Oridonin interferes with simple steatosis of liver cells by regulating autophagy
Autor: | Dianlei Liu, Rui Wu, Shourong Liu, Chuntao Liu, Jianhong Jin, Xiaoqing Fu, Boning Cheng, Tingting Shi |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
AMP-Activated Protein Kinases Biology Models Biological 03 medical and health sciences 0302 clinical medicine Cyclin-dependent kinase Lipid droplet Autophagy medicine Humans Protein kinase A Protein kinase B Liver cell Fatty Acids AMPK Cell Biology General Medicine medicine.disease Molecular biology Fatty Liver 030104 developmental biology Liver 030220 oncology & carcinogenesis Hepatocytes biology.protein Steatosis Diterpenes Kaurane Proto-Oncogene Proteins c-akt Signal Transduction Developmental Biology |
Zdroj: | Tissue and Cell. 72:101532 |
ISSN: | 0040-8166 |
DOI: | 10.1016/j.tice.2021.101532 |
Popis: | Oridonin has significant liver-protective effects, but its effect on liver steatosis has not been reported. We investigated the effects of oridonin on liver steatosis by cell cultures. The optimal experimental concentration of oridonin was determined through cytotoxicity experiments. A simple steatosis liver cell model was induced using free fatty acids (FFA). After adding oridonin to the FFA-induced cell model for 24 h, the lipid droplets and triglyceride (TG) content in the cells were measured by Oil Red O staining and TG kits. The expressions of autophagy-related markers (cyclin dependent kinases inhibitor 1a (p21), Beclin-1, microtubule-associated protein light chain 3 (LC3)-I and LC3-II, protein kinase B (AKT), phosphorylated-AKT (p-AKT), AMP-activated protein kinase (AMPK), and phosphorylated-AMPK (p-AMPK)) were detected by Western blot. Based on the results, the cell model was further treated by autophagy inhibitor 3-methyladenine (3-MA) to determine the degree of steatosis and the expressions of autophagy-related factors. Oridonin at a concentration higher than 10 μmol/L caused cytotoxicity to the cells. Adding 10 μmol/L oridonin to the FFA-induced cell model effectively reduced lipid droplets and TG content in the cells. Oridonin up-regulated p21, Beclin-1 and LC3-II expressions, but down-regulated those of p62 and LC3-I. Also, oridonin increased the ratios of LC3-II/LC3-I and p-AMPK/AMPK, but reduced that of p-AKT/AKT. With the addition of 3-MA, the effect of oridonin on reducing steatosis was partially reversed, and the autophagy was inhibited. This study found that oridonin can activate autophagy, thereby preventing simple steatosis of liver cells. |
Databáze: | OpenAIRE |
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