Red Rice Seed Coat Targeting SPHK2 Ameliorated Alcoholic Liver Disease via Restored Intestinal Barrier and Improved Gut Microbiota in Mice

Abstract

Alcoholic liver disease (ALD), leading to the most common chronic liver diseases, is increasingly emerging as a global health problem, which is intensifying the need to develop novel treatments. Herein, our work aimed to estimate the therapeutic efficacy of red rice (Oryza sativa L.) seed coat on ALD and further uncover the underlying mechanisms. Red rice seed coat extract (RRA) was obtained with citric acid–ethanol and analyzed via a widely targeted components approach. The potential targets of RRA to ALD were predicted by bioinformatics analysis. Drunken behavior, histopathological examination, liver function, gut microbiota composition and intestinal barrier integrity were used to assess the effects of RRA (RRAH, 600 mg/kg·body weight; RRAL, 200 mg/kg·body weight) on ALD. Oxidative stress, inflammation, apoptosis associated factors and signaling pathways were measured by corresponding kits, Western blot and immunofluorescence staining. In ALD model mice, RRA treatment increased sphingosine kinase 2 (SPHK2) and sphingosine-1-phosphate (S1P) levels, improved gut microbiota composition, restored intestinal barrier, decreased lipopolysaccharide (LPS) levels in plasma and the liver, cut down Toll-like receptor 4 (TLR4)/Nuclear factor kappa B (NF-κB) pathways, alleviated liver pathological injury and oxidative stress, attenuated inflammation and apoptosis and enhanced liver function. To sum up, RRA targeting SPHK2 can ameliorate ALD by repairing intestinal barrier damage and reducing liver LPS level via the TLR4/NF-κB pathway and intestinal microbiota, revealing that red rice seed coat holds potential as a functional food for the prevention and treatment of ALD.

Comparative Metabolic Profiling of Different Colored Rice Grains Reveals the Distribution of Major Active Compounds and Key Secondary Metabolites in Green Rice

“…Pigmented rice grains have been used as key ingredients in traditional medicine in Korea, China, and Japan since ancient times to treat anemia and diabetes, enhance kidney function and blood circulation, and relieve blood congestion [ 7 ]. Supportively, pharmacological investigations have shown that pigmented rice, especially black and red rice, possess antioxidant, anti-diabetic, anti-hypertension, cardioprotective, anticancer, antiallergic, anti-hyperlipidemia, antitumor, antiatherosclerosis, and protective effects against alcoholic liver disease [ 8 , 9 , 10 , 11 , 12 , 13 ]. Unfortunately, although there is evidence for the higher nutritional and therapeutic values of pigmented rice compared to white rice, the global metabolome differences between the different colored rice remain not well elucidated, limiting their use in specific dietary formulations and food pharmacy programs.…”