期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 47, 期 -, 页码 126-133出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.intimp.2017.03.029
关键词
Liver fibrosis; Quercetin; NF-kappa B; p38 MAPK, apoptosis pathway
资金
- National Natural Science Foundation of China [81303192]
- Science and Technology Commission of Shanghai Baoshan District [14-E-5]
- Shanghai Municipal Commission of Health and Family Planning [201540306]
Quercetin, a natural flavonoid, has been used as a nutritional supplement for its anti-inflammatory and antioxi-dative properties. Quercetin was reported to exhibit a wide range of pharmacological properties, including its effect on anti-hepatic fibrosis. However, the anti-fibrotic mechanisms of quercetin have not been well characterized to date. This study aimed to investigate the protective effects of quercetin on carbon tetrachloride (CCl4)-induced liver fibrosis in rats and to clarify its anti-hepatofibrotic mechanisms. We demonstrated that quercetin exhibited in-vivo hepatoprotective and anti-fibrogenic effects against CCl4-induced liver injury by improving the pathological manifestations, thereby reducing the activities of serum total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and decreasing the serum levels of hyaluronic acid (HA), laminin (LN), type IV collagen (IV-C) and procollagen III peptide (PIIIP). Furthermore, treatment with quercetin 5-15 mg/kg inhibited the activation of NF-kappa B in a dose-dependent manner via inhibition of Ha degradation and decreased the expression of p38 MAPK by inhibiting its phosphorylation. Additionally, in a dose dependent manner, quercetin down-regulated Bax, up-regulated Bcl-2, and subsequently inhibited caspase-3 activation. Moreover, quercetin regulated inflammation factors and hepatic stellate cells (HSCs)-activation markers, such as TNF-alpha, IL-6, IL-1 beta, Cox-2, TGF-beta, alpha-SMA, Coital, Colla2, TIMP-1, MMP-1, and desmin. Taken together, quercetin prevented the progression of liver fibrosis in SD rats. The anti-fibrotic mechanisms of quercetin might be associated with its ability to regulate NF-kappa B/I kappa B alpha, p38 MAPK anti-inflammation signaling pathways to inhibit inflammation, and regulate Bcl-2/Bax anti-apoptosis signaling pathway to prevent liver cell apoptosis. (C) 2017 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据