Protection against nonalcoholic steatohepatitis through targeting IL-18 and IL-1alpha by luteolin

Background: The management of nonalcoholic steatohepatitis (NASH) is still a crosstalk so the current study was designed to evaluate the effect of different luteolin doses on an experimental model of NASH and to elucidate novel anti-inflammatory pathways underlying its effect. Methods: Adult male Wistar rats (200-220 g; n = 60) were used. Rats were fed a high carbohydrate/high fat diet ((similar to)30% carbohydrate and 42% fat) daily for 12 weeks to induce NASH. Luteolin (10, 25, 50 or 100 mg/kg/day) was administered as a suspension (10% w/v in 0.9% NaCl) using an oral gavage. Histopathological changes (necrosis, inflammation and steatosis) were evaluated. Biomarkers for liver function, lipid peroxidation, extracellular matrix deposition and anti-oxidant activity were measured. Levels of IFN-gamma, TNF-alpha and IL-1 alpha and IL-18 were measured. Results: Obtained results showed ability of luteolin to reduce activity of ALT and AST and to decrease levels of bilirubin, hyaluronic acid and malondialdehyde significantly (p < 0.05). Also, luteolin showed an antioxidant activity as indicated by the significant (p < 0.05) increase in reduced glutathione. Finally, a significant (p < 0.05) decrease in IFN-gamma, TNF-alpha, IL-1 alpha and IL-18 levels was observed most notably in groups that received high doses of luteolin (50 and 100 mg/kg). Conclusions: Luteolin can protect against non-alcoholic steatohepatitis through targeting the proinflammatory IL-1 and Il-18 pathways in addition to an antioxidant effect. (C) 2019 Maj Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.