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姜黄素和黄芩苷通过Nrf2/HO-1途径减轻乙醇诱导的肝脏氧化损伤。

Curcumin and Baicalin ameliorate ethanol-induced liver oxidative damage via the Nrf2/HO-1 pathway.

作者信息

Wang Xiaoxia, Chang Xuhong, Zhan Haibing, Zhang Qiong, Li Chengyun, Gao Qing, Yang Mengmeng, Luo Zhen, Li Sheng, Sun Yingbiao

机构信息

Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China.

School of Pharmacy, Lanzhou University, Lanzhou, China.

出版信息

J Food Biochem. 2020 Oct;44(10):e13425. doi: 10.1111/jfbc.13425. Epub 2020 Aug 8.

DOI:10.1111/jfbc.13425
PMID:32770697
Abstract

One of the key mechanisms of alcoholic liver disease is oxidative stress. Both Curcumin and Baicalin exert antioxidant effects, but the mechanism of their combined effects of ethanol-induced liver injury is still unclear. This study was conducted to evaluate the dual antioxidant activity of Curcumin combined with Baicalin against ethanol-induced liver injury in rats. Rats were divided into five groups, a control, ethanol, ethanol + Curcumin (50 mg/kg), ethanol + Baicalin (50 mg/kg), and ethanol + Curcumin +Baicalin group with ten rats per group. The effects of ethanol on liver enzymes, oxidative stress indicators and the levels of Nrf2/HO-1 pathway related proteins and mRNA were observed along with liver histopathology in rats. Our results found that the serum ALT and AKP levels were increased in ethanol-treated rats, which also showed a rising trend of 8-OHdG and LPO levels while hydroxyl radical scavenging ability, T-AOC, and the activities of SOD and GSH-Px were decreased in liver. The mRNA levels of Nrf2 and HO-1, the ratio of p-Nrf2/Nrf2, the protein level of HO-1 were decreased while NQO1 mRNA level, Nrf2, p-Nrf2, and NQO1 protein levels were increased in ethanol-treated rats. Combination treatment of Curcumin and Baicalin significantly reversed the ethanol-induced liver oxidative damage and further activate the Nrf2/HO-1 pathway, which was more effective than each drug alone. In conclusion, evidence has shown for the first time in this study that Curcumin combined with Baicalin ameliorated ethanol-induced liver oxidative damage in rats and revealed liver-protection. PRACTICAL APPLICATIONS: Many drugs for treating alcoholic liver disease are available commercially, but some adverse effects they have may cause secondary damage to the liver. At present, the combined treatment of different natural phytochemicals has attracted special attention in modern medicine. Curcumin, a kind of phytochemicals, is extracted from turmeric rhizome. Baicalin is one of the major active components of Scutellaria Baicalensis. The current research is to explore the antioxidant effect of Curcumin and Baicalin in ethanol-induced liver injury in rats. Our research proves that Curcumin combined with Baicalin on ethanol-induced liver oxidative damage is superior to single drug treatment. Therefore, the combination of Curcumin and Baicalin may provide a more prospective natural remedy to combat ethanol-induced liver injury.

摘要

酒精性肝病的关键机制之一是氧化应激。姜黄素和黄芩苷都具有抗氧化作用,但它们联合作用于乙醇诱导的肝损伤的机制仍不清楚。本研究旨在评估姜黄素与黄芩苷联合对大鼠乙醇诱导的肝损伤的双重抗氧化活性。将大鼠分为五组,即对照组、乙醇组、乙醇 + 姜黄素(50 mg/kg)组、乙醇 + 黄芩苷(50 mg/kg)组以及乙醇 + 姜黄素 + 黄芩苷组,每组10只大鼠。观察乙醇对大鼠肝脏酶、氧化应激指标以及Nrf2/HO-1通路相关蛋白和mRNA水平的影响,并进行肝脏组织病理学检查。我们的结果发现,乙醇处理的大鼠血清ALT和AKP水平升高,肝脏中8-OHdG和LPO水平也呈上升趋势,而羟自由基清除能力、总抗氧化能力以及SOD和GSH-Px的活性降低。乙醇处理的大鼠中,Nrf2和HO-1的mRNA水平、p-Nrf2/Nrf2比值、HO-1蛋白水平降低,而NQO1 mRNA水平、Nrf2、p-Nrf2和NQO1蛋白水平升高。姜黄素与黄芩苷联合治疗显著逆转了乙醇诱导的肝脏氧化损伤,并进一步激活了Nrf2/HO-1通路,其效果比单独使用每种药物更显著。总之,本研究首次证明姜黄素与黄芩苷联合可改善大鼠乙醇诱导的肝脏氧化损伤并具有肝脏保护作用。实际应用:许多治疗酒精性肝病的药物已在市场上销售,但它们的一些副作用可能会对肝脏造成继发性损害。目前,不同天然植物化学物质的联合治疗在现代医学中受到了特别关注。姜黄素是一种从姜黄根茎中提取的植物化学物质。黄芩苷是黄芩的主要活性成分之一。当前的研究旨在探索姜黄素和黄芩苷对大鼠乙醇诱导的肝损伤的抗氧化作用。我们的研究证明,姜黄素与黄芩苷联合对乙醇诱导的肝脏氧化损伤优于单一药物治疗。因此,姜黄素与黄芩苷联合可能为对抗乙醇诱导的肝损伤提供一种更具前景的天然疗法。

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