Puerarin mediates hepatoprotection against CCl4-induced hepatic fibrosis rats through attenuation of inflammation response and amelioration of metabolic function

Puerarin mediates hepatoprotection against CCl4-induced hepatic fibrosis rats through attenuation of inflammation response and amelioration of metabolic function
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DOI:
10.1016/j.fct.2012.10.059
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发表时间:
2013-02-01
影响因子:
4.3
通讯作者:
Duan, Xiaoqun
Duan, Xiaoqun
中科院分区:
农林科学2区
文献类型:
--
作者:
Li, Rong;Xu, Lingyuan;Duan, Xiaoqun

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本研究旨在评价葛根素(Puerarin,PR)对四氯化碳(CCl_4,2 mL·kg ~(-1)·d ~(-1))诱导的大鼠肝纤维化(HF)的治疗作用。与模型对照组相比,PR治疗组能有效降低HF大鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、白蛋白(Alb)、总蛋白(TP)水平。Masson染色分析表明,HF大鼠的病情得到缓解。PR干预后,肿瘤坏死因子α(TNF-α)、核因子-κ B(NF-κ B)的表达在蛋白水平上明显下调。肝组织超氧化物歧化酶(SOD)活性升高,丙二醛(MDA)含量降低。如免疫组织化学分析所示,PR治疗导致转化生长因子-β I(TGF-β I)的产生减少。RT-PCR分析表明,诱导型一氧化氮合酶(induciblenitricoxidesynthase,iNOS)mRNA表达水平降低也是其作用机制之一。这些结果表明,葛根素通过调节血清酶和减弱TNF-α/NF-κ B通路的抗炎反应以及改善肝组织的代谢功能,成功地逆转了CCl 4诱导的HF大鼠的肝毒性。(C)2012爱思唯尔有限公司版权所有。
This study was designed to evaluate the potential effects of puerarin (PR), an effective isoflavonoid compound purified from Pueraria lobata, in treating hepatic fibrosis (HF) rats induced by carbon tetrachloride (CCl4, 2 mL kg(-1) d(-1)). Compared to model control, PR treatment effectively lowered the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb), total protein (TP) in HF rats. Masson stained analysis showed that the condition of HF rats was mitigated. Meanwhile, the tumor necrosis factor alpha (TNF-alpha), nuclear factor-kappa B (NF-kappa B) expressions were significantly down-regulated at protein level by PR intervention. Additionally, the activity of superoxide dismutase (SOD) was elevated, while the content of malondialdehyde (MDA) was lessened in liver tissue. As revealed by immunohistochemistry assay, PR therapy resulted in reduced production of transforming growth factor-beta I (TGF-beta I). Moreover, it also was attributed to decreased mRNA level of inducible nitric oxide synthase (iNOS) using RT-PCR analysis. These findings demonstrate that puerarin successfully reverses hepatotoxicity in CCl4-induced HF rats via the underlying mechanisms of regulating serum enzymes and attenuating TNF-alpha/NF-kappa B pathway for anti-inflammation response, as well as improving metabolic function in liver tissue. (C) 2012 Elsevier 'Ltd. All rights reserved.