Kaerophyllin inhibits hepatic stellate cell activation by apoptotic bodies from hepatocytes

Background: Hepatic stellate cells (HSCs), the key cell type for hepatic fibrosis, become activated and profibrogenic in the presence of hepatocyte apoptotic bodies (ABs). Bupleurum scorzonerifolium (BS), a widely used traditional Chinese herb for liver diseases, was fractionated, and the inhibitory effects of BS extracts on AB-induced HSC migration were screened. The activity-guided fractionation led to a lignan, kaerophyllin. In this study, the anti-fibrotic effects of kaerophyllin were studied in the presence of ABs. Methods: LX-2 cells phagocytosing ultraviolet (UV)-induced HepG2 ABs were investigated by confocal microscopy and flow cytometry. AB-induced HSC activation was evaluated by immunoblotting and real-time PCR analyses. HSC migration was measured by wound-healing assays. Results: HepG2 ABs induced LX-2 activation, with the production of collagen I and a-smooth muscle actin, upregulated profibrogenic gene transcriptions and increased NF-kappa B activity, cell migration and phagocytosis. Kaerophyllin from BS antagonized ABinduced HSC migration and activation. Conclusions: Kaerophyllin inhibited AB-induced LX-2 activation and migration with downregulation of Akt/ERK phosphorylations and NF-kappa B activity. Our study suggests a novel platform for screening anti-fibrotic compounds with ABs.