Faculty of Food Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China.
School of Basic Medicine, Kunming University of Science and Technology, Kunming 650500, China.
Nutrients. 2023 Sep 27;15(19):4176. doi: 10.3390/nu15194176.
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 ( 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.
酒精性肝病 (ALD) 是导致最常见慢性肝病的主要原因，它日益成为一个全球性的健康问题，这使得开发新型治疗方法的需求变得更加迫切。在此，我们旨在评估红米 ( L.) 种皮对 ALD 的治疗效果，并进一步揭示其潜在机制。采用柠檬酸-乙醇法提取红米种皮提取物 (RRA)，并通过广泛靶向成分分析进行分析。通过生物信息学分析预测 RRA 对 ALD 的潜在靶点。醉酒行为、组织病理学检查、肝功能、肠道微生物群落组成和肠道屏障完整性用于评估 RRA (RRAH，600mg/kg·体重；RRAL，200mg/kg·体重) 对 ALD 的影响。通过相应试剂盒、Western blot 和免疫荧光染色测量氧化应激、炎症、凋亡相关因素和信号通路。在 ALD 模型小鼠中，RRA 治疗可增加鞘氨醇激酶 2 (SPHK2) 和鞘氨醇-1-磷酸 (S1P) 水平，改善肠道微生物群落组成，恢复肠道屏障，降低血浆和肝脏中的脂多糖 (LPS) 水平，抑制 Toll 样受体 4 (TLR4)/核因子 kappa B (NF-κB) 途径，减轻肝脏病理损伤和氧化应激，减轻炎症和凋亡，增强肝功能。总之，RRA 靶向 SPHK2 通过修复肠道屏障损伤和降低 TLR4/NF-κB 途径和肠道微生物群中的肝 LPS 水平，可改善 ALD，这表明红米种皮具有作为预防和治疗 ALD 的功能性食品的潜力。
