Use of herbal remedies in the treatment of various diseases has a long tradition in Eastern medicine and the
liver diseases are not an exception. In their use, lack of elucidation of mechanism(s) as well as randomized, placebo-controlled clinical trials has been a problem. Recently, we and others reported that inchin-ko-to (TJ-135), one of herbal remedies, suppressed hepatic
fibrosis in animal models. In the course of clarifying the mechanism, we directed our focus on hepatic stellate cells (HSCs), playing a pivotal role in hepatic
fibrosis, and found that rat HSCs cultured with
TJ-135 changed their morphology to star-like configuration with thin, slender and dendritic processes with fewer stress fibers, which might be the features in apoptosis. In fact,
TJ-135 induced HSC apoptosis in a time- and concentration-dependent manner as judged by the nuclear morphology, quantitation of cytoplasmic
histone-associated
DNA oligonucleosome fragments and
caspase 3 activity. In HSCs treated with
TJ-135, increased expression of p53 and decreased expression of Bcl-2 and phosphorylated Akt and Bad were determined. HSC apoptosis is shown to be involved in the mechanisms of spontaneous resolution of rat hepatic
fibrosis and the agent which induces HSC apoptosis has been shown to reduce experimental hepatic
fibrosis in rats. Thus, the induction of HSC apoptosis could be the mechanism how
TJ-135 works on the resolution of hepatic
fibrosis. Our current data may shed light on the novel effect of the herbal remedy.