Catalpol inhibits cell apoptosis through alleviating endoplasmic reticulum stress in nonalcoholic fatty liver disease
10.16438/j.0513-4870.2020-1986
- VernacularTitle:梓醇缓解内质网应激抑制非酒精性脂肪肝细胞凋亡
- Author:
Xiang TIAN
1
,
2
;
Qi XIONG
1
;
Kai YUE
1
;
Mei ZHOU
1
;
Kuan LIN
1
;
Bao-miao MA
1
;
Yong CHEN
3
;
Qin RU
1
Author Information
1. Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China
2. Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, National and Local Joint Engineering Research Center of High-throughput Drug Screening Technology, Hubei University, Wuhan 430062, China
3. Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, National and Local Joint Engineering Research Center of High-throughput Drug Screening Technology, Hubei University, Wuhan 430062, China
- Publication Type:Research Article
- Keywords:
nonalcoholic fatty liver disease;
catalpol;
high fat diet;
palmitate;
endoplasmic reticulum;
hepatocytes apoptosis
- From:
Acta Pharmaceutica Sinica
2021;56(6):1634-1643
- CountryChina
- Language:Chinese
-
Abstract:
This study was designed to explore the protective effect and underlying mechanism of catalpol on hepatocyte apoptosis in nonalcoholic fatty liver disease (NAFLD). High fat diet (HFD) was used to establish NAFLD model in the in vivo experiment, and the procedures of the experiments and animal care protocol were approved by the Animal Care and Use Committee of Jianghan University. Human liver cancer cell line HepG2 was treated with palmitate (PA) to establish a lipid toxicity model in the in vitro experiments. The results showed that catalpol significantly decreased the contents of serum total glyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), and aspartate transaminase (AST) in HFD-fed mice. Results of TUNEL staining and flow cytometry analyses revealed that catalpol significantly inhibited hepatocytes apoptosis in HFD-fed mice and PA-treated HepG2 cells. Moreover, catalpol treatment significantly reduced the endoplasmic reticulum stress-related protein expression levels of binding immunoglobulin protein (BiP), phosphorylated PKR-like endoplasmic reticulum kinase (p-PERK), inositol-requiring kinase 1α (IRE1α), and transcriptional factor activating transcription factor 6 (ATF6), and apoptosis-related protein expression levels of C/EBP homology protein (CHOP), phosphorylated c-Jun N-terminal kinase (p-JNK), and cleaved cysteinyl aspartate specific proteinases (caspases)-12, -9, and -3 in HFD-fed mice and PA-treated HepG2 cells. Furthermore, endoplasmic reticulum stress agonist tunicamycin (TM) significantly reversed the inhibitory effect of catalpol on protein expression levels of BiP, p-PERK, IRE1α, and ATF6, subsequently the inhibitory effect of catalpol on expression levels of CHOP, p-JNK, Bcl-2, Bax, and cleaved caspases (-12, -9, and -3) was also attenuated in PA-treated HepG2 cells. Taken together, these findings demonstrated that catalpol could inhibit hepatocytes apoptosis and had a significant protective effect on liver injury, and its mechanism might be related to the relief of endoplasmic reticulum stress.
