Naringenin reduces cholesterol-induced hepatic inflammation in rats by modulating matrix metalloproteinases-2, 9 via inhibition of nuclear factor κB pathway

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of hepatic abnormalities that extends from isolated steatosis to non-alcoholic steatohepatitis (NASH) and steatofibrosis. NASH is the progressive form of the disease that can lead to fibrosis, cirrhosis and hepatocellular carcinoma. Naringenin (NGEN), a healthful food, increases resistance to oxidative stress, inflammation and protects against multiple organ injury in various animal models. However, specific mechanisms responsible for such effects are poorly understood. Thus, this study investigates the effect of treatment with NGEN (50 mg/kg) on oxidative events and the molecular mechanisms underlying inflammatory changes triggered in the rat liver by a high cholesterol diet for 90 days. NGEN significantly decreased the plasma fatty acid composition, the hepatic pro-inflammatory mediators and the expression of relevant genes including tumor necrosis factor-α, interlukin-6, interleukin-1β, inducible nitric oxide synthase and matrix metalloproteinases (MMP-2, 9), EGF-like module-containing mucin-like hormone receptor-like 1 (macrophage F4/80-specific gene); which suggests a reduced macrophage infiltration, and inhibited oxidative stress related biomarker levels at the end point of the experiment. Mechanistically, studies showed that NGEN markedly reduced lipid and protein oxidations, recruited the anti-oxidative defense system and promoted extracellular matrix degradation by modulating the levels of necrotic inflammation.