Loquat fruit peel extract regulates lipid metabolism and liver oxidative stress in mice: In vivo and in silico approaches.

Abstract

In Moroccan traditional medicine, fresh or dried loquat (Eriobotrya japonica (Thunb.) Lindl.) fruit peels infused in water and taken for 45 days are used as natural remedies against hypercholesterolemia, hyperglycemia and cardiovascular diseases. This is the first experimental study approving the folk medicinal use of loquat fruit peels originated from eastern Morocco. The study aims to investigate the effect of loquat fruit peel extract on lipid metabolism and liver oxidative status in mice as well as to predict the possible mechanisms. The study was carried out using high fat/fructose diet-induced hyperlipidemic mice model treated with the loquat peel extract for 45 days at two doses (100 and 200mg/kg/day) in comparison to fenofibrate drug. The plasma, tissue, fecal and biliary lipids and blood glucose were analyzed using enzymatic methods. The liver oxidative status was evaluated and the polyphenol profiling was conducted using the HPLC-DAD method. Possible mechanisms involved in the observed pharmacological effects were predicted by in silico method. The extract at a dose of 200mg/kg possessed higher effect than at 100mg/kg. It significantly reduced plasma total cholesterol (TC), triglycerides (TG), LDL-cholesterol, atherogenic index, LDL-C/HDL-C ratio and plasma glucose (-36%, -45%, -45%, -82%, -87%, 58%, respectively), while the HDL-cholesterol was increased (+172%). Moreover, the extract reduced TC and TG in the liver and adipose tissue by increasing their excretion in bile and fecal matter. It prevented the liver oxidative stress and decreased body weight and organ relative mass. The extract appears to be nontoxic (LD50>5000mg/kg) and contains five polyphenols including ferulic acid (32.74±0.71mg/g), caffeic acid (21.48±0.32mg/g), 5-O-Caffeoylquinic acid (112.15±1.86mg/g), chlorogenic acid (42.05±0.92mg/g) and quercetin (32.69±0.68mg/g). These phenolics and/or their circulating metabolites presented differential interaction capacities with the potential enzymes and transcription factors implicated in lipid homeostasis such as HMG-CoA reductase, lipoprotein lipase, fatty acid synthase, Cyp7a1, ABCG, PPARs, RXR, FXR and RAR. Our findings justify the traditional use of loquat fruit peels and suggest that their aqueous extract could be used as substrate to produce phytotherapeutic drugs or dietary supplements to prevent hyperlipidemia, hyperglycemia and related cardiovascular diseases.