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Involvement of P450s and nuclear receptors in the hepatoprotective effect of quercetin on liver injury by bacterial lipopolysaccharide.
Immunopharmacology and Immunotoxicology ( IF 2.9 ) Pub Date : 2020-04-07 , DOI: 10.1080/08923973.2020.1742154
Ling Zhao 1 , Fang Chen 1 , Yuanli Zhang 1 , Ling Yue 1 , Hongrui Guo 1 , Gang Ye 1 , Fei Shi 1 , Cheng Lv 1 , Bo Jing 1 , Huaqiao Tang 1 , Zhongqiong Yin 1 , Hualin Fu 1 , Jvchun Lin 1 , Yinglun Li 1 , Xun Wang 2
Affiliation  

Objective: Quercetin (Que), a flavonoid, possesses anti-inflammatory and antioxidant properties. It has been shown to protect against liver injury induced by various factors. This study was designed to investigate the underlying mechanism of its protective effect against lipopolysaccharide (LPS)- induced liver damage.Methods: Mice were pretreated with Que for 7 consecutive days and then exposed to LPS. To study the hepatoprotective effect of Que, oxidative stress parameters, inflammatory cytokine levels in liver and serum liver function indexes were examined. Protein and mRNA expression of nuclear orphan receptors and cytochrome P450 enzymes were measured by Western Blotting and qPCR, respectively.Results: Que significantly reduced circulating ALT, AST, ALP, and ameliorated LPS-induced histological alterations. In addition, Que obviously decreased markers of oxidative stress and pro-inflammatory cytokines. Furthermore, Que carried out the hepatoprotective effect via regulation of the expression of nuclear orphan receptors (CAR, PXR) and cytochrome P450 enzymes (CYP1A2, CYP2E1, CYP2D22, CYP3A11).Conclusions: Our findings suggested that Que pretreatment could ameliorate LPS-induced liver injury.

中文翻译:

P450和核受体参与槲皮素对细菌性脂多糖肝损伤的肝保护作用。

目的:类黄酮槲皮素具有抗炎和抗氧化作用。已经证明它可以防止各种因素引起的肝损伤。本研究旨在探讨其对脂多糖(LPS)诱导的肝损伤的保护作用的潜在机制。方法:对小鼠进行连续7天的Que预处理,然后使其暴露于LPS。为了研究Que的保肝作用,研究了氧化应激参数,肝脏炎症细胞因子水平和血清肝功能指标。Western Blotting和qPCR分别检测核孤儿受体和细胞色素P450酶的蛋白质和mRNA表达。结果:Que显着降低了循环ALT,AST,ALP和减轻的LPS诱导的组织学改变。此外,Que明显降低了氧化应激和促炎细胞因子的标志物。此外,Que通过调节核孤儿受体(CAR,PXR)和细胞色素P450酶(CYP1A2,CYP2E1,CYP2D22,CYP3A11)的表达来发挥保肝作用。结论:我们的研究结果表明Que预处理可以改善LPS诱导的肝脏受伤。
更新日期:2020-04-07
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