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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.627123/full |
| _version_ | 1818849303777509376 |
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| author | Zhen Yang Zhen Yang Zhen Yang Yanli Chen Yanli Chen Zhaoyuan Yan Tian Tian Xu Xiangyao Wu Aiwen Pi Qingsheng Liu Hui Chai Hui Chai Songtao Li Songtao Li Xiaobing Dou Xiaobing Dou |
| author_facet | Zhen Yang Zhen Yang Zhen Yang Yanli Chen Yanli Chen Zhaoyuan Yan Tian Tian Xu Xiangyao Wu Aiwen Pi Qingsheng Liu Hui Chai Hui Chai Songtao Li Songtao Li Xiaobing Dou Xiaobing Dou |
| author_sort | Zhen Yang |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T06:31:06Z |
| format | Article |
| id | doaj.art-bdfd08f061ee445f9017a8976aa05f4a |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-19T06:31:06Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-bdfd08f061ee445f9017a8976aa05f4a2022-12-21T20:32:24ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-03-011210.3389/fphar.2021.627123627123Inhibition of TLR4/MAPKs Pathway Contributes to the Protection of Salvianolic Acid A Against Lipotoxicity-Induced Myocardial Damage in Cardiomyocytes and Obese MiceZhen Yang0Zhen Yang1Zhen Yang2Yanli Chen3Yanli Chen4Zhaoyuan Yan5Tian Tian Xu6Xiangyao Wu7Aiwen Pi8Qingsheng Liu9Hui Chai10Hui Chai11Songtao Li12Songtao Li13Xiaobing Dou14Xiaobing Dou15College of Basic Medicine and Public Health, Zhejiang Chinese Medical University, Hangzhou, ChinaCollege of Life Science, Zhejiang Chinese Medical University, Hangzhou, ChinaMolecular Medicine Institute, Zhejiang Chinese Medical University, Hangzhou, ChinaCollege of Basic Medicine and Public Health, Zhejiang Chinese Medical University, Hangzhou, ChinaCollege of Life Science, Zhejiang Chinese Medical University, Hangzhou, ChinaCollege of Life Science, Zhejiang Chinese Medical University, Hangzhou, ChinaCollege of Life Science, Zhejiang Chinese Medical University, Hangzhou, ChinaCollege of Life Science, Zhejiang Chinese Medical University, Hangzhou, ChinaCollege of Life Science, Zhejiang Chinese Medical University, Hangzhou, ChinaHangzhou Hospital of Traditional Chinese Medicine, Guangxing Hospital Affiliated to Zhejiang University of Traditional Chinese Medicine, Hangzhou, ChinaCollege of Life Science, Zhejiang Chinese Medical University, Hangzhou, ChinaMolecular Medicine Institute, Zhejiang Chinese Medical University, Hangzhou, ChinaCollege of Basic Medicine and Public Health, Zhejiang Chinese Medical University, Hangzhou, ChinaMolecular Medicine Institute, Zhejiang Chinese Medical University, Hangzhou, ChinaCollege of Life Science, Zhejiang Chinese Medical University, Hangzhou, ChinaMolecular Medicine Institute, Zhejiang Chinese Medical University, Hangzhou, ChinaThe 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.https://www.frontiersin.org/articles/10.3389/fphar.2021.627123/fullsalvianolic acid Alipotoxicitymyocardial injuryTLR4MAPKs |
| spellingShingle | Zhen Yang Zhen Yang Zhen Yang Yanli Chen Yanli Chen Zhaoyuan Yan Tian Tian Xu Xiangyao Wu Aiwen Pi Qingsheng Liu Hui Chai Hui Chai Songtao Li Songtao Li Xiaobing Dou Xiaobing Dou Inhibition of TLR4/MAPKs Pathway Contributes to the Protection of Salvianolic Acid A Against Lipotoxicity-Induced Myocardial Damage in Cardiomyocytes and Obese Mice Frontiers in Pharmacology salvianolic acid A lipotoxicity myocardial injury TLR4 MAPKs |
| 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 | salvianolic acid A lipotoxicity myocardial injury TLR4 MAPKs |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.627123/full |
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