Involvement of Toll-like Receptor 2/Myeloid Differentiation Factor 88/Nuclear Factor kappa B/NLR Family Pyrin Domain-containing 3 Signaling Pathways in the Hepatoprotective Effect of Lagotis brachystachys in Rats with Alcoholic Liver Disease

Background: Excessive consumption of alcohol is ranked as one of the leading causes of death from alcoholic liver disease (ALD). Our previous study demonstrated that the whole extracts of Lagotis brachystachys decreased acute hepatic injury in rats. However, the compounds of the extracts that are responsible for the hepatoprotective activity and their underlying mechanism are still unknown. Objectives: The objective of the study was to evaluate the hepatoprotective effect of whole extracts of L. brachystachys against chronic alcohol-induced ALD in rats. Materials and Methods: Different polar compounds of ethanolic extract from L. brachystachys were orally administered to rats that underwent 8 weeks of alcohol exposure. Results: The histological evaluation of rat liver showed that the rats exposed to 30% and 50% ethanolic extracts of L. brachystachys had significantly less formation of lipid droplets and showed less inflammatory infiltration than that of control rats with ALD. The extracts also inhibited alcohol-induced elevation of serum lipid peroxidation levels. In addition, L. brachystachys restored the levels of antioxidants and inhibited the alcohol-induced activation of the hepatic Toll-like receptor 2 (TLR2)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-.B)/NLR family pyrin domain-containing 3 (NLRP3) signaling pathway, thereby decreasing the release of interleukin (IL)-1 beta. Conclusion: Our data revealed that L. brachystachys showed hepatoprotective effect against chronic alcohol-induced hepatic injury by decreasing the levels of lipid peroxidation and oxidative stress and by inhibiting the inflammatory processes. The extracts decreased the release of IL-1 beta via inactivation of the hepatic TLR2/MyD88/NF-.B/NLRP3 signaling pathway.