Li Long, Yin Hongyan, Zhao Yan, Zhang Xiaofang, Duan Chaoli, Liu Jing, Huang Caoxin, Liu Suhuan, Yang Shuyu, Li Xuejun
Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen UniversityXiamen 361003, China.
Institute of Drug Discovery Technology, Ningbo UniversityNingbo 315211, China.
Am J Transl Res. 2018 Mar 15;10(3):957-965. eCollection 2018.
Acute liver injury is a destructive liver disorder resulting from overwhelming liver inflammation, oxidative stress and hepatocyte death. Puerarin is a natural flavonoid compound isolated from the traditional Chinese herb radix puerariae. This study investigated the protective effects of puerarin against lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced liver injury and the potential mechanisms in mice. Mice were given an intraperitoneal administration of puerarin 200 mg/kg 2 h prior to LPS (50 μg/kg)/D-Gal (400 mg/kg) injection and were sacrificed 6 h post LPS/D-Gal treatment. The results showed that administration of puerarin substantially alleviated LPS/D-Gal-induced acute liver injury in mice by increased survival rates, improved liver histopathology, reduced plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, alleviated production of pro-inflammatory cytokines, and suppressed hepatocyte apoptosis. Moreover, puerarin pretreatment activated autophagy by increased the ratio of LC3B-II/I and the protein levels of Beclin-1, decreased the levels of p62 protein expression. Taken together, these findings demonstrated that puerarin could prevent the LPS/D-Gal-induced liver injury in mice, and its mechanisms might be associated with the increments of autophagy and suppression of apoptosis.
急性肝损伤是一种由严重的肝脏炎症、氧化应激和肝细胞死亡导致的肝脏破坏性疾病。葛根素是从传统中药葛根中分离出的一种天然黄酮类化合物。本研究探讨了葛根素对脂多糖(LPS)/D-半乳糖胺(D-Gal)诱导的小鼠肝损伤的保护作用及其潜在机制。在注射LPS(50μg/kg)/D-Gal(400mg/kg)前2小时,给小鼠腹腔注射200mg/kg葛根素,并在LPS/D-Gal处理后6小时处死小鼠。结果表明,葛根素给药可通过提高存活率、改善肝脏组织病理学、降低血浆丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)水平、减轻促炎细胞因子的产生以及抑制肝细胞凋亡,显著减轻LPS/D-Gal诱导的小鼠急性肝损伤。此外,葛根素预处理通过提高LC3B-II/I的比率和Beclin-1的蛋白水平激活自噬,降低p62蛋白表达水平。综上所述,这些发现表明葛根素可以预防LPS/D-Gal诱导的小鼠肝损伤,其机制可能与自噬增加和凋亡抑制有关。