Osthole ameliorates hepatic fibrosis and inhibits hepatic stellate cell activation.
Osthole ameliorates hepatic fibrosis and inhibits hepatic stellate cell activation.
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DOI：
10.1186/s12929-015-0168-5
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发表时间：
2015-08-01
影响因子：
11
通讯作者：
Huang YT
中科院分区：
文献类型：
--
作者：
Liu YW;Chiu YT;Fu SL;Huang YT
肝纤维化是一个动态过程，几乎在慢性肝损伤患者中最终导致肝硬化。然而，进行性纤维化是一种可逆的疤痕反应。肝星状细胞（HSC）的激活是肝纤维化过程中的主要过程。蛇床子素是主要存在于蛇床子(Cnidium monnieri (L.) Cusson)果实中的活性成分。本研究探讨了蛇床子素对大鼠肝纤维化和 HSC 活化的治疗作用。我们建立了 Sprague-Dawley (SD) 大鼠的硫代乙酰胺 (TAA) 模型来诱导肝纤维化。将大鼠分为三组：对照组、TAA 组和 TAA + 蛇床子素 (10 mg/kg)。在体内，蛇床子素通过降低血浆 AST 和 ALT 水平、改善组织学结构、减少胶原蛋白和 α-SMA 积累以及改善肝纤维化评分，显着减少肝损伤。此外，蛇床子素还能显着降低纤维化相关基因的表达。蛇床子素还抑制纤维化相关细胞因子和趋化因子的产生。此外，在蛇床子素处理的肝脏中，p65 的核易位被显着抑制。蛇床子素还通过减少细胞氧化来改善 TAA 引起的损伤。蛇床子素对炎症相关基因和趋化因子的产生也表现出抑制作用。在体外，我们评估了蛇床子素对活化 HSC（HSC-T6 和 LX-2）的作用。蛇床子素可减弱 TGF-β1 诱导的 HSC 迁移和侵袭。此外，蛇床子素显着降低 TNF-α 触发的 NF-κB 活性。此外，蛇床子素还能减轻 TGF-β1 或 ET-1 诱导的 HSC 收缩性。我们的研究表明，蛇床子素可改善 TAA 引起的大鼠肝损伤、纤维形成和炎症。此外，蛇床子素在体外显着抑制HSCs活化。本文的在线版本 (doi:10.1186/s12929-015-0168-5) 包含补充材料，可供授权用户使用。
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. 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. Our study demonstrated that osthole improved TAA-caused liver injury, fibrogenesis and inflammation in rats. In addition, osthole suppressed HSCs activation in vitro significantly. The online version of this article (doi:10.1186/s12929-015-0168-5) contains supplementary material, which is available to authorized users.