BACKGROUND

Alisma orientale (Sam.) Juzepczuk (Alismataceae) is an indigenous medicinal herb that has been traditionally used for diuretic, hypolipidemic, anti-inflammatory, and antidiabetic proposes in northern and eastern Asia.

OBJECTIVE

This study examined the mechanisms underlying the cytoprotective effect of an aqueous extract of A. orientale (AEAO) against long-chain saturated fatty acid-induced cellular injury.

METHODS

HepG2 cells were treated with 0.5 mM palmitate to generate a cellular model of nonalcoholic fatty liver disease (NAFLD). Using this cellular model, the cytoprotective effect of AEAO (100 µg/mL) against long-chain saturated fatty acid-induced cellular injury was evaluated by measuring the steatosis, ROS accumulation, and apoptosis.

RESULTS

AEAO significantly attenuated palmitate-induced intracellular steatosis and cellular damage up to 54 and 33%, respectively. Palmitate-induced intracellular levels of reactive oxygen species (ROS) and reactive aldehydes were significantly reduced in the presence of AEAO to 40 and 75%, respectively, suggesting that oxidative stress plays a role in the palmitate-induced damage. AEAO inhibited the palmitate-mediated activation of c-Jun NH(2)-terminal kinase (JNK), a kinase that is correlated with NAFLD. Inhibition of JNK by SP600125 or addition of AEAO significantly reduced palmitate-induced steatosis, ROS accumulation, and apoptosis, indicating that the protective effects of AEAO against palmitate-induced cellular damage result from blocking ROS-activated JNK signaling.

CONCLUSIONS

The combined properties of AEAO in cellular steatosis and ROS production are beneficial for treating NAFLD, which includes complex metabolic changes, such that modulation of a single target is often not sufficient to achieve the desired therapeutic effect.