Salvianolic acid A improves palmitie acid-induced lipotoxicity in cardiomyocyte via inhibiting TLR4/JNK MAPK
10.12092/j.issn.1009-2501.2021.02.001
- Author:
Tiantian XU
1
;
Xiangyao WU
1
;
Aiwen PI
1
;
Hui CHAI
1
;
Xiaobing DOU
1
;
Hui CHAI
2
;
Xiaobing DOU
2
;
Bin ZHANG
3
;
Bangcai WANG
3
;
Linwensi ZHU
4
Author Information
1. School of Life Science, Zhejiang Chinese Medical University
2. Institute of Molecular Medicine, Zhejiang Chinese Medical University
3. Department of Gastroenterology, Ningbo Traditional Chinese Medicine Hospital
4. Department of Gastroenterology, The First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine
- Publication Type:Journal Article
- Keywords:
Cardiomyocyte;
Lipotoxicity;
Palmitie acid;
Salvianolic acid A;
Toll-like receptor 4
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2021;26(2):121-128
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To reveal the ameliorative effect of salvianolic acid A on palmitie acid-induced lipotoxicity in H9C2 cells and to explore its potential molecular mechanisms preliminarily. METHODS: H9C2 cell were induced by palmitie acid to establish a lipotoxicity model, while salvianolic acid A was added prior to palmitie acid treatment. Lactate dehydrogenase (LDH) was employed to detect cell damage. Cell counting Kit-8 was used to detect cell viability. The changes of mitochondrial membrane potential in cardiomyocyte were observed by rhodamine 123 staining. The molecular mechanisms of the ameliorative effect of salvianolic acid A was analyzed by Western Blotting. RESULTS: Palmitie acid at a concentration of 400 μmol/L significantly caused lipotoxicity damage to H9C2 cells (P<0.05). There was no cytotoxic effect of different concentrations of salvianolic acid A (10, 20, 40, 80 μmol/L) treatment on H9C2 cells (P>0.05). Salvianolic acid A intervention significantly improved lipotoxicity-induced cell death and reduction of cell mitochondrial membrane potential (P<0.05). The activation of toll-like receptor 4 (TLR4) significantly enhanced lipotoxicity-induced cell damage (P<0.05), while inhibition of TLR4 significantly reduced palmitie acid-induced lipotoxicity (P<0.05). In addition, salvianolic acid A effectively inhibited the upregulation of TLR4 and the downstream c-Jun N-terminal kinase (JNK MAPK) of TLR4 by palmitie acid treatment (P<0.05). CONCLUSION: Salvianolic acid A effectively improves lipotoxicity-induced cardiomyocyte damage. The inhibition of p38 signaling pathway is potentially involved in its protective effect. The protective effect may be related to the inhibition of TLR4/JNK MAPK signaling pathway, providing a potential molecular target for the prevention and treatment of lipotoxic cardiomyopathy.
