Regulatory effects of the combination of berberine and ginsenoside Rb1 on high-fat diet-induced nonalcoholic fatty liver disease via AMPK pathway and improved pharmacokinetics

摘要

Abstract Objective: We evaluated the protective effects of berberine (BBR) combined with ginsenoside Rb1 (G-Rb1) on high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) in rats and futher investigated the underlying mechanisms. Methods: Rats were fed an HFD for 6 weeks and then randomly divided into four groups and treated with BBR (50 mg/kg), G-Rb1 (100 mg/kg), BBR (50 mg/kg)+G-Rb1 (100 mg/kg), or fenofibrate (40 mg/kg). Histological examination of liver tissue was performed. In human hepatocellular carcinoma cells HepG2, protein expression of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase was detected by western blotting, and the mRNA expression of carnitine palmitoyl transferase 1 and 3-hydroxy-3-methyl glutaryl coenzyme A reductase was detected by quantitative PCR. Pharmacokinetic assessments included analysis of bioavailability of BBR and G-Rb1 in vivo and G-Rb1 metabolism by intestinal bacteria in vitro. Results: Compared to the single-use group, BBR combined with G-Rb1 significantly ameliorated hepatic fat accumulation in HFD-induced obese rats, as demonstrated by reduced hepatic triglyceride content, and histological evaluation of liver sections. Activation of hepatic AMPK and phosphorylation of acetyl-CoA carboxylase were significantly elevated in hepatocytes treated with both BBR and G-Rb1. Consistent with the activation of AMPK, the mRNA expression of carnitine palmitoyl transferase 1 was stimulated, while the mRNA expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase was suppressed. Pharmacokinetic analysis revealed that BBR increased the bioavailability of G-Rb1 in Sprague-Dawley rats. Additionally, BBR prevented degradation of G-Rb1 in fecal solution in vitro. Conclusion: BBR combined with G-Rb1 improved NAFLD through the AMPK signaling pathway, and BBR enhanced G-Rb1 bioavailability via promoting the intestinal absorption of G-Rb1. This combination may be a useful therapeutic agent for NAFLD.