Plasma metabolomic analysis reveals the therapeutic effects of Jiashen tablets on heart failure

BackgroundHeart failure is a chronic progressive condition that significantly affects the quality of life of patients with high hospitalization and mortality rates. Jiashen tablets (JST), a Chinese herbal formula, have been reported to be an effective treatment against heart failure, however the und...

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Main Authors: Xinglong Miao, Jiaping Chen, Yangyan Su, Jiayi Luo, Yi He, Jiang Ma, Xin He
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-12-01
Series:Frontiers in Cardiovascular Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcvm.2022.1047322/full
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author Xinglong Miao
Jiaping Chen
Yangyan Su
Jiayi Luo
Yi He
Jiang Ma
Xin He
Xin He
author_facet Xinglong Miao
Jiaping Chen
Yangyan Su
Jiayi Luo
Yi He
Jiang Ma
Xin He
Xin He
author_sort Xinglong Miao
collection DOAJ
description BackgroundHeart failure is a chronic progressive condition that significantly affects the quality of life of patients with high hospitalization and mortality rates. Jiashen tablets (JST), a Chinese herbal formula, have been reported to be an effective treatment against heart failure, however the underlying mechanisms remain obscure. This study was designed to determine the effect of JST on the treatment of heart failure and delineate the underlying mechanisms by an untargeted metabolomics approach.Materials and methodsThe chronic heart failure model was established by the permanent ligation of the left anterior descending coronary artery in rats. The cardiac functions of rats, including left ventricular ejection fraction (LVEF) and fractional shortening (LVFS), left ventricular internal diameter end diastole (LVIDd) and end systole (LVIDs), and interventricular septum thickness in diastole (IVSd) and in systole (IVSs), were measured by echocardiography. Biochemical analysis and histopathological examination were also performed to evaluate therapeutic effects of JST for treating heart failure. UHPLC-QTOF-MS/MS coupled with multivariate statistical analyses were applied for plasma metabolic profiling to identify biomarkers and potential mechanisms of JST in the treatment of heart failure.ResultsJiashen tablets could improve the cardiac function of heart failure rats and thus ameliorate heart failure via enhancing rat LVEF and LVFS and decreasing LVIDd, LVIDs, IVSd, and IVSs. Results of biochemical analysis and histopathological examination revealed that JST could reduce the serum lactate dehydrogenase (LDH) activity and the level of NT-pro BNP, markers of heart failure and myocardial damage, and inhibit myocardial fibrosis. Furthermore, in metabolomics analysis, a total of 210 metabolites with significant differences were identified between heart failure rats and normal rats, among which 29 metabolites were significantly restored after JST treatment. These metabolites were primarily involved in tryptophan metabolism, branched-chain amino acid metabolism, fatty acids β-oxidation, and glycerophospholipid metabolism.ConclusionThe present study illustrated the therapeutic effect of JST for the treatment of heart failure and delineated the underlying mechanisms mainly relating to the regulation of amino acid metabolism and lipid metabolism in heart failure rats.
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spelling doaj.art-3554214480cc4ad8ab71de71e9b9ab4a2022-12-22T04:21:28ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-12-01910.3389/fcvm.2022.10473221047322Plasma metabolomic analysis reveals the therapeutic effects of Jiashen tablets on heart failureXinglong Miao0Jiaping Chen1Yangyan Su2Jiayi Luo3Yi He4Jiang Ma5Xin He6Xin He7School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaSchool of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, ChinaSchool of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, ChinaSchool of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, ChinaState Key Laboratory of Core Technology in Innovative Chinese Medicine, Tasly Pharmaceutical Group Co., Ltd., Tianjin, ChinaSchool of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, ChinaSchool of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaSchool of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, ChinaBackgroundHeart failure is a chronic progressive condition that significantly affects the quality of life of patients with high hospitalization and mortality rates. Jiashen tablets (JST), a Chinese herbal formula, have been reported to be an effective treatment against heart failure, however the underlying mechanisms remain obscure. This study was designed to determine the effect of JST on the treatment of heart failure and delineate the underlying mechanisms by an untargeted metabolomics approach.Materials and methodsThe chronic heart failure model was established by the permanent ligation of the left anterior descending coronary artery in rats. The cardiac functions of rats, including left ventricular ejection fraction (LVEF) and fractional shortening (LVFS), left ventricular internal diameter end diastole (LVIDd) and end systole (LVIDs), and interventricular septum thickness in diastole (IVSd) and in systole (IVSs), were measured by echocardiography. Biochemical analysis and histopathological examination were also performed to evaluate therapeutic effects of JST for treating heart failure. UHPLC-QTOF-MS/MS coupled with multivariate statistical analyses were applied for plasma metabolic profiling to identify biomarkers and potential mechanisms of JST in the treatment of heart failure.ResultsJiashen tablets could improve the cardiac function of heart failure rats and thus ameliorate heart failure via enhancing rat LVEF and LVFS and decreasing LVIDd, LVIDs, IVSd, and IVSs. Results of biochemical analysis and histopathological examination revealed that JST could reduce the serum lactate dehydrogenase (LDH) activity and the level of NT-pro BNP, markers of heart failure and myocardial damage, and inhibit myocardial fibrosis. Furthermore, in metabolomics analysis, a total of 210 metabolites with significant differences were identified between heart failure rats and normal rats, among which 29 metabolites were significantly restored after JST treatment. These metabolites were primarily involved in tryptophan metabolism, branched-chain amino acid metabolism, fatty acids β-oxidation, and glycerophospholipid metabolism.ConclusionThe present study illustrated the therapeutic effect of JST for the treatment of heart failure and delineated the underlying mechanisms mainly relating to the regulation of amino acid metabolism and lipid metabolism in heart failure rats.https://www.frontiersin.org/articles/10.3389/fcvm.2022.1047322/fullheart failureJiashen tabletsLAD ligationcardiac functionplasma metabolomics
spellingShingle Xinglong Miao
Jiaping Chen
Yangyan Su
Jiayi Luo
Yi He
Jiang Ma
Xin He
Xin He
Plasma metabolomic analysis reveals the therapeutic effects of Jiashen tablets on heart failure
Frontiers in Cardiovascular Medicine
heart failure
Jiashen tablets
LAD ligation
cardiac function
plasma metabolomics
title Plasma metabolomic analysis reveals the therapeutic effects of Jiashen tablets on heart failure
title_full Plasma metabolomic analysis reveals the therapeutic effects of Jiashen tablets on heart failure
title_fullStr Plasma metabolomic analysis reveals the therapeutic effects of Jiashen tablets on heart failure
title_full_unstemmed Plasma metabolomic analysis reveals the therapeutic effects of Jiashen tablets on heart failure
title_short Plasma metabolomic analysis reveals the therapeutic effects of Jiashen tablets on heart failure
title_sort plasma metabolomic analysis reveals the therapeutic effects of jiashen tablets on heart failure
topic heart failure
Jiashen tablets
LAD ligation
cardiac function
plasma metabolomics
url https://www.frontiersin.org/articles/10.3389/fcvm.2022.1047322/full
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