Jian Tunyu, Ao Xiancan, Wu YueXian, Lv Han, Ma Li, Zhao Lei, Tong Bei, Ren Bingru, Chen Jian, Li Weilin
Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing, 210014, China.
Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing, 210014, China.
Biomed Pharmacother. 2017 Jul;91:229-237. doi: 10.1016/j.biopha.2017.04.056. Epub 2017 Apr 28.
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by hepatic steatosis, which affects 20-40% of the population in the world. Loquat (Eriobotrya japonica) Leaf possesses several pharmacological actions. Many sesquiterpene glycosides were reported to be isolated exclusively from the Loquat Leaf, however, their biological activity has been rarely investigated. The present study was designed to evaluate the pharmacological effect of total sesquiterpene glycosides (TSG) in high-fat diet (HFD) induced NAFLD mice with its related mechanisms of action. Mice were fed with a normal diet or HFD for 8 weeks. TSG (25 and 100mg/kg/day), simvastatin (10mg/kg/day) or vehicle were orally administered for last 4 weeks of the 8-week HFD feeding period. From the result, it was showed that TSG significantly reduced the body weight and fat deposition in the liver of NAFLD mice. It also decreased total cholesterol (TC) and triglyceride (TG) contents in the serum. Compared with NAFLD mice, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were increased and decreased after the administration of TSG in a dose of 100mg/kg, respectively. TSG reduced alanine aminotransferase (ALT) activity as well. Finally, TSG was found to suppress the expression of cytochrome P450 2E1 (CYP2E1) and the phosphorylation of c-jun terminal kinase (JNK) in NAFLD mice. In summary, this study demonstrates that TSG reduces oxidative stress by downregulating of CYP2E1 expression and JNK phosphorylation in NAFLD, and alleviates NAFLD ultimately. TSG potentially serves as bioactive compounds for the treatment of NAFLD.
非酒精性脂肪性肝病（NAFLD）是一种以肝脂肪变性为特征的慢性肝病，影响着全球20%-40%的人口。枇杷（Eriobotrya japonica）叶具有多种药理作用。据报道，许多倍半萜糖苷仅从枇杷叶中分离得到，然而，它们的生物活性很少被研究。本研究旨在评估总倍半萜糖苷（TSG）对高脂饮食（HFD）诱导的NAFLD小鼠的药理作用及其相关作用机制。将小鼠喂以正常饮食或高脂饮食8周。在8周高脂饮食喂养期的最后4周，口服给予TSG（25和100mg/kg/天）、辛伐他汀（10mg/kg/天）或赋形剂。结果表明，TSG显著降低了NAFLD小鼠的体重和肝脏脂肪沉积。它还降低了血清中总胆固醇（TC）和甘油三酯（TG）的含量。与NAFLD小鼠相比，给予100mg/kg剂量的TSG后，超氧化物歧化酶（SOD）水平升高，丙二醛（MDA）水平降低。TSG也降低了丙氨酸转氨酶（ALT）的活性。最后，发现TSG可抑制NAFLD小鼠细胞色素P450 2E1（CYP2E1）的表达和c-jun末端激酶（JNK）的磷酸化。总之，本研究表明，TSG通过下调NAFLD中CYP2E1的表达和JNK的磷酸化来降低氧化应激，并最终减轻NAFLD。TSG有可能作为治疗NAFLD的生物活性化合物。
