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

Abstract

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.

Keywords: bicyclol; fat index; fatty liver disease; hepatotoxicity; interaction; synergist.

Figure 1

Experimental design of the study. Abbreviations: SF-P, Schisandrae Fructus pulp; AqSF-P, aqueous extract of SF-P; BY, bicyclol; TC, total cholesterol; TG, triglyceride; HDL, high-density lipoprotein; LDL, low-density lipoprotein; N-HDL, non-high-density lipoprotein; ALT, alanine aminotransferase; ND, normal diet; HCBD, high cholesterol/bile salt diet.

Figure 2

Effects of dietary supplementation with FF, FF/AqSF-P, and FF/BY on hepatic lipid and glucose levels in normal and hypercholesterolemic mice. Notes: Mice were fed with ND or HCBD without and with supplementation with FF or the combination of FF and AqSF-P or BY at the indicated concentrations. Ten days later, hepatic TC (A), TG (B), and glucose (C) levels were measured. Values given are the means ± SEM, with n=10. *P<0.05, **P<0.01 vs ND; ^##P<0.01 vs HCBD; ^†P<0.05, ^††P<0.01 vs FF alone. Statistically significant differences were determined using a one-way ANOVA, followed by Dunnett’s multiple-comparisons test. Abbreviations: ND, normal diet; HCBD, high cholesterol/bile salt (0.5%/0.15%, w/w) diet; FF, fenofibrate; AqSF-P, aqueous extract of Schisandrae Fructus pulp; BY, bicylol; TC, total cholesterol; TG, triglyceride; SEM, standard error of mean; ANOVA, analysis of variance; w/w, weight/weight; vs, versus.

Figure 2

Effects of dietary supplementation with FF, FF/AqSF-P, and FF/BY on hepatic lipid and glucose levels in normal and hypercholesterolemic mice. Notes: Mice were fed with ND or HCBD without and with supplementation with FF or the combination of FF and AqSF-P or BY at the indicated concentrations. Ten days later, hepatic TC (A), TG (B), and glucose (C) levels were measured. Values given are the means ± SEM, with n=10. *P<0.05, **P<0.01 vs ND; ^##P<0.01 vs HCBD; ^†P<0.05, ^††P<0.01 vs FF alone. Statistically significant differences were determined using a one-way ANOVA, followed by Dunnett’s multiple-comparisons test. Abbreviations: ND, normal diet; HCBD, high cholesterol/bile salt (0.5%/0.15%, w/w) diet; FF, fenofibrate; AqSF-P, aqueous extract of Schisandrae Fructus pulp; BY, bicylol; TC, total cholesterol; TG, triglyceride; SEM, standard error of mean; ANOVA, analysis of variance; w/w, weight/weight; vs, versus.

Figure 3

Effects of dietary supplementation with FF, FF/AqSF-P, and FF/BY on fecal cholesterol excretion in normal and hypercholesterolemic mice. Notes: Mice were fed with ND or HCBD without and with supplementation with FF or the combination of FF and AqSF-P or BY at the indicated concentration. Ten days later, fecal TC content was measured. Values given are the means ± SEM, with n=10. *P<0.05, **P<0.01 vs ND; ^#P<0.05, ^##P<0.01 vs HCBD. Statistically significant differences were determined using a one-way ANOVA, followed by Dunnett’s multiple-comparisons test. Abbreviations: ND, normal diet; HCBD, high cholesterol/bile salt (0.5%/0.15%, w/w) diet; FF, fenofibrate; AqSF-P, aqueous extract of Schisandrae Fructus pulp; BY, bicyclol; TC, total cholesterol; TG, triglyceride; SEM, standard error of mean; vs, versus; ANOVA, analysis of variance; w/w, weight/weight.