Effects of combined dietary supplementation with fenofibrate and Schisandrae Fructus pulp on lipid and glucose levels and liver function in normal and hypercholesterolemic mice

BACKGROUND Currently, combined therapy using herbs and synthetic drugs has become a feasible therapeutic intervention against some diseases. The purpose of this study was to assess the effects of supplementation with fenofibrate (FF), a chemical drug used for the treatment of hyperlipidemia, and the aqueous extract of Schisandrae Fructus (SF, a Chinese herb) pulp (AqSF-P) or an SF-related synthetic analog, bicyclol (BY), on serum/hepatic lipid levels and liver status in normal and hypercholesterolemic (HCL) mice. METHODS Male mice obtained from the Institute of Cancer Research (ICR) were fed on a normal diet (ND) or high cholesterol/bile salt (0.5%/0.15%, w/w) diet (HCBD) containing FF (0.03% or 0.1%, w/w) with or without AqSF-P (0.3%-9.0%, based on crude herbal material, w/w) or BY (0.025%, w/w) for 10 days. Then serum lipid levels and alanine aminotransferase (ALT) activity, as well as hepatic triglyceride (TG), total cholesterol (TC), and glucose levels, were measured. RESULTS Oral supplementation with FF significantly reduced serum and hepatic TG, TC, and hepatic glucose levels (approximately 79%) in mice fed with ND or HCBD. FF supplementation combined with AqSF-P or BY increased FF-induced reduction in hepatic TC and TG contents in ND-fed mice (up to 67%) and in HCBD-fed mice (up to 54%), when compared with FF supplementation alone. Hepatic glucose-lowering effect of FF was enhanced (up to 19%) by AqSF-P cosupplementation in both normal and HCL mice. FF supplementation enhanced the excretion of fecal TC (by 75%) in mice fed with HCBD. Fecal TC contents were increased by 14%/9% in the combination therapy with FF and AqSF-P in ND-/HCBD-fed mice. Serum ALT activity was elevated by 45% in HCBD-fed mice. FF caused a significant increase in ALT activity by 198% and 120% in normal and HCL mice, respectively. BY markedly attenuated the ALT activity by 54% in mice fed with ND supplemented with 0.1% FF and by 42% in mice fed with HCBD supplemented with 0.03% FF. CONCLUSION AqSF-P cosupplementation augmented the hepatic lipid-/glucose-lowering effects of FF. BY ameliorated FF-induced liver injury in normal and HCL mice.