Cargando…

Inhibition of TLR4/MAPKs Pathway Contributes to the Protection of Salvianolic Acid A Against Lipotoxicity-Induced Myocardial Damage in Cardiomyocytes and Obese Mice

The occurrence of lipotoxicity during obesity-associated cardiomyopathy is detrimental to health. Salvianolic acid A (SAA), a natural polyphenol extract of Salvia miltiorrhiza Bunge (Danshen in China), is known to be cardioprotective. However, its clinical benefits against obesity-associated cardiom...

Descripción completa

Detalles Bibliográficos
Autores principales: Yang, Zhen, Chen, Yanli, Yan, Zhaoyuan, Xu, Tian Tian, Wu, Xiangyao, Pi, Aiwen, Liu, Qingsheng, Chai, Hui, Li, Songtao, Dou, Xiaobing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982403/
https://www.ncbi.nlm.nih.gov/pubmed/33762947
http://dx.doi.org/10.3389/fphar.2021.627123
_version_ 1783667708764618752
author Yang, Zhen
Chen, Yanli
Yan, Zhaoyuan
Xu, Tian Tian
Wu, Xiangyao
Pi, Aiwen
Liu, Qingsheng
Chai, Hui
Li, Songtao
Dou, Xiaobing
author_facet Yang, Zhen
Chen, Yanli
Yan, Zhaoyuan
Xu, Tian Tian
Wu, Xiangyao
Pi, Aiwen
Liu, Qingsheng
Chai, Hui
Li, Songtao
Dou, Xiaobing
author_sort Yang, Zhen
collection PubMed
description The occurrence of lipotoxicity during obesity-associated cardiomyopathy is detrimental to health. Salvianolic acid A (SAA), a natural polyphenol extract of Salvia miltiorrhiza Bunge (Danshen in China), is known to be cardioprotective. However, its clinical benefits against obesity-associated cardiomyocyte injuries are unclear. This study aimed at evaluating the protective effects of SAA against lipotoxicity-induced myocardial injury and its underlying mechanisms in high fat diet (HFD)-fed mice and in palmitate-treated cardiomyocyte cells (H9c2). Our analysis of aspartate aminotransferase and creatine kinase isoenzyme-MB (CM-KB) levels revealed that SAA significantly reversed HFD-induced myocardium morphological changes and improved myocardial damage. Salvianolic acid A pretreatment ameliorated palmitic acid-induced myocardial cell death and was accompanied by mitochondrial membrane potential and intracellular reactive oxygen species improvement. Analysis of the underlying mechanisms showed that SAA reversed myocardial TLR4 induction in HFD-fed mice and H9c2 cells. Palmitic acid-induced cell death was significantly reversed by CLI-95, a specific TLR4 inhibitor. TLR4 activation by LPS significantly suppressed SAA-mediated lipotoxicity protection. Additionally, SAA inhibited lipotoxicity-mediated expression of TLR4 target genes, including MyD88 and p-JNK/MAPK in HFD-fed mice and H9c2 cells. However, SAA did not exert any effect on palmitic acid-induced SIRT1 suppression and p-AMPK induction. In conclusion, our data shows that SAA protects against lipotoxicity-induced myocardial damage through a TLR4/MAPKs mediated mechanism.
format Online
Article
Text
id pubmed-7982403
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-79824032021-03-23 Inhibition of TLR4/MAPKs Pathway Contributes to the Protection of Salvianolic Acid A Against Lipotoxicity-Induced Myocardial Damage in Cardiomyocytes and Obese Mice Yang, Zhen Chen, Yanli Yan, Zhaoyuan Xu, Tian Tian Wu, Xiangyao Pi, Aiwen Liu, Qingsheng Chai, Hui Li, Songtao Dou, Xiaobing Front Pharmacol Pharmacology The occurrence of lipotoxicity during obesity-associated cardiomyopathy is detrimental to health. Salvianolic acid A (SAA), a natural polyphenol extract of Salvia miltiorrhiza Bunge (Danshen in China), is known to be cardioprotective. However, its clinical benefits against obesity-associated cardiomyocyte injuries are unclear. This study aimed at evaluating the protective effects of SAA against lipotoxicity-induced myocardial injury and its underlying mechanisms in high fat diet (HFD)-fed mice and in palmitate-treated cardiomyocyte cells (H9c2). Our analysis of aspartate aminotransferase and creatine kinase isoenzyme-MB (CM-KB) levels revealed that SAA significantly reversed HFD-induced myocardium morphological changes and improved myocardial damage. Salvianolic acid A pretreatment ameliorated palmitic acid-induced myocardial cell death and was accompanied by mitochondrial membrane potential and intracellular reactive oxygen species improvement. Analysis of the underlying mechanisms showed that SAA reversed myocardial TLR4 induction in HFD-fed mice and H9c2 cells. Palmitic acid-induced cell death was significantly reversed by CLI-95, a specific TLR4 inhibitor. TLR4 activation by LPS significantly suppressed SAA-mediated lipotoxicity protection. Additionally, SAA inhibited lipotoxicity-mediated expression of TLR4 target genes, including MyD88 and p-JNK/MAPK in HFD-fed mice and H9c2 cells. However, SAA did not exert any effect on palmitic acid-induced SIRT1 suppression and p-AMPK induction. In conclusion, our data shows that SAA protects against lipotoxicity-induced myocardial damage through a TLR4/MAPKs mediated mechanism. Frontiers Media S.A. 2021-03-08 /pmc/articles/PMC7982403/ /pubmed/33762947 http://dx.doi.org/10.3389/fphar.2021.627123 Text en Copyright © 2021 Yang, Chen, Yan, Xu, Wu, Pi, Liu, Chai, Li and Dou. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Yang, Zhen
Chen, Yanli
Yan, Zhaoyuan
Xu, Tian Tian
Wu, Xiangyao
Pi, Aiwen
Liu, Qingsheng
Chai, Hui
Li, Songtao
Dou, Xiaobing
Inhibition of TLR4/MAPKs Pathway Contributes to the Protection of Salvianolic Acid A Against Lipotoxicity-Induced Myocardial Damage in Cardiomyocytes and Obese Mice
title Inhibition of TLR4/MAPKs Pathway Contributes to the Protection of Salvianolic Acid A Against Lipotoxicity-Induced Myocardial Damage in Cardiomyocytes and Obese Mice
title_full Inhibition of TLR4/MAPKs Pathway Contributes to the Protection of Salvianolic Acid A Against Lipotoxicity-Induced Myocardial Damage in Cardiomyocytes and Obese Mice
title_fullStr Inhibition of TLR4/MAPKs Pathway Contributes to the Protection of Salvianolic Acid A Against Lipotoxicity-Induced Myocardial Damage in Cardiomyocytes and Obese Mice
title_full_unstemmed Inhibition of TLR4/MAPKs Pathway Contributes to the Protection of Salvianolic Acid A Against Lipotoxicity-Induced Myocardial Damage in Cardiomyocytes and Obese Mice
title_short Inhibition of TLR4/MAPKs Pathway Contributes to the Protection of Salvianolic Acid A Against Lipotoxicity-Induced Myocardial Damage in Cardiomyocytes and Obese Mice
title_sort inhibition of tlr4/mapks pathway contributes to the protection of salvianolic acid a against lipotoxicity-induced myocardial damage in cardiomyocytes and obese mice
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982403/
https://www.ncbi.nlm.nih.gov/pubmed/33762947
http://dx.doi.org/10.3389/fphar.2021.627123
work_keys_str_mv AT yangzhen inhibitionoftlr4mapkspathwaycontributestotheprotectionofsalvianolicacidaagainstlipotoxicityinducedmyocardialdamageincardiomyocytesandobesemice
AT chenyanli inhibitionoftlr4mapkspathwaycontributestotheprotectionofsalvianolicacidaagainstlipotoxicityinducedmyocardialdamageincardiomyocytesandobesemice
AT yanzhaoyuan inhibitionoftlr4mapkspathwaycontributestotheprotectionofsalvianolicacidaagainstlipotoxicityinducedmyocardialdamageincardiomyocytesandobesemice
AT xutiantian inhibitionoftlr4mapkspathwaycontributestotheprotectionofsalvianolicacidaagainstlipotoxicityinducedmyocardialdamageincardiomyocytesandobesemice
AT wuxiangyao inhibitionoftlr4mapkspathwaycontributestotheprotectionofsalvianolicacidaagainstlipotoxicityinducedmyocardialdamageincardiomyocytesandobesemice
AT piaiwen inhibitionoftlr4mapkspathwaycontributestotheprotectionofsalvianolicacidaagainstlipotoxicityinducedmyocardialdamageincardiomyocytesandobesemice
AT liuqingsheng inhibitionoftlr4mapkspathwaycontributestotheprotectionofsalvianolicacidaagainstlipotoxicityinducedmyocardialdamageincardiomyocytesandobesemice
AT chaihui inhibitionoftlr4mapkspathwaycontributestotheprotectionofsalvianolicacidaagainstlipotoxicityinducedmyocardialdamageincardiomyocytesandobesemice
AT lisongtao inhibitionoftlr4mapkspathwaycontributestotheprotectionofsalvianolicacidaagainstlipotoxicityinducedmyocardialdamageincardiomyocytesandobesemice
AT douxiaobing inhibitionoftlr4mapkspathwaycontributestotheprotectionofsalvianolicacidaagainstlipotoxicityinducedmyocardialdamageincardiomyocytesandobesemice