Zhou Yuyan, Sun Yu, Li Ping, Qin Guozheng, Cheng Qian, Liu Yu, Chen Yingli, Wang Guodong
Drug Research & Development Center/School of Pharmacy, Wannan Medical College, Wuhu, 241002, China.
Anhui Provincial Engineering Research Center for Polysaccharide Drugs/Anhui Provincial Key Laboratory of Active Biological Macro-molecules, Wuhu 241002, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2018 Jul 30;38(8):949-955. doi: 10.3969/j.issn.1673-4254.2018.08.08.
To investigate the protective effect of monoside against triptolide-induced liver injury and explore its molecular mechanism.
BALB/C mice treated with gastric lavage with triptolide and monoside, either alone or in combination, were examined for changes of hepatic biochemical parameters using the serological method. The growth inhibition rate of HepG2 cells treated with triptolide or monoside or both was assessed with MTT assay, and the cell morphological changes were observed using laser confocal microscopy; the expressions of the target proteins in the antioxidative stress pathway were detected using flow cytometry and Western blotting.
In BALB/C mice, gastric lavage of triptolide induced obvious hepatic damage. In HepG2 cells, treatment with triptolide significantly inhibited the cell growth, resulting in a cell viability as low as 72.83% at 24 h; triptolide also induced obvious cell apoptosis and cell nucleus deformation, causing an apoptosis rate of 43.1% in the cells at 24 h. Triptolide significantly reduced the expressions of Nrf2 and HO-1 proteins related with the oxidative stress pathway. Combined treatment with morroniside obviously reversed these changes, resulting in significantly decreased hepatic biochemical parameters and the liver index in BALB/C mice and in significantly lowered cell apoptosis rate, improved cell morphology, and increased Nrf2 and HO-1 protein expressions in HepG2 cells.
Monoside protects against triptolide-induced liver injury possibly by relieving oxidative stress.
研究莫诺苷对雷公藤甲素诱导的肝损伤的保护作用，并探讨其分子机制。
采用灌胃法给予BALB/C小鼠雷公藤甲素和莫诺苷，单独给药或联合给药，采用血清学方法检测肝脏生化指标的变化。采用MTT法检测雷公藤甲素或莫诺苷或两者联合处理的HepG2细胞的生长抑制率，并用激光共聚焦显微镜观察细胞形态变化；采用流式细胞术和蛋白质免疫印迹法检测抗氧化应激途径中靶蛋白的表达。
在BALB/C小鼠中，灌胃雷公藤甲素可导致明显的肝损伤。在HepG2细胞中，雷公藤甲素处理显著抑制细胞生长，24 h时细胞活力低至72.83%；雷公藤甲素还诱导明显的细胞凋亡和细胞核变形，24 h时细胞凋亡率为43.1%。雷公藤甲素显著降低了与氧化应激途径相关的Nrf2和HO-1蛋白的表达。莫诺苷联合处理明显逆转了这些变化，导致BALB/C小鼠的肝脏生化指标和肝脏指数显著降低，HepG2细胞的细胞凋亡率显著降低，细胞形态改善，Nrf2和HO-1蛋白表达增加。
莫诺苷可能通过减轻氧化应激来保护雷公藤甲素诱导的肝损伤。
