Thymoquinone attenuates hepatic lipid accumulation by inducing autophagy via AMPK/mTOR/ULK1-dependent pathway in nonalcoholic fatty liver disease.
Phytother Res
; 37(3): 781-797, 2023 Mar.
Article
in En
| MEDLINE
| ID: mdl-36479746
ABSTRACT
Thymoquinone (TQ) has been proved to exert wide-ranging pharmacological activities, with anti-inflammatory, antioxidant, anticonvulsant, antimicrobial, anti-tumor, and antidiabetic properties. In this study, we investigated the beneficial effects of TQ on a high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) in C57BL/6 N mice in vivo and free fatty acid (FFA)-induced human hepatocellular carcinoma HepG2 cells in vitro. Further, the underlying mechanisms of TQ to promote hepatic autophagy were also discovered. Data showed that TQ caused (p < 0.01) body weight reduction, improved glucose homeostasis, alleviated hepatosteatosis, and decreased hepatic lipid accumulation related to the induction of autophagy in HFD-fed mice. In vitro, TQ obviously increased (p < 0.01) autophagic flux in FFA-induced HepG2 cells and consequently reduced the lipid accumulation in combination with activation of AMPK/mTOR/ULK1 signaling pathways. Moreover, pharmacological inhibition of the AMPK pathway by addition with AMPK inhibitor Compound C (CC) or silence of ULK1 by transfection with siRNA(ULK1) into HepG2 cells reversed these beneficial effects of TQ on triggering hepatic autophagy and reducing lipid accumulation (p < 0.01). Taken together, these results suggested that TQ alleviated hepatic lipid accumulation by triggering autophagy through the AMPK/mTOR/ULK1-dependent signaling pathway. Our study supports a potential role for TQ in ameliorating NAFLD.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Non-alcoholic Fatty Liver Disease
Limits:
Animals
/
Humans
Language:
En
Journal:
Phytother Res
Year:
2023
Document type:
Article