乳香酸调节NOX/p38 MAPK/PPARα通路和miR-155表达减轻实验性酒精性肝病小鼠模型中的肝损伤:新的机制见解

IF 6.9 3区 医学 Q1 CHEMISTRY, MEDICINAL
Rania M. Salama, Samah S. Abbas, Samar F. Darwish, Al Aliaa Sallam, Noura F. Elmongy, Sara A. El Wakeel
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引用次数: 5

摘要

酒精性肝病(ALD)是指由过量饮酒引起的肝脏疾病。ALD的发病机制包括各种机制途径之间的复杂相互作用,其中炎症和氧化应激是关键因素。在锯状Boswellia serrata中发现的Boswellic acids(BA)由于其抗氧化和抗炎活性而显示出保肝作用,然而,它们对ALD的治疗潜力此前尚未得到研究。因此,本研究旨在描述BA可能的保护作用,并在实验诱导的ALD小鼠模型中检测其潜在的作用机制。雄性BALB/c小鼠被平等地分为六组:对照组、BA治疗组、ALD组和ALD组,它们通过经口灌胃接受三个剂量水平(125、250和500 mg/kg)的BA,持续14天。结果显示,从组织病理学检查、血液酒精浓度(BAC)和肝功能酶来看,高剂量BA对ALD的保护作用最大。机制研究显示,BA(500 mg/kg)导致细胞色素P450 2E1(CYP2E1)、尼古丁腺嘌呤二核苷酸磷酸氧化酶(NOX)1/2/4、p38丝裂原活化蛋白激酶(MAPK)和固醇调节元件结合蛋白-1c(SREBP-1c)水平显著降低,但过氧化物酶体增殖物激活受体α(PPARα)水平增加。这导致了脂质状况的改善,并减少了肝脏炎症、氧化应激和细胞凋亡指数。总之,我们的研究得出结论,BA可以通过调节NOX/p38 MAPK/PPARα通路和miR-155的表达来预防乙醇诱导的肝损伤。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Regulation of NOX/p38 MAPK/PPARα pathways and miR-155 expression by boswellic acids reduces hepatic injury in experimentally-induced alcoholic liver disease mouse model: novel mechanistic insight

Regulation of NOX/p38 MAPK/PPARα pathways and miR-155 expression by boswellic acids reduces hepatic injury in experimentally-induced alcoholic liver disease mouse model: novel mechanistic insight

Alcoholic liver disease (ALD) refers to hepatic ailments induced by excessive alcohol intake. The pathogenesis of ALD comprises a complex interplay between various mechanistic pathways, among which inflammation and oxidative stress are key players. Boswellic acids (BAs), found in Boswellia serrata, have shown hepatoprotective effects owing to their antioxidant and anti-inflammatory activities, nevertheless, their therapeutic potential against ALD has not been previously investigated. Hence, this study was performed to depict the possible protective effect of BAs and detect their underlying mechanism of action in an experimentally-induced ALD mouse model. Male BALB/c mice were equally categorized into six groups: control, BAs-treated, ALD, and ALD that received BAs at three-dose levels (125, 250, and 500 mg/kg) by oral gavage for 14 days. Results showed that the high dose of BAs had the most protective impact against ALD according to histopathology examination, blood alcohol concentration (BAC), and liver function enzymes. Mechanistic investigations revealed that BAs (500 mg/kg) caused a significant decrease in cytochrome P450 2E1(CYP2E1), nicotine adenine dinucleotide phosphate oxidase (NOX) 1/2/4, p38 mitogen-activated protein kinase (MAPK), and sterol regulatory element-binding protein-1c (SREBP-1c) levels, and the expression of miR-155, yet increased peroxisome proliferator-activated receptor alpha (PPARα) levels. This led to an improvement in lipid profile and reduced hepatic inflammation, oxidative stress, and apoptosis indices. In summary, our study concludes that BAs can protect against ethanol-induced hepatic injury, via modulating NOX/p38 MAPK/PPARα pathways and miR-155 expression.

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来源期刊
CiteScore
13.40
自引率
9.00%
发文量
48
审稿时长
3.3 months
期刊介绍: Archives of Pharmacal Research is the official journal of the Pharmaceutical Society of Korea and has been published since 1976. Archives of Pharmacal Research is an interdisciplinary journal devoted to the publication of original scientific research papers and reviews in the fields of drug discovery, drug development, and drug actions with a view to providing fundamental and novel information on drugs and drug candidates.
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