Apoptotic effects of hsian-tsao (Mesona procumbens Hemsley) on hepatic stellate cells mediated by reactive oxygen species and ERK, JNK, and caspase-3 pathways

The activation of hepatic stellate cells (HSCs) is an important step in the progress of liver fibrosis. Fibrosis can be impeded by HSC reversion to a quiescent state or HSC clearance through apoptosis. To investigate the apoptotic effects of hsian-tsao (Mesona procumbens Hemsl) on human HSCs, the expression levels of cleaved caspase-3, p38, and c-Jun N-terminal kinase (JNK) were assessed using Western blotting, and the caspase-3 activity was measured using caspase-3/CPP32 colorimetric assay kit. Hsian-tsao extract (HTE) increased the activity of caspase-3 and the level of activated caspase-3, indicating the activation of apoptosis. The intracellular reactive oxygen species (ROS) level increased in a dose-dependent manner. This increase was prevented by an antioxidant, suggesting that HTE induces ROS accumulation. In addition, we found that HTE induced the phosphorylation of the mitogen-activated protein kinases JNK and p38. These collective data indicate that HTE induces apoptosis via ROS production through the p38, JNK, and caspase-3-dependent pathways. HTE may decrease HSC activation in liver fibrosis and may have a therapeutic potential.