The mechanism of Renshen-Fuzi herb pair for treating heart failure-Integrating a cardiovascular pharmacological assessment with serum metabolomics

被引：6

作者：

Chen, Xiaofei ^{[1
,2
]}

Chen, Yulong ^{[3
]}

Xie, Shiyang ^{[2
]}

Wang, Xiaoyan ^{[2
]}

Wu, Yali ^{[2
]}

Zhang, Hui ^{[2
]}

Zhao, Ya ^{[2
]}

Jia, Jinhao ^{[3
]}

Wang, Bin ^{[3
]}

Li, Weixia ^{[2
]}

Tang, Jinfa ^{[2
]}

Xiao, Xiaohe ^{[4
]}

机构：

[1] Chengdu Univ Chinese Med, Coll Med, Chengdu, Peoples R China

[2] Henan Univ Chinese Med, Henan Prov Engn Lab Clin Evaluat Technol Chinese M, Henan Prov Engn Res Ctr Clin Applicat Evaluat & Tr, Affiliated Hosp 1, Zhengzhou, Peoples R China

[3] Henan Univ Chinese Med, Coll Med, Zhengzhou, Peoples R China

[4] Chinese Peoples Liberat Army Gen Hosp, Dept Hepatol, Med Ctr 5, Beijing, Peoples R China

来源：

FRONTIERS IN PHARMACOLOGY | 2022年 / 13卷

关键词：

Panax ginseng CAMey; Aconitum carmichaeli Debeaux; heart failure; combination mechanisms; cardiovascular pharmacological; serum metabolomics; SOLUBLE EPOXIDE HYDROLASE; IMPROVES CARDIAC-FUNCTION; MONOAMINE-OXIDASE; MYOCARDIAL-INFARCTION; COMBINATION THERAPY; PURINE METABOLISM; GINSENOSIDE RB1; INHIBITION; ALKALOIDS; DISCOVERY;

D O I：

10.3389/fphar.2022.995796

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Background:Renshen-Fuzi herb pair (RS-FZ) is often used in the clinical treatment of heart failure (HF) and has a remarkable therapeutic effect. However, the mechanism of RS-FZ for treating HF remains unclear. In our study, we explored the mechanism of RS-FZ for treating HF. Methods:Evaluation of RS-FZ efficacy by cardiovascular pharmacology. Moreover, Global metabolomics profiling of the serum was detected by UPLC-QTOF/MS. Multivariate statistics analyzed the specific serum metabolites and corresponding metabolic pathways. Combining serum metabolomics with network pharmacology, animal experiments screened and validated the critical targets of RS-FZ intervention in HF. Results:RS-FZ significantly ameliorated myocardial fibrosis, enhanced cardiac function, and reduced the serum HF marker (brain natriuretic peptide) level in rats with HF. Through topological analysis of the "Metabolite-Target-Component " interaction network, we found that 79 compounds of RS-FZ directly regulated the downstream specific serum metabolites by acting on four critical target proteins (CYP2D6, EPHX2, MAOB, and ENPP2). The immunohistochemistry results showed that RS-FZ observably improved the expression of CYP2D6 and ENPP2 proteins while decreasing the expression of EPHX2 and MAOB proteins dramatically. Conclusion:The integrated cardiovascular pharmacological assessment with serum metabolomics revealed that RS-FZ plays a crucial role in the treatment of HF by intervening in CYP2D6, EPHX2, MAOB, and ENPP2 target proteins. It provides a theoretical basis for RS-FZ for treating HF.

引用

页数：14