Sasa quelpaertensis leaves ameliorate alcohol-induced liver injury by attenuating oxidative stress in HepG2 cells and mice.

Oxidative stress plays a crucial role in the progression of alcoholic liver diseases and substances of antioxidant property are of special interest for therapeutic purposes. We investigated the hepatoprotective effect of leaf extracts of Sasa quelpaertensis, an edible bamboo mainly cultivated in Jeju Island, South Korea. We examined the cytotoxicity of different extracts (distilled water, 20-80% EtOH) of S. quelpaertensis on HepG2 cells and their hepatoprotective effect on HepG2 cells stimulated by ethanol (800 mM, 24 h). Furthermore, we measured reactive oxygen species (ROS) production, ethanol toxicity induced cell death, and the activity of antioxidant enzymes. In in vivo experiments, liver damage was induced by oral administration of 5 g/kg ethanol with or without potent ethanol extract of S. quelpaertensis (10 or 100 mg/kg) 12 h interval for a total of 3 doses. Only 80% ethanol extract of S. quelpaertensis (SQEE80) exhibited cytoprotective effect on HepG2 cells against alcohol-induced toxicity. SQEE80 treatment (250, 500 µg/mL) in ethanol exposed HepG2 cells showed significant attenuation of ROS production and ethanol toxicity induced cell death. Furthermore, SQEE80 markedly increased the activity of antioxidant enzyme glutathione peroxidase 1 in ethanol exposed HepG2 cells compared to ethanol stimulated cells. In in vivo experiments, SQEE80 treatment evidently suppressed the alcohol-induced histopathological changes in liver, serum ethanol content, and expression of cytochrome P450 2E1. Furthermore, SQEE80 significantly reversed the reduction of glutathione level in the ethanol challenged liver. Taken together, we suggest the possibility of developing SQEE80 as a natural hepatoprotective substance in attenuating alcohol-induced oxidative stress.

Phenolic acid and flavonoid-rich fraction of Sasa quelpaertensis Nakai leaves prevent alcohol induced fatty liver through AMPK activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Sasa quelpaertensis Nakai is an edible dwarf bamboo cultivated mainly in Jeju Island, South Korea and its leaf displays various health-promoting properties including antioxidant scavenging. AIM OF THE STUDY: In this study, we aimed at elucidating its hepatoprotective effect against alcohol-induced fatty liver. METHODS: In in vitro study, we evaluated the cytotoxicity and hepatoprotective effect of different solvent fractions (aqua, butanol, chloroform, ethyl acetate and hexane) of 80% EtOH extract of S. quelpaertensis Nakai leaf. In vivo experiment performed using binge alcohol consumption model. RESULTS: Although all five fractions (0-1000 µg/mL) were non-cytotoxic to HepG2 cells, only ethyl acetate fraction (SQEA), rich in phenolic acids such as p-coumaric acid and flavonoids particularly myristin, showed hepatoprotective effect against EtOH (400 mM) in HepG2 cells. Furthermore, SQEA significantly decreased the ethanol induced cell death and enhanced the cell proliferation. In in vivo experiment using binge consumption model (5 g of EtOH/kg body weight in every 12 h for 3 times), SQEA treatment (10, 50 and 100 mg/kg) markedly reduced the alcohol induced histopathological changes and serum EtOH content, and reversed the reduction of glutathione level in ethanol challenged livers. Further, it suppressed the expression of cytochrome P450 2E1 (CYP2E1). In particular, SQEA activated AMP activated protein kinase (AMPK) pathway, and decreased the expression of tumor necrosis factor receptor-1 (TNFR1), which attenuated lipogenesis via decreased expression of fatty acid synthase (FAS). Inhibited lipogenesis due to SQEA treatment directed towards decreased perilipin-2 expression. These results indicate that SQEA has hypolipidemic effect which is mediated by decreased oxidative stress, increased fatty acid oxidation response and decreased lipogenesis. CONCLUSION: Our results suggest the possibility of developing SQEA as a natural hepatoprotective agent potent in attenuating alcohol-induced fatty liver.