Eugenol modulates insulin sensitivity by upregulating insulin receptor substrate-2 in non-alcoholic fatty liver disease in rats.

OBJECTIVES The purpose of this study was to estimate the possible modulatory effect of Eugenol (EUG) on insulin resistance (IR) and liver fibrosis in high-fat diet (HFD)-induced experimental non-alcoholic fatty liver disease (NAFLD) in rats. It has been shown that EUG, a natural phenolic compound, has anti-hyperglycaemic, antioxidant and anti-inflammatory actions. METHODS For 8 consecutive weeks, standard rat chow diet (control group, EUG only treated group) or HFD (HFD group and HFD+EUG-treated group) were fed to rats daily. HFD+EUG-treated group and EUG only treated group were administered EUG (10 mg/kg) orally three times per week. Various indices of hepatotoxicity, oxidative stress, indicators of inflammation and liver fibrosis were investigated. KEY FINDINGS HFD-induced liver transaminases and triglycerides (TGs) were significantly decreased and histopathological lesions were improved with EUG treatment. EUG significantly improved IR evoked by HFD, as demonstrated by Homeostasis model assessment for insulin resistance (HOMA-IR) and increased insulin receptor substrate-2 (IRS-2) sensitivity. In addition, EUG improved oxidative stress damage elicited by HFD as shown by the restoration of reduced glutathione (GSH) level and nuclear factor erythroid-2-related factor 2 (Nrf-2) expression and plummeting lipid peroxidation. Further, EUG lessened pro-inflammatory cytokines surge [tumour necrosis factor-α (TNF-α) and IL-6] via inhibiting nuclear factor-κB (NF-κB) stimulation. As markers of fibrosis, EUG reduced collagen accumulation and smooth muscle alpha actin (SMaA) and TGF-β expression. CONCLUSIONS EUG may have protective effect against progression of fibrosis in NAFLD. The antifibrotic effect of EUG is probably due to EUG's antioxidant, anti-inflammatory and anti-hyperglycaemic.