Hepatoprotective effect of Trigonella foenum graecum against ethanol-induced cell death in human liver cells (HepG2 and Huh7)

Background The plant Trigonella foenum graecum, also known as fenugreek, has been shown to have anticancer, antidiabetic, anti-inflammatory, and antioxidant properties. In this study, the hepatoprotective effect of fenugreek seed extract (FSE) against ethanol-induced cell death was investigated in human liver cells (HepG2 and Huh7). Methods and results The cytotoxic effect of FSE and ethanol on cells was evaluated by exposing the cells at different concentrations. Following that, the cells were pre-incubated with 5-25 mu g/ml FSE, followed by a cytotoxic concentration (0.5 mM) of ethanol. MTT and neutral red uptake assays were performed in treated cells to assess the ability of FSE to protect cells from the cytotoxic effects of ethanol. When compared to controls, ethanol treatment significantly reduced the viability of HepG2 and Huh7 cells and altered the cell morphology, whereas treatment with FSE significantly increased cell viability and reversed ethanol-induced morphological changes. Furthermore, pretreatment with FSE dose-dependently reduced lactate dehydrogenate (LDH) leakage, lipid peroxidation (LPO) level, and catalase activities while increasing glutathione (GSH) level induced by ethanol. Pretreatment with FSE also reduced the generation of reactive oxygen species (ROS), caspase enzyme activities, and protein expression of caspase-3 and -9. In HepG2 cells, ethanol-induced apoptosis was observed, whereas FSE treatment reduced apoptosis by downregulating the expression of pro-apoptotic marker genes and upregulating the antiapoptotic gene. Conclusions In conclusion, this study reports on the mechanistic details of the hepatoprotective potential of FSE. The results also suggest that fenugreek seeds may be useful in preventing liver diseases caused by toxicants such as ethanol.