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-κB)/NLR family pyrin domain-containing 3 (NLRP3) signaling pathway, thereby decreasing the release of interleukin (IL)-1β. 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-1β via inactivation of the hepatic TLR2/MyD88/NF-κB/NLRP3 signaling pathway.

Lagotis brachystachya Maxim is an herb widely used in traditional Tibet medicine. Our previous study indicated that total extracts from Lagotis brachystachya could lower uric acid levels. This study aimed to further elucidate the active components (luteolin, luteoloside and apigenin) isolated from Lagotis brachystachya and the underlying mechanism in vitro and vivo. The results showed that treatment with luteolin and luteoloside reversed the reduction of organic anion transporter 1 (OAT1) levels, while apigenin attenuated the elevation of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) levels in uric acid-treated HK-2 cells, which were consistent with the finding in the kidney of potassium oxonate (PO)-induced mice. On the other hand, hepatic xanthine oxidase activity was inhibited by the components. In addition, all of these active components improved the morphology of the kidney in hyperuricemic mice. Moreover, molecular docking showed that luteolin, luteoloside and apigenin could bind TLR4 and NLRP3. Consistently, western blot showed that the components inhibited TLR4/MyD88/NLRP3 signaling. In conclusion, these results indicated that luteolin, luteoloside and apigenin could attenuate hyperuricemia by decreasing the production and increasing the excretion of uric acid, which were mediated by the inhibition of inflammatory signaling pathways.