Objective： We evaluated the protective effects of berberine （BBR） combined with ginsenoside Rb1 （G-Rb1） on high-fatdiet （HFD）-induced nonalcoholic fatty liver disease （NAFLD） in rats and futher investigated t...Objective： We evaluated the protective effects of berberine （BBR） combined with ginsenoside Rb1 （G-Rb1） on high-fatdiet （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 （50mg/kg）, G-Rb1 （100 mg/kg）, BBR （50 mg/kg） ＋ G-Rb1 （100 mg/kg）, or fenofibrate （40 mg/kg）. Histological examinationof liver tissue was performed. In human hepatocellular carcinoma cells HepG2, protein expression of AMP-activatedprotein kinase （AMPK） and acetyl-CoA carboxylase was detected by western blotting, and the mRNA expression ofcarnitine palmitoyl transferase 1 and 3-hydroxy-3-methyl glutaryl coenzyme A reductase was detected by quantitativePCR. Pharmacokinetic assessments included analysis of bioavailability of BBR and G-Rb1 in vivo and G-Rb1 metabolismby intestinal bacteria in vitro. Results： Compared to the single-use group, BBR combined with G-Rb1 significantlyameliorated hepatic fat accumulation in HFD-induced obese rats, as demonstrated by reduced hepatic triglyceridecontent, and histological evaluation of liver sections. Activation of hepatic AMPK and phosphorylation of acetyl-CoAcarboxylase were significantly elevated in hepatocytes treated with both BBR and G-Rb1. Consistent with the activationof AMPK, the mRNA expression of carnitine palmitoyl transferase 1 was stimulated, while the mRNA expression of3-hydroxy-3-methyl glutaryl coenzyme A reductase was suppressed. Pharmacokinetic analysis revealed that BBRincreased the bioavailability of G-Rb1 in Sprague-Dawley rats. Additionally, BBR prevented degradation of G-Rb1 infecal 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 auseful therapeutic agent for NAFLD.展开更多
文摘Objective： We evaluated the protective effects of berberine （BBR） combined with ginsenoside Rb1 （G-Rb1） on high-fatdiet （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 （50mg/kg）, G-Rb1 （100 mg/kg）, BBR （50 mg/kg） ＋ G-Rb1 （100 mg/kg）, or fenofibrate （40 mg/kg）. Histological examinationof liver tissue was performed. In human hepatocellular carcinoma cells HepG2, protein expression of AMP-activatedprotein kinase （AMPK） and acetyl-CoA carboxylase was detected by western blotting, and the mRNA expression ofcarnitine palmitoyl transferase 1 and 3-hydroxy-3-methyl glutaryl coenzyme A reductase was detected by quantitativePCR. Pharmacokinetic assessments included analysis of bioavailability of BBR and G-Rb1 in vivo and G-Rb1 metabolismby intestinal bacteria in vitro. Results： Compared to the single-use group, BBR combined with G-Rb1 significantlyameliorated hepatic fat accumulation in HFD-induced obese rats, as demonstrated by reduced hepatic triglyceridecontent, and histological evaluation of liver sections. Activation of hepatic AMPK and phosphorylation of acetyl-CoAcarboxylase were significantly elevated in hepatocytes treated with both BBR and G-Rb1. Consistent with the activationof AMPK, the mRNA expression of carnitine palmitoyl transferase 1 was stimulated, while the mRNA expression of3-hydroxy-3-methyl glutaryl coenzyme A reductase was suppressed. Pharmacokinetic analysis revealed that BBRincreased the bioavailability of G-Rb1 in Sprague-Dawley rats. Additionally, BBR prevented degradation of G-Rb1 infecal 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 auseful therapeutic agent for NAFLD.
