Wang Mingming, Huang Jing, Shi Yue, Mprah Richard, Ding Huanhuan, Zhang Shanshan, Li Cui
Department of Physiology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, Jiangsu Province 221009, PR China; National Experimental Teaching Demonstration Center for Basic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu Province 221009, PR China.
Department of Medical Informatics Engineering, Xuzhou Medical University, Xuzhou, Jiangsu Province 221009, PR China.
Bioorg Chem. 2025 Jan;154:108089. doi: 10.1016/j.bioorg.2024.108089. Epub 2024 Dec 30.
Wenshentiaojing Decoction (WSTJD), a traditional Chinese herbal prescription, was first recorded in the "Ye Tianshi female department secret recipe for diagnosis and treatment ". It has been proven effective in treating polycystic ovary syndrome (PCOS). However, the active ingredients and molecular mechanism of WSTJD against PCOS remain unclear.
To explore the therapeutic effect and molecular mechanism of WSTJD against PCOS by using network pharmacology and mouse model.
Network pharmacology were used to predict active ingredients, potential targets, and pathways of WSTJD against PCOS. Female mice were injected subcutaneously with DHEA (6 mg/100 g body weight) daily to establish a PCOS model and administered with WSTJD and quercetin to observe its therapeutic effect. Thereafter, mouse phenotypes, indicators related to oxidative stress and ferroptosis, and hub genes were determined.
We identified 144 potential targets for WSTJD in the treatment of PCOS, which were enriched in immune-related signaling pathways such as reactive oxygen species, TNF and IL-17 signaling pathway. Thirteen hub genes were identified by proteinprotein interaction network (PPI) and algorithmic analysis, all of which were oxidative stress-related genes, and five of which, IL6, PTGS2, HIF1A, MTOR and EGFR, were ferroptosis-related genes. Further analysis revealed that quercetin was a key ingredient for WSTJD and that it had superior binding effects with the hub genes. Moreover, WSTJD and quercetin could significantly depress oxidative stress-related indicators and ferroptosis-related gene expression in PCOS mice. Finally, mouse models showed that the expression of the hub genes were consistent with the analysis results.
WSTJD and quercetin alleviated PCOS by suppressing oxidative stress and ferroptosis. Quercetin was the key ingredient for WSTJD against PCOS.
温肾调经汤(WSTJD)是一首传统中药方剂,首载于《叶天士女科秘传诊疗秘方》。已证实其对多囊卵巢综合征(PCOS)有效。然而,WSTJD治疗PCOS的活性成分和分子机制仍不清楚。
通过网络药理学和小鼠模型探讨WSTJD对PCOS的治疗作用及分子机制。
采用网络药理学预测WSTJD治疗PCOS的活性成分、潜在靶点和通路。雌性小鼠每日皮下注射脱氢表雄酮(DHEA,6mg/100g体重)建立PCOS模型,并给予WSTJD和槲皮素观察其治疗效果。此后,测定小鼠表型、氧化应激和铁死亡相关指标以及核心基因。
我们确定了WSTJD治疗PCOS的144个潜在靶点,这些靶点富集于活性氧、TNF和IL-17信号通路等免疫相关信号通路。通过蛋白质-蛋白质相互作用网络(PPI)和算法分析确定了13个核心基因,均为氧化应激相关基因,其中5个基因,即IL6、PTGS2、HIF1A、MTOR和EGFR,为铁死亡相关基因。进一步分析表明,槲皮素是WSTJD的关键成分,且与核心基因具有较强的结合作用。此外,WSTJD和槲皮素可显著降低PCOS小鼠氧化应激相关指标和铁死亡相关基因的表达。最后,小鼠模型显示核心基因的表达与分析结果一致。
WSTJD和槲皮素通过抑制氧化应激和铁死亡改善PCOS。槲皮素是WSTJD治疗PCOS的关键成分。