Kaerophyllin inhibits hepatic stellate cell activation by apoptotic bodies from hepatocytes
Ting-Fang Lee
Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan
Search for more papers by this authorYun-Lian Lin
National Research Institute of Chinese Medicine, Taipei, Taiwan
*Both Yi-Tsau Huang and Yun-Lian Lin contributed equally to this work and are considered co-senior authors.
Search for more papers by this authorYi-Tsau Huang
Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan
National Research Institute of Chinese Medicine, Taipei, Taiwan
*Both Yi-Tsau Huang and Yun-Lian Lin contributed equally to this work and are considered co-senior authors.
Search for more papers by this authorTing-Fang Lee
Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan
Search for more papers by this authorYun-Lian Lin
National Research Institute of Chinese Medicine, Taipei, Taiwan
*Both Yi-Tsau Huang and Yun-Lian Lin contributed equally to this work and are considered co-senior authors.
Search for more papers by this authorYi-Tsau Huang
Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan
National Research Institute of Chinese Medicine, Taipei, Taiwan
*Both Yi-Tsau Huang and Yun-Lian Lin contributed equally to this work and are considered co-senior authors.
Search for more papers by this authorAbstract
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.
Supporting Information
Fig. S1. Kaerophyllin inhibited TGF-β1, PDGF-BB or TNF-α-induced LX-2 activation. Effects of kaerophyllin on (A) TGF-β1-induced α-SMA expression was detected by immuboblotting, (B) PDGF-BB-induced proliferation measured by BrdU incorporation and (C) TNF-α induced NF-κB activity were evaluated by luciferase assays. # <0.05, TGF-β1, PDGF-BB or TNF-α compared with control; * <0.05, AB+different concentrations of kaerophyllin compared with TGF-β, PDGF or TNF-α group, n=3.
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