Limonin inhibits apoptosis, promotes autophagy and improves non-alcoholic fatty liver disease by promoting oxidative metabolism of fatty acids through PPARα
10.16438/j.0513-4870.2023-0534
- VernacularTitle:柠檬苦素抑制凋亡、促进自噬并通过PPARα促进脂肪酸氧化代谢改善非酒精性脂肪性肝病
- Author:
Yang ZHA
1
;
Feng ZHANG
1
;
Jie ZHOU
1
;
Shuang ZHANG
1
;
Ya-jun DUAN
2
Author Information
1. School of Food and Biological Engineering, Hefei University of Technology, Hefei 230601, China
2. The First Affiliated Hospital of USTC (Anhui Provincial Hospital), Hefei 230022, China
- Publication Type:Research Article
- Keywords:
nonalcoholic fatty liver;
limonin;
peroxisome proliferator activates receptor alpha;
oxidative metabolism;
apoptosis;
autophagy
- From:
Acta Pharmaceutica Sinica
2023;58(8):2402-2414
- CountryChina
- Language:Chinese
-
Abstract:
Non-alcoholic fatty liver disease (NAFLD) is a very common chronic liver disease in clinic, which can further develop into liver fibrosis, cirrhosis, eventually hepatocellular carcinoma and liver failure. Limonin is a natural triterpenoid compound containing furan rings. Previous studies have found that limonin has good anti-inflammatory, analgesic and liver protective functions. However, the mechanism of action of limonin on NAFLD has not been clarified. Based on the background, C57BL/6J male mice were fed with high fat diet (HFD) to establish NAFLD model (the experiment was approved by the Animal Ethics Committee of Hefei University of Technology, the approval number is HFUT20220429001), and limonin was added to the mice for administration by intragastric administration (i.g.). The results showed that HFD can induce typical NAFLD phenotypes, including impaired liver function, increased fat accumulation, and increased serum aspartate amino transferase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) levels in mice. Mice were treated with limonin (50 and 100 mg·kg-1) for 10 weeks, and it was found that limonin could restore dyslipidemia and improve fat accumulation in liver cells of mice. In addition, we conducted in vitro experiments with human hepatoma cell line HepG2 cells, and found that limonin can promote the expression of oxidative metabolism and autophagy related genes and inhibit apoptosis in HepG2 cells. Mechanistically, limonin improves high-fat food-induced NAFLD by promoting the expression of oxidative metabolism genes transcriptional coactivator of peroxisome proliferator activating receptor γ (PPARγ) (PGC1α) and carnitine palmitoyl transferase 1 alpha (CPT1α) through peroxisome proliferator activates receptor alpha (PPARα). These results indicate that limonin can inhibit apoptosis, promote autophagy and improve NAFLD by promoting oxidative metabolism of fatty acids through PPARα.
