NHIBITION OF YIGANKANG, A COMBINATION OF CHINESE HERBS, ON PROLIFERATION OF RAT HEPATIC STELLATE CELLS INDUCED BY INTERLEUKIN-1Î’
Chinese blood-activating and stasis-eliminating herbal medicines have been used to treat liver fibrosis and have been reported to inhibit rat hepatic stellate cells (HSCs) proliferatio n. To study the mechanism of the proliferation inhibition of rat HSCs when using herbal medicine, the present study tried to evaluate the inhibition of Yigankang Decoction on c-Jun Nterminal kinase (JNK) and Activator protein-1 (AP-1) of rat hepatic stellate cells induced by interleukin-1β (IL-1β). The present study tried to evaluate the inhibition of Yigankang Decoction which contains blood-activating and stasiseliminating Chinese herbs such as large doses of Radix Salviae Miltiorrhizae (RSM) and Radix Angelicae Sinensis (RAS) on JNK and AP-1 in rat HSCs induced by IL-1β. Interleukin-1β up-regulated the proliferation of rat HSCs. After stimulation of IL -β for 24 h, the proliferation of rat HSCs increased significantly than the corresponding values in the control group (1.573 ± 0.026 vs. 1.390 ± 0.073, p < 0.01). After pretreated with the different concentrations of the JNK pathway’s inhibitor SP600125 (10 μmol/L, 1.427 ± 0.113; 20 μmol/L, 0.772 ± 0.093; 40 μmol/L, 0.675 ± 0.074), the proliferation of rat HSCs that were induced by IL-1β decreased significantly than the corresponding values in the control group (1.560±0.110) (p < 0.05; p < 0.01; p < 0.01). IL-1β activated the JNK pathway in a time-dependent manner in rat HSCs. After stimulation of IL-1β for 0, 5, 15, 30, 60 and 120 min, the JNK activities were 0.982 ± 0.299, 1.501 ± 0.720, 2.133 ± 0.882, 3.360 ± 0.452, 2.181 ± 0.789, 1.385 ± 0.368, respectively. In comparison with the group without IL-1β, the JNK activities differed significantly at 15, 30 and 60 min (p < 0.01, p < 0.01, p < 0.01). Yigankang Decoction inhibited the activities of JNK (1.610 ± 0.242 vs. 3.360 ± 0.452, p < 0.01) and AP-1 activity (342.43 ± 85.77 vs. 597.70 ± 83.96, p < 0.01) obviously. IL-1β can stimulate the proliferation of rat HSCs, and JNK/AP-1 signaling pathway is involved in the process. Therefore, Yigankang Decoction can inhibit HSCs proliferation, can be explained, in part, through JNK/AP-1 pathway