Wu Jiaru, Wen Mengjie, Wang Zecheng, Yu Kun, Jin Xinyue, Liu Chenxu, Song Qiuhang, Zhang Guohong, Wu Beibei, Li Yunfeng
School of Integrative Medicine, Hebei University of Chinese Medicine. Shijiazhuang, Hebei, China.
School of Experimental Center, Hebei University of Chinese Medicine. Shijiazhuang, Hebei, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr;398(4):3667-3680. doi: 10.1007/s00210-024-03476-y. Epub 2024 Oct 1.
Premature ovarian failure (POF) is a disease that seriously jeopardizes women's physical and mental health worldwide. Zisheng Tongmai decoction (ZSTMD), a famous Traditional Chinese Medicine (TCM) formula, has a marked effect on the clinical treatment of POF. This study investigated the potential mechanism of ZSTMD to improve POF through network pharmacology and experimental validation. The active components, key targets and potential mechanisms of ZSTMD against POF were predicted by network pharmacology and molecular docking. The POF model was induced in rats by cyclophosphamide (CTX) and subsequently gavaged with different doses of ZSTMD. KGN cells were treated with different concentrations of quercetin and CTX. Histopathological were observed via hematoxylin and eosin (H&E) staining and immunofluorescence staining. Serum estrogen levels were detected via ELISA. Protein expression was detected via Western blot. We identified quercetin as the main active ingredients targeting VEGFA. Molecular docking showed that VEGFA interacted well with the main active components of ZSTMD. In vivo experiments, ZSTMD significantly increased body weight and the ovarian index, significantly increased E2 and AMH, and decreased FSH and LH in POF rats. Histologic results showed that ZSTMD increased the number of follicles and vascular density in the ovary. It also increased VEGFA and CD31 protein expression. In vitro experiments, quercetin suppressed CTX-induced apoptosis in KGN cells and increased VEGFA protein expression. Our study demonstrated that ZSTMD improves POF by promoting angiogenesis through VEGFA target.
卵巢早衰（POF）是一种严重危害全球女性身心健康的疾病。滋肾通脉汤（ZSTMD）是一种著名的中药方剂，对POF的临床治疗有显著效果。本研究通过网络药理学和实验验证来探究ZSTMD改善POF的潜在机制。通过网络药理学和分子对接预测ZSTMD抗POF的活性成分、关键靶点和潜在机制。用环磷酰胺（CTX）诱导大鼠建立POF模型，随后用不同剂量的ZSTMD灌胃。用不同浓度的槲皮素和CTX处理KGN细胞。通过苏木精-伊红（H&E）染色和免疫荧光染色观察组织病理学变化。通过酶联免疫吸附测定（ELISA）检测血清雌激素水平。通过蛋白质印迹法检测蛋白质表达。我们确定槲皮素是靶向血管内皮生长因子A（VEGFA）的主要活性成分。分子对接表明VEGFA与ZSTMD的主要活性成分相互作用良好。在体内实验中，ZSTMD显著增加POF大鼠的体重和卵巢指数，显著提高雌二醇（E2）和抗缪勒管激素（AMH）水平，并降低促卵泡生成素（FSH）和促黄体生成素（LH）水平。组织学结果显示，ZSTMD增加了卵巢中卵泡数量和血管密度。它还增加了VEGFA和血小板内皮细胞黏附分子-1（CD31）蛋白表达。在体外实验中，槲皮素抑制CTX诱导的KGN细胞凋亡，并增加VEGFA蛋白表达。我们的研究表明，ZSTMD通过VEGFA靶点促进血管生成来改善POF。
