Oxymatrine ameliorates non-alcoholic fatty liver disease in rats through peroxisome proliferator-activated receptor-α activation

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common type of liver disease worldwide. Recent studies have reported that oxymatrine (OMT), an active monomer isolated from Sophora flavescens Ait. (kushen), ameliorates NAFLD in rats. In order to explore the possible molecular mechanism involved, we used an NAFLD rat model with hyperlipidemia, which had been established by feeding a high‑fructose diet (HFD) for eight weeks, and the model rats were subsequently treated with OMT (80 mg/kg/day) for a further four weeks. We evaluated the expression of genes and proteins regulating fatty acid oxidation and lipid export in the liver using quantitative (q)PCR and western blot analysis. The NAFLD model rats developed dyslipidaemia, hepatic steatosis and insulin resistance (IR). OMT administration for four weeks reduced body weight gain and visceral fat weight, decreased serum triglyceride (TG), total cholesterol (TC), free fatty acid (FFA) and fasting serum insulin (FinS) levels and lowered liver TG contents. It also increased the glucose infusion rate (GIR), indicative of a reduction in IR. Moreover, OMT treatment markedly increased the mRNA and protein levels of peroxisome proliferator-activated receptor-α (PPARα), carnitine palmitoyltransferase 1A (CPT1A) and microsomal triglyceride transfer protein (MTTP). The beneficial effects of OMT were further confirmed by the observation of a decrease in lipid accumulation in the histology of the liver. Our results indicate that OMT may be used to treat NAFLD.

Oxymatrine Improves Intestinal Epithelial Barrier Function Involving NF-κB-Mediated Signaling Pathway in CCl4-Induced Cirrhotic Rats

“…Several preclinical studies have evaluated its beneficial effects and investigated the underlying mechanism. Shi et al [17], [18] showed that oxymatrine simultaneously down-regulated sterol regulatory element binding transcription factor 1 and up-regulated peroxisome proliferator activated receptor alpha mediated metabolic pathways to attenuate hepatic steatosis in rats with non-alcoholic fatty liver disease. It has been reported that oxymatrine protected animals against ischemia and reperfusion-induced liver, heart, and intestinal injuries involving extracellular signal regulated kinase, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinases signaling pathways [19]–[21].…”

Efficacy of oxymatrine for treatment and relapse suppression of severe plaque psoriasis: results from a single-blinded randomized controlled clinical trial

“…and increase the level of IL‐10 in patients with chronic HBV infection, which might be one of the mechanisms of action in reversing liver fibrosis . The satisfactory efficacy/toxicity profile of oxymatrine, together with its economic viability, make it a good candidate for the management of complex diseases …”

Decreased MiR-155 Level in the Peripheral Blood of Non-Alcoholic Fatty Liver Disease Patients may Serve as a Biomarker and may Influence LXR Activity

“…LXRα can bind the retinoid X receptor (RXR), thereby activating the transcription of downstream genes [7]. In the liver, LXRα is found to activate SREBP-1 gene transcription, which then enhances the subsequent activation of lipogenic genes, including fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC1), and stearoyl-coenzyme A desaturase (SCD-1) [8].…”