TLR4 and alcoholic liver diseases: In an earlier study investigating alcoholic liver disease, treatment with citrate-ethanol-derived red rice seed skin extract (RRA) increased SPHK2 and S1P levels, improved gut microbiota composition, restored the integrity of the intestinal barrier, reduced plasma and liver LPS levels, and inhibited the activation of the Toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB) pathway, as well as alleviated liver pathological damage and oxidative stress, reduced inflammation and apoptosis, and enhanced liver function (136).