期刊
LIVER INTERNATIONAL
卷 31, 期 5, 页码 618-629出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1478-3231.2011.02485.x
关键词
Bupleurum scorzonerifolium; hepatic stellate cell; hepatocyte apoptosis; kaerophyllin liver fibrosis; migration; phagocytosis
资金
- National Science Council [NSC 96-2320-B-010-015-MY3, NSC 96-2628-B-077-001-MY2, NSC 97-2628-B-077-001, NSC 99-2628-B-077-001-MY3]
- National Research Institute of Chinese Medicine in Taiwan [NRICM99-DBCM-05]
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.
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