our results show Rhei Radix Et Rhizome rescue the abnormal expression of PI3K/AKT pathway in PCOS rats (n = 4, p < 0.01). However, no significant dose-dependent relationship was observed in the tested dose range for the above experiments.
These findings suggest that Rhei Radix Et Rhizome can regulate the PI3K/AKT pathway and target EGFR and ALB to treat polycystic ovary syndrome in rats. This study provides a scientific basis for the use of Rhei Radix Et Rhizome in the treatment of PCOS and highlights its potential mechanism through modulation of the PI3K/AKT pathway.
多囊卵巢综合征（PCOS）引起的内分泌代谢异常对女性生殖健康构成严重风险。根据中医理论，PCOS的主要病因包括痰湿、血瘀和肝郁气滞。大黄根茎在中医中广泛用于攻积滞、清湿热、泻火。大黄根茎是治疗PCOS的中药方剂的重要组成部分，药用历史悠久。然而，大黄根茎对PCOS的具体作用和机制尚待阐明。
本研究旨在探讨大黄根茎治疗多囊卵巢综合征的作用及其药理机制。
通过给予来曲唑（1mg/kg，口服）21天诱导雌性Sprague Dawley（SD）大鼠患PCOS，然后分别用0.6g/kg或1.2g/kg剂量的大黄根茎进行治疗。测量大鼠体重、血糖和发情周期，并观察血清激素包括游离睾酮（T）、黄体生成素（LH）、卵泡刺激素（FSH）以及卵巢病变，以确定大黄根茎的作用。网络药理学和分子对接预测大黄根茎对PCOS的靶点。通过蛋白质免疫印迹法评估卵巢组织中表皮生长因子受体（EGFR）、白蛋白（ALB）、PI3K和P-AKT/AKT蛋白表达水平。
大黄根茎可减轻来曲唑诱导的体重异常和空腹血糖（n = 5，p < 0.01），改善PCOS大鼠紊乱的发情周期，降低T、LH水平及LH/FSH比值（n = 4，p < 0.01）。此外，它减轻了PCOS大鼠卵巢的多囊样改变并减少卵巢组织病理学损伤（n = 4，p < 0.01）。另外，大黄根茎治疗PCOS的核心活性成分包括番泻苷D_qt、原花青素B-5、3'-O-没食子酸酯和变色素，它们与核心治疗靶点ALB和EGFR紧密结合。此外，该治疗降低了来曲唑诱导的EGFR和ALB的升高（n = 4，p < 0.01）。KEGG通路富集分析突出了内分泌抵抗和催乳素信号通路，PI3K/AKT通路在这两条通路中均起关键作用。我们的结果表明大黄根茎可挽救PCOS大鼠中PI3K/AKT通路的异常表达（n = 4，p < 0.01）。然而，在上述实验的测试剂量范围内未观察到明显的剂量依赖性关系。
这些发现表明大黄根茎可调节PI3K/AKT通路并靶向EGFR和ALB来治疗大鼠多囊卵巢综合征。本研究为大黄根茎用于治疗PCOS提供了科学依据，并突出了其通过调节PI3K/AKT通路的潜在机制。
