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...
Autores principales: | , , , , , , , , , |
---|---|
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 |