文献类型： 外文期刊

作者： Zhang, Xiao-yu ¹ ; Xia, Kai-rou ² ; Wang, Ya-ni ¹ ; Liu, Pei ² ; Shang, Er-xin ² ; Liu, Cong-yan ¹ ; Liu, Yu-Ping ¹ ; Qu, Ding ¹ ; Li, Wei-wen ³ ; Duan, Jin-ao ² ; Chen, Yan ¹ ; Zhang, Huang-qin ¹ ;

作者机构： 1.Nanjing Univ Chinese Med, Affiliated Hosp Integrated Tradit Chinese & Wester, Clin Med Coll 3, Nanjing 210028, Peoples R China

2.Nanjing Univ Chinese Med, Jiangsu Collaborat Innovat Ctr Chinese Med Resourc, Natl & Local Collaborat Engn Ctr Chinese Med Resou, Jiangsu Key Lab High Technol Res TCM Formulae, Nanjing 210023, Peoples R China

3.Anhui Acad Agr Sci, Inst Hort, Hefei 230031, Peoples R China

关键词： Trichosanthis Pericarpium; Coronary heart disease; Plasma pharmacochemistry; Network pharmacology; Multi-pathway mechanism

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 325 卷

页码：

收录情况： SCI

摘要： Ethnopharmacological relevance: Coronary heart disease (CHD) is a chronic disease that seriously threatens people's health and even their lives. Currently, there is no ideal drug without side effects for the treatment of CHD. Trichosanthis Pericarpium (TP) has been used for several years in the treatment of diseases associated with CHD. However, there is still a need for systematic research to unravel the pharmacodynamic substances and possible mechanism of TP in the treatment of coronary heart. Aim of the study: The purpose of current study was to explore the pharmacodynamic substances and potential mechanisms of TP in the treatment of CHD via integrating network pharmacology with plasma pharmacochemistry and experimental validation. Materials and methods: The effect of TP intervention in CHD was firstly assessed on high-fat diet combined with isoprenaline-induced CHD rats and H2O2-induced H9c2 cells, respectively. Then, the LC-MS was utilized to identify the absorbed components of TP in the plasma of CHD rats, and this was used to develop a network pharmacology prediction to obtain the possible active components and mechanisms of action. Molecular docking and immunohistochemistry were used to explore the interaction between TP and key targets. Subsequently, the efficacy of the active ingredients was investigated by in vitro cellular experiments, and their metabolic pathways in CHD rats were further analyzed. Results: The effects of TP on amelioration of CHD were verified by in vivo and in vitro experiments. Plasma pharmacochemistry and network pharmacology screened six active components in plasma including apigenin, phenylalanine, quercetin, linoleic acid, luteolin, and tangeretin. The interaction of these compounds with potential key targets AKT1, IL-1 beta, IL -6, TNF-alpha and VEGFA were preliminarily verified by molecular docking. And immunohistochemical results showed that TP reduced the expression of AKT1, IL-1 beta, IL -6, TNF-alpha and VEGFA in CHD rat hearts. Then cellular experiments confirmed that apigenin, phenylalanine, quercetin, linoleic acid, luteolin, and tangeretin were able to reduce the ROS level in H2O2-induced HUVEC cells and promote the