Osthole ameliorates hepatic fibrosis and inhibits hepatic stellate cell activation

Journal of Biomedical Science

Yi-Tsau Huang²  Shu-Ling Fu¹  Yung-Tsung Chiu³  Ya-Wei Liu¹ 

[1] Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, No. 155, Li-Nong Street, Sec. 2, Taipei 11221, Taiwan;National Research Institute of Chinese Medicine, Ministry of Health and Welfare, No. 155-1, Li-Nong Street, Sec. 2, Taipei 11221, Taiwan;Department of Medical Research and Education, Taichung Veterans General Hospital, No. 1650, Taiwan Boulevard Sec. 4, Taichung 40705, Taiwan

关键词: Inflammation;    Hepatic stellate cells;    Hepatic fibrosis;    Osthole;    Cnidium monnieri (L.) Cusson;   

Others  :  1221740
DOI  :  10.1186/s12929-015-0168-5

 received in 2015-02-05, accepted in 2015-07-16,  发布年份 2015

【 摘 要 】

Background

Hepatic fibrosis is a dynamic process which ultimately leads to cirrhosis in almost patients with chronic hepatic injury. However, progressive fibrosis is a reversible scarring response. Activation of hepatic stellate cells (HSCs) is the prevailing process during hepatic fibrosis. Osthole is an active component majorly contained in the fruit of Cnidium monnieri (L.) Cusson. This present study investigated the therapeutic effects of osthole on rat liver fibrosis and HSC activation.

Results

We established the thioacetamide (TAA)-model of Sprague–Dawley (SD) rats to induce hepatic fibrosis. Rats were divided into three groups: control, TAA, and TAA + osthole (10 mg/kg). In vivo, osthole significantly reduced liver injury by diminishing levels of plasma AST and ALT, improving histological architecture, decreasing collagen and α-SMA accumulation, and improving hepatic fibrosis scores. Additionally, osthole reduced the expression of fibrosis-related genes significantly. Osthole also suppressed the production of fibrosis-related cytokines and chemokines. Moreover, nuclear translocation of p65 was significantly suppressed in osthole-treated liver. Osthole also ameliorated TAA-induced injury through reducing cellular oxidation. Osthole showed inhibitory effects in inflammation-related genes and chemokines production as well. In vitro, we assessed osthole effects in activated HSCs (HSC-T6 and LX-2). Osthole attenuated TGF-β1-induced migration and invasion in HSCs. Furthermore, osthole decreased TNF-α-triggered NF-κB activities significantly. Besides, osthole alleviated TGF-β1- or ET-1-induced HSCs contractility.

Conclusions

Our study demonstrated that osthole improved TAA-caused liver injury, fibrogenesis and inflammation in rats. In addition, osthole suppressed HSCs activation in vitro significantly.

【 授权许可】

   
2015 Liu et al.

【 图 表 】

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