Osthole ameliorates hepatic fibrosis and inhibits hepatic stellate cell activation

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.

Electronic supplementary material

The online version of this article (doi:10.1186/s12929-015-0168-5) contains supplementary material, which is available to authorized users.     

Proline and hepatic lipogenesis

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酒精与肝脏脂质代谢

酒精滥用是一个重大的公共健康问题。酒精通过刺激脂肪酸合成,抑制脂肪酸的氧化导致肝脏脂质积累,进而诱发肝细胞病变,导致脂肪肝的病发。从转录调控脂质代谢的改变,异常甲硫氨酸代谢对内质网应激反应的作用等方面概述酒精与脂质代谢的相互调控机制,并阐述了这些调控机制之间的内在联系以及酒精如何影响肝脏脂质代谢,从而导致脂肪肝形成的最新相关研究进展。     

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General anesthesia and hepatic circulation

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Species differences in hepatic glutathione depletion, covalent binding and hepatic necrosis after acetaminophen

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