*Both Yi-Tsau Huang and Yun-Lian Lin contributed equally to this work and are considered co-senior authors.
Kaerophyllin inhibits hepatic stellate cell activation by apoptotic bodies from hepatocytes
Article first published online: 3 MAR 2011
© 2011 John Wiley & Sons A/S
Volume 31, Issue 5, pages 618–629, May 2011
How to Cite
Lee, T.-F., Lin, Y.-L. and Huang, Y.-T. (2011), Kaerophyllin inhibits hepatic stellate cell activation by apoptotic bodies from hepatocytes. Liver International, 31: 618–629. doi: 10.1111/j.1478-3231.2011.02485.x
- Issue published online: 3 APR 2011
- Article first published online: 3 MAR 2011
- Received 16 August 2010, Accepted 27 January 2011
- Bupleurum scorzonerifolium;
- hepatic stellate cell;
- hepatocyte apoptosis;
- liver fibrosis;
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 α-smooth muscle actin, upregulated profibrogenic gene transcriptions and increased NF-κB activity, cell migration and phagocytosis. Kaerophyllin from BS antagonized AB-induced HSC migration and activation.
Conclusions: Kaerophyllin inhibited AB-induced LX-2 activation and migration with downregulation of Akt/ERK phosphorylations and NF-κB activity. Our study suggests a novel platform for screening anti-fibrotic compounds with ABs.