Premium
Kaerophyllin inhibits hepatic stellate cell activation by apoptotic bodies from hepatocytes
Author(s) -
Lee TingFang,
Lin YunLian,
Huang YiTsau
Publication year - 2011
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2011.02485.x
Subject(s) - hepatic stellate cell , downregulation and upregulation , flow cytometry , protein kinase b , apoptosis , cell migration , microbiology and biotechnology , chemistry , hepatocyte , wound healing , cell , cancer research , biology , immunology , biochemistry , endocrinology , in vitro , gene
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.