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

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Abstract

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 (˜ 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-γ, TNF-α and IL-1α 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 anti-oxidant activity as indicated by the significant (p < 0.05) increase in reduced glutathione. Finally, a significant (p < 0.05) decrease in IFN-γ, TNF-α, IL-1α 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 pro-inflammatory IL-1 and Il-18 pathways in addition to an antioxidant effect.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura, Egypt

    Nashwa Abu-Elsaad

  2. Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt

    Amr El-Karef

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  1. Nashwa Abu-Elsaad
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Correspondence to Nashwa Abu-Elsaad.

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Abu-Elsaad, N., El-Karef, A. Protection against nonalcoholic steatohepatitis through targeting IL-18 and IL-1alpha by luteolin. Pharmacol. Rep 71, 688–694 (2019). https://doi.org/10.1016/j.pharep.2019.03.009

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