摘要
背景:Hesperetin是柑橘类水果的天然成分,可作为转化生长因子β(TGF-β)抑制剂,对损伤和各种癌症具有有益的抗炎作用。然而,几乎没有证据表明hesperetin与肝纤维化有关。 目的:我们实验室的工作旨在寻找橙皮素减轻肝纤维化的机制。 方法:采用胆管结扎法(BDL)诱导小鼠肝纤维化,采用酶联免疫吸附试验,定量实时聚合酶链反应,免疫印迹和免疫组化染色检测结果。结果:免疫组化染色和损伤评分数据表明,橙皮素治疗可减少病理损害。降低几种血清参数水平,包括细胞因子肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6),肝酶丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST),纤维化指标层粘连蛋白(LN),透明质酸(HA)和羟脯氨酸(Hyp)表明与免疫组化相似的结果。此外,我们的数据证实,hesperetin可以抑制体外细胞外基质和肝细胞凋亡的形成,同时促进体内肝星状细胞死亡,这被认为与抑制TGF-β1/ Smad通路有关。 结论:在本研究中,从柑橘皮中提取的橙皮素的有利作用被证实可以通过抑制TGF-β1/ Smad途径介导的细胞外基质进展和凋亡来预防BDL诱导的肝纤维化的进展。
关键词: 肝硬化,橙皮素,抗炎作用,细胞外基质,肝纤维化,细胞凋亡。
Current Molecular Medicine
Title:Hesperetin Mitigates Bile Duct Ligation-Induced Liver Fibrosis by Inhibiting Extracellular Matrix and Cell Apoptosis via the TGF-β1/Smad Pathway
Volume: 18 Issue: 1
关键词: 肝硬化,橙皮素,抗炎作用,细胞外基质,肝纤维化,细胞凋亡。
摘要: Background: Hesperetin, a natural component of citrus fruits, is indicated to have beneficial anti-inflammatory effects on injury and various cancers as a transforming growth factor beta (TGF-β) inhibitor. However, little evidence associates hesperetin with liver fibrosis.
Objective: Work from our laboratory aims at finding the mechanism by which hesperetin attenuates liver fibrosis.
Methods: Bile duct ligation (BDL) was used to induce liver fibrosis in mice and the findings were determined using enzyme-linked immunosorbent assay, quantitative realtime polymerase chain reaction, western blotting and immunohistochemical staining.
Results: Data from Immunohistochemical staining and injury score indicated that pathological lesions were reduced by hesperetin treatment. Decreasing levels of several serum parameters including cytokines tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), liver enzyme alanine aminotransferase (ALT) and aspartate aminotransferase (AST), fibrosis indicators laminin (LN), hyaluronic acid (HA) and hydroxylproline (Hyp) suggested similar results to the immunohistochemical. In addition, our data verified hesperetin could suppress the formation of extracellular matrix and hepatocyte apoptosis in vitro, together with promoting hepatic stellate cell death in vivo, which was considered to be associated with the inhibition of TGF-β1/Smad pathways.
Conclusion: In the present study, the favorable role of hesperetin extracted from citrus peels was verified to prevent the progression of BDL-induced liver fibrosis via inhibiting TGF-β1/Smad pathway-mediated extracellular matrix progression and apoptosis.
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Cite this article as:
Hesperetin Mitigates Bile Duct Ligation-Induced Liver Fibrosis by Inhibiting Extracellular Matrix and Cell Apoptosis via the TGF-β1/Smad Pathway, Current Molecular Medicine 2018; 18 (1) . https://dx.doi.org/10.2174/1566524018666180608084947
DOI https://dx.doi.org/10.2174/1566524018666180608084947 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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