Inhibition of hepatic stellate cell activation following Yinchenhao decoction administration to dimethylnitrosamine-treated rats

Abstract

Aim: In an effort to investigate the mechanism by which Yinchenhao decoction (YCHD) acts on liver injury, we investigated the potential antifibrogenic effects of YCHD in an experimental liver fibrosis rat model, with special focus on the mechanisms inhibiting the activation and promoting apoptosis of hepatic stellate cells (HSC). Methods: The rats were initially randomized into two groups: the control (n = 10) and dimethylnitrosamine-treated (DMN; n = 30) groups. DMN (10 mg/kg body weight) was administered intraperitoneally to the DMN-treated rats for three consecutive days each week. At the end of the second week, three rats from the control and six rats from the DMN-treated groups were killed for the fibrosis development assessment. The remaining DMN rats were further randomized into two groups: the DMN-water group (n = 12) and the DMN-YCHD group (n = 12). Both groups continued to receive weekly DMN treatment for another 2 weeks in addition to daily administration of either water or YCHD, which were given intragastrically at a dose of 0.418 g/100 g body weight. Results: Hepatic hydroxyproline content decreased and had improved histopathology in the DMN-YCHD rats. Compared to the DMN group, α-smooth muscle actin (SMA) and CD68 expression in the DMN-YCHD group was reduced significantly; however, α-SMA-positive HSC apoptosis was not observed by confocal microscopy; Fibrogenic proteins (tissue inhibitor matrix proteinases-1 and 2 and matrix metalloproteinase [MMP]-2/14) and cytokines (tumor necrosis factor-α and transforming growth factor-β1) were decreased; MMP-9 was significantly upregulated. Conclusion: Yinchenhao administration attenuates liver fibrosis at least in part by inhibiting HSC activation directly, rather than promoting cell apoptosis of activated HSC, and the suppressive activation of Kupffer cells. © 2008 The Japan Society of Hepatology.