Osthole ameliorates hepatic fibrosis and inhibits hepatic stellate cell activation.

Ya-Wei Liu,Yi-Tsau Huang,Shu-Ling Fu,Yung-Tsung Chiu

doi:10.1186/s12929-015-0168-5

Ya-Wei Liu, Yi-Tsau Huang + Show 2 more

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https://doi.org/10.1186/s12929-015-0168-5

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Abstract

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

Highlights

Hepatic fibrosis is a dynamic process which leads to cirrhosis in almost patients with chronic hepatic injury
Studies indicated that the pathology of TAA-induced liver injury is similar in some ways to that of cirrhosis in human [16]. We investigated both the in vivo and in vitro effects of osthole in hepatic fibrotic rats induced by TAA, and hepatic stellate cell (HSC) activated by tumor necrosis factor-α (TNF-α), tumor growth factorβ1 (TGF-β1), or ET-1
We further assessed the effect of osthole treatment on liver injury by biochemical analyses of plasma enzymes

Summary

Introduction

Hepatic fibrosis is a dynamic process which leads to cirrhosis in almost patients with chronic hepatic injury. 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. Hepatic fibrosis is a dynamic wound-healing response to chronic hepatic injuries such as alcoholism and viral hepatitis in patients. Activation of hepatic stellate cells (HSCs) is the prevailing process during hepatic fibrosis [2]. Activated HSCs generate fibrosis by accumulating extracellular matrix (ECM), secreting cytokines and chemokines, and enhancing the ability of chemotaxis [3]. HSCs could be triggered to transdifferentiate from quiescent into activated form by inflammatory mediators or growth factors, such as tumor necrosis factor-α (TNF-α), tumor growth factorβ (TGF-β1) and endothelin-1 (ET-1) [5,6,7]

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