A Chinese Herbal Decoction, Modified Yi Guan Jian, Induces Apoptosis in Hepatic Stellate Cells through an ROS‐Mediated Mitochondrial/Caspase Pathway

Abstract

The Chinese herb modified Yi Guan Jian (mYGJ) is an effective regimen that is usually used in outpatients with chronic liver diseases such as fibrosis and cirrhosis. However, the mechanism for the action of mYGJ on liver fibrosis is not yet clear. In this study, we found that mYGJ induced hepatic stellate cells (HSCs) apoptosis concomitant with the downregulation of Bcl-2 expression and slight elevation of Bax level. Moreover, the reactive oxygen species (ROS) were generated in the early stages of mYGJ-induced HSCs apoptosis to facilitate calcium and cytochrome c release from the mitochondria to cytosol. Subsequently, caspase 9 and caspase 3 were activated. Furthermore, the activation of ER stress-associated caspase 12 in HSCs was also evaluated. Together, we report the first evidence-based study to demonstrate that mYGJ decoction induces HSCs apoptosis through ROS accumulation and the intrinsic apoptosis pathway. These findings provide rationale for further clinical investigation of traditional Chinese medicine recipes against liver fibrosis.

A Chinese herbal medicine, Gexia-Zhuyu Tang (GZT), prevents dimethylnitrosamine-induced liver fibrosis through inhibition of hepatic stellate cells proliferation

“…6) in proportion to the reduced production of collagens and stellate cell activity. This result is consistent with results obtained by Lin et al, 2011a, b that showed Yi Guan Jian (YGJ) reduced collagen deposition in the DMN model of hepatic fibrosis. The reduced fibrosis was associated with reduced alpha-SMA expression and type I procollagen expression in the liver.…”

Paeonol inhibits hepatic fibrogenesis via disrupting nuclear factor‐κB pathway in activated stellate cells: In vivo and in vitro studies

“…As shown in Figure c,d, a dose‐dependent increase in early apoptotic (annexin V+/PI−) cells in the presence of paeonol was observed and that paeonol at 20 μmol/L resulted in significant apoptosis. The mitochondria play a crucial role in cell apoptosis pathway . Treatment with paeonol caused HSCs to loss the mitochondrial membrane potential in a dose‐dependent manner (Fig.…”

Hepatoprotective effects of Yi Guan Jian, an herbal medicine, in rats with dimethylnitrosamine-induced liver fibrosis

“…The extract was decanted, filtered under vacuum, concentrated in a rotary evaporator, and then lyophilized. The concentration for final stock solution of YGJ extract was 175 mg/ml (Lin et al, 2011).…”

“…Furthermore, HSC apoptosis may also play a central role in the spontaneous recovery from biliary fibrosis (Issa et al, 2001). Therefore, it is important to discover the apoptosis mechanisms of HSC treated by traditional Chinese herbal medicines that might resolve progressive HSC proliferation and matrix synthesis (Lin et al, 2011).…”