Network pharmacology analysis and experimental verification of the antithrombotic active compounds of trichosanthis pericarpium (Gualoupi) in treating coronary heart disease

文献类型： 外文期刊

第一作者： Xia, Kai-rou

作者： Xia, Kai-rou;Zhang, Huang-qin;Shang, Er-xin;Guo, Sheng;Duan, Jin-ao;Liu, Pei;Zhang, Xiao-yu;Zhang, Huang-qin;Su, Ke-lei;Xiao, Qing-ling;Li, Wei-wen

作者机构：

关键词： Trichosanthis pericarpium; Antithrombosis ingredients; Coronary heart disease; Molecular docking

期刊名称：JOURNAL OF ETHNOPHARMACOLOGY （ 影响因子：5.4； 五年影响因子：5.3 ）

ISSN： 0378-8741

年卷期： 2024 年 329 卷

页码：

收录情况： SCI

摘要： Ethnopharmacological relevance: Trichosanthis pericarpium (TP; Gualoupi, pericarps of Trichosanthes kirilowii Maxim) has been used in traditional Chinese medicine (TCM) to reduce heat, resolve phlegm, promote Qi, and clear chest congestion. It is also an essential herbal ingredient in the "Gualou Xiebai" formula first recorded by Zhang Zhongjing (from the Eastern Han Dynasty) in the famous TCM classic "Jin-Gu & igrave;-Y`ao-L & uuml;e" for treating chest impediments. According to its traditional description, Gualou Xiebai is indicated for symptoms of chest impediments, which correspond to coronary heart diseases (CHD). Aim of the study: This study aimed to identify the antithrombotic compounds in Gualoupi for the treatment of CHD. Materials and methods: A CHD rat model was established with a combination of high-fat diet and isoproterenol hydrochloride (ISO) administration via subcutaneous multi-point injection in the back of the neck. This model was used to evaluate the antithrombotic effect of two mainstream cultivars of TP ("HaiShi GuaLou" and "WanLou") by analyzing the main components and their effects. Network pharmacology, molecular dockingbased studies, and a zebrafish (Danio rerio) thrombosis model induced by phenylhydrazine was used to validate the antithrombosis components of TP. Results: TP significantly reduced the body weight of the CHD rats, improved myocardial ischemia, and reduced collagen deposition and fibrosis around the infarcted tissue. It reduced thrombosis in a dose-dependent manner and significantly reduced inflammation and oxidative stress damage. Cynaroside, isoquercitrin, rutin, citrulline, and arginine were identified as candidate active TP compounds with antithrombotic effects. The key potential targets of TP in thrombosis treatment were initially identified by molecular docking-based analysis, which showed that the candidate active compounds have a strong binding affinity to the potential targets (protein kinase C alpha type [PKC alpha], protein kinase C beta type [PKC beta], von Willebrand factor [vWF], and prostaglandinendoperoxide synthase 1 [PTGS1], fibrinogen alpha [Fga], fibrinogen beta [Fgb], fibrinogen gamma [Fgg], coagulation factor II [F2], and coagulation factor VII [F7]). In addition, the candidate active compounds reduced thrombosis, improved oxidative stress damage, and down-regulated the expression of thrombosis-related genes (PKC alpha, PKC beta, vWF, PTGS1, Fga, Fgb, Fgg, F2, and F7) in the zebrafish model. Conclusion: Cynaroside, isoquercitrin, rutin, citrulline, and arginine were identified as the active antithrombotic compounds of TP used to treat CHD. Mechanistically, the active compounds were found to be involved in oxidative stress injury, platelet activation pathway, and complement and coagulation cascade pathways.

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