Shu Xiangbing, Wang Miao, Xu Hanchen, Liu Yang, Huang Jie, Yao Zemin, Zhang Li
Institute of Digestive Diseases, China-Canada Center of Research for Digestive Diseases (ccCRDD), Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
Department of Biochemistry, Microbiology & Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON, Canada K1H 8M5.
Evid Based Complement Alternat Med. 2017;2017:9208314. doi: 10.1155/2017/9208314. Epub 2017 Jul 31.
Nonalcoholic steatohepatitis (NASH) is featured by the presence of hepatic steatosis combined with inflammation and hepatocellular injury. Gut-derived endotoxin plays a crucial role in the pathogenesis of NASH. Salvia-Nelumbinis naturalis (SNN), a formula of Traditional Chinese Medicine, has been identified to be effective for NASH, but the mechanisms were not thoroughly explored. In the present study, a NASH model was generated using C57BL/6 mice fed a high fat diet (HFD) supplemented periodically with dextran sulfate sodium (DSS) in drinking water for 12 weeks. Mice fed HFD alone (without DSS) or chow diet were used as controls. The NASH mice were given the SNN extracts in the following 4 weeks, while control mice were provided with saline. Mice fed HFD developed steatosis, and DSS supplementation resulted in NASH. The SNN extracts significantly improved metabolic disorders including obesity, dyslipidemia, and liver steatosis and reduced hepatic inflammation, circulating tumor necrosis factor- (TNF-), and lipopolysaccharide (LPS) levels. The beneficial effect of the SNN extracts was associated with restoration of intestinal conditions (microbiota, integrity of intestinal barrier) and inhibition of TLR4/NF-B activation. These results suggest that the SNN extracts ameliorate NASH progression, possibly through blocking endotoxin related TLR4/NF-B activation.
非酒精性脂肪性肝炎（NASH）的特征是存在肝脂肪变性并伴有炎症和肝细胞损伤。肠道来源的内毒素在NASH的发病机制中起关键作用。中药配方丹参荷叶（SNN）已被证实对NASH有效，但其作用机制尚未得到充分研究。在本研究中，使用C57BL/6小鼠建立NASH模型，给小鼠喂食高脂饮食（HFD），并在饮水中定期补充硫酸葡聚糖钠（DSS），持续12周。单独喂食HFD（不补充DSS）或普通饮食的小鼠作为对照。在接下来的4周内，给NASH小鼠给予SNN提取物，而对照小鼠给予生理盐水。喂食HFD的小鼠出现脂肪变性，补充DSS导致NASH。SNN提取物显著改善了包括肥胖、血脂异常和肝脂肪变性在内的代谢紊乱，并降低了肝脏炎症、循环肿瘤坏死因子-（TNF-）和脂多糖（LPS）水平。SNN提取物的有益作用与肠道状况（微生物群、肠道屏障完整性）的恢复以及TLR4/NF-κB激活的抑制有关。这些结果表明，SNN提取物可能通过阻断与内毒素相关的TLR4/NF-κB激活来改善NASH的进展。
