Education and Research Center for Clinical Pharmacy, Kobe Pharmaceutical University, 4-19-1 Motoyamakitamachi, Higashinada-ku, Kobe 658-8558, Japan.
Laboratory of Medical Pharmaceutics, Kobe Pharmaceutical University, 4-19-1 Motoyamakitamachi, Higashinada-ku, Kobe 658-8558, Japan.
Mar Drugs. 2019 Feb 9;17(2):104. doi: 10.3390/md17020104.
Nonalcoholic steatohepatitis (NASH) progresses from nonalcoholic fatty liver disease (NAFLD); however, efficacious drugs for NASH treatment are lacking. Sodium alginate (SA), a soluble dietary fiber extracted from brown algae, could protect the small intestine from enterobacterial invasion. NASH pathogenesis has been suggested to be associated with enterobacterial invasion, so we examined the effect of SA on methionine- and choline-deficient (MCD) diet-induced steatohepatitis in mice (the most widely-used model of NASH). The mice ( = 31) were divided into three groups (mice fed with regular chow, MCD diet, and MCD diet premixed with 5% SA) for 4 and 8 weeks. The MCD diet increased lipid accumulation and inflammation in the liver, the NAFLD Activity Score and hepatic mRNA expression of tumor necrosis factor- and collagen 11, and induced macrophage infiltration. Villus shortening, disruption of zonula occludens-1 localization and depletion of mucus production were observed in the small intestine of the MCD-group mice. SA administration improved lipid accumulation and inflammation in the liver, and impaired barrier function in the small intestine. Collectively, these results suggest that SA is useful for NASH treatment because it can prevent hepatic inflammation and fatty degeneration by maintaining intestinal barrier function.
非酒精性脂肪性肝炎（NASH）由非酒精性脂肪性肝病（NAFLD）进展而来；然而，缺乏有效的 NASH 治疗药物。褐藻提取的可溶性膳食纤维藻酸钠（SA）可保护小肠免受肠杆菌入侵。NASH 的发病机制与肠杆菌入侵有关，因此我们研究了 SA 对蛋氨酸和胆碱缺乏（MCD）饮食诱导的小鼠脂肪性肝炎（最广泛使用的 NASH 模型）的影响。将小鼠（ = 31）分为三组（常规饮食、MCD 饮食和 MCD 饮食预混 5% SA）喂养 4 周和 8 周。MCD 饮食增加了肝脏的脂质积累和炎症，NAFLD 活动评分和肿瘤坏死因子-α和胶原 1α1 的肝 mRNA 表达，并诱导了巨噬细胞浸润。MCD 组小鼠的小肠绒毛缩短、紧密连接蛋白-1 定位破坏和粘液生成减少。SA 给药可改善肝脏的脂质积累和炎症，并损害小肠的屏障功能。综上所述，这些结果表明，SA 可用于 NASH 治疗，因为它可以通过维持肠道屏障功能来预防肝脏炎症和脂肪变性。
