Betulin prevents high fat diet-induced non-alcoholic fatty liver disease by mitigating oxidative stress and upregulating Nrf2 and SIRT1 in rats.

Autor: Farage AE; Department of Anatomy and Embryology, Faculty of Medicine, Kafrelsheikh University, Kafr El-Sheikh, Egypt., Abdo W; Department of Pathology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafr El-Sheikh, Egypt., Osman A; Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, Jordan; Department of Histology, Faculty of Medicine, Kafrelsheikh University, Kafrelsheikh, Egypt., Abdel-Kareem MA; Department of Anatomy and Embryology, Faculty of Medicine, Kafrelsheikh University, Kafr El-Sheikh, Egypt., Hakami ZH; Medical Laboratory Technology Department, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia., Alsulimani A; Medical Laboratory Technology Department, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia., Bin-Ammar A; Department of Clinical Nutrition, College of Applied Medical Sciences, University of Hail, Hail, Saudi Arabia., Alanazi AS; Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia., Alsuwayt B; Department of Pharmacy Practice, College of Pharmacy, University of Hafr Al-Batin, Hafr Al-Batin, Saudi Arabia., Alanazi MM; Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Antar SA; Department of Pharmacology and Biochemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta, Egypt; Center for Vascular and Heart Research, Fralin Biomedical Research Institute, Virginia Tech, Roanoke, VA, USA., Kamel EM; Chemistry Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt., Mahmoud AM; Department of Life Sciences, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, UK; Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt. Electronic address: a.mahmoud@mmu.ac.uk.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2023 Jun 01; Vol. 322, pp. 121688. Date of Electronic Publication: 2023 Apr 06.
DOI: 10.1016/j.lfs.2023.121688
Abstrakt: Non-alcoholic fatty liver disease (NAFLD) is a common chronic hepatic disorder characterized by hepatic lipid accumulation. This study explored the effect of betulin (BE), a terpenoid with promising antioxidant, anti-inflammatory and insulin sensitizing effects, on NAFLD induced by high fat diet (HFD). Rats received HFD and BE (15 and 30 mg/kg) for 12 weeks and blood and liver samples were collected for analyses. HFD caused hyperlipidemia, cholesterol and triglycerides accumulation in the liver, hepatocellular ballooning, fibrosis, insulin resistance (IR), lipid peroxidation (LPO), and NF-kB p65 upregulation. BE ameliorated serum and liver lipids, blood glucose and insulin, liver LPO, prevented steatosis and fibrosis, suppressed NF-kB p65 and enhanced antioxidants in HFD-fed rats. BE downregulated acetyl-CoA carboxylase (ACC1) and fatty acid synthase (FAS), and upregulated Nrf2, HO-1 and SIRT1 in the liver of HFD-fed rats. In silico investigations revealed the binding affinity of BE towards FAS, NF-kB, Keap1, HO-1 and SIRT1. In conclusion, BE attenuated HFD-induced NAFLD by ameliorating hyperlipidemia, IR, lipogenesis, liver lipid accumulation, and oxidative stress. The protective effect of BE was associated with enhanced Nrf2/HO-1 signaling and SIRT1.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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