Synergistic Effects of Bavachinin in Combination With Either Ezetimibe or Atorvastatin on Liver Biomarkers: A Randomized Controlled Trial in Hyperlipidemic Rats With NAFLD

Seyed Amirhadi  Hosseini; Yazdan  Naderi; Seyedalireza  Mirilavasani; Frits Van  Osch; Rasoul  Samimi; Zohreh  Abdolvahabi; Hossein  Piri

doi:10.18502/acta.v63i5.20345

Seyed Amirhadi Hosseini Student Research Committee, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
Yazdan Naderi Department of Pharmacology, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
Seyedalireza Mirilavasani Health Food Innovation Management, Maastricht University, Campus Venlo, Venlo, The Netherlands
Frits Van Osch Department of Clinical Epidemiology, VieCuri Medical Centre, Venlo, The Netherlands
Rasoul Samimi Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran
Zohreh Abdolvahabi Department of Biochemistry and Genetics, Qazvin University of Medical Sciences, Qazvin, Iran
Hossein Piri Non-communicable Diseases Research Center, Research Institute for Prevention of Non-communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran

DOI: https://doi.org/10.18502/acta.v63i5.20345

Keywords: Bavachinin; Nonalcoholic fatty liver disease (NAFLD); Peroxisome proliferator-activated receptors (PPAR)

Abstract

Bavachinin, a flavonoid derived from Psoralea corylifolia, exhibits antioxidant and anti-inflammatory properties and functions as a pan-agonist of PPAR nuclear receptors. This study aimed to evaluate the individual and combined effects of bavachinin with either ezetimibe or atorvastatin on liver function markers and hepatocyte apoptosis in a rat model of diet-induced hyperlipidemia. Thirty-five male Wistar rats were randomly assigned to seven groups: normal control (NC), hyperlipidemic control (HC), bavachinin (BAV), atorvastatin (ATV), ezetimibe (EZI), ATV+BAV, and EZI+BAV. Hyperlipidemia was induced in all groups except NC. Serum levels of AST, ALT, ALP, and IL-10 were measured before and after the 4-week intervention period. Liver tissue was assessed using TUNEL staining. Wilcoxon signed-rank tests showed significant within-group reductions in AST in all intervention groups (P<0.05). ALT significantly decreased in the BAV and ATV+BAV groups. IL-10 levels significantly increased in the EZI, BAV, ATV+BAV, and EZI+BAV groups. Kruskal-Wallis ANOVA revealed significant between-group differences in AST, ALT, and IL-10 levels across all groups (P<0.05). Post hoc Mann-Whitney U tests revealed that both combination groups (ATV+BAV and EZI+BAV) showed significant reductions in AST levels compared with the HC group, and the EZI+BAV group also demonstrated a significant reduction in ALT. IL-10 levels exhibited significant improvements in both combination groups compared with BAV alone. Additionally, TUNEL staining indicated reduced hepatocyte apoptosis in both combination groups as well as in the BAV group relative to the HC group. Bavachinin, in combination with ezetimibe or atorvastatin, demonstrated hepatoprotective and anti-inflammatory effects in a rat model of fatty liver disease. These findings suggest potential therapeutic roles for bavachinin. However, further studies, including complete lipid profiling and oxidative stress markers, are needed.