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白藜芦醇通过靶向肝细胞中的生物钟调节因子 Bmal1 和 Cry1 预防丙烯酰胺诱导的线粒体功能障碍和炎症反应。

Resveratrol Prevents Acrylamide-Induced Mitochondrial Dysfunction and Inflammatory Responses via Targeting Circadian Regulator Bmal1 and Cry1 in Hepatocytes.

机构信息

Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering , Northwest A&F University , Yangling 712100 , China.

出版信息

J Agric Food Chem. 2019 Aug 7;67(31):8510-8519. doi: 10.1021/acs.jafc.9b03368. Epub 2019 Jul 24.

DOI:10.1021/acs.jafc.9b03368
PMID:31294559
Abstract

Acrylamide, mainly formed in Maillard browning reaction during food processing, causes defects in liver circadian clock and mitochondrial function by inducing oxidative stress. Resveratrol is a polyphenol that has powerful antioxidant and anti-inflammatory activity. However, the preventive effects of resveratrol on acrylamide-triggered oxidative damage and circadian rhythm disorders are unclear at the current stage. The present research revealed that resveratrol pretreatment prevented acrylamide-induced cell death, mitochondrial dysfunction, and inflammatory responses in HepG2 liver cells. Acrylamide significantly triggered disorders of circadian genes transcription and protein expressions including Bmal1 and Cry 1 in primary hepatocytes, which were prevented by resveratrol pretreatment. Moreover, we found that the beneficial effects of resveratrol on stimulating Nrf2/NQO-1 pathway and mitochondrial respiration complex expressions in acrylamide-treated cells were Bmal1-dependent. Similarly, the inhibitory effects of resveratrol on inflammation signaling NF-κB were Cry1-dependent. In conclusion, these results demonstrated resveratrol could be a promising compound in suppressing acrylamide-induced hepatotoxicity and balancing the circadian clock.

摘要

丙烯酰胺主要在食品加工过程中的美拉德褐变反应中形成,通过诱导氧化应激引起肝脏生物钟和线粒体功能缺陷。白藜芦醇是一种具有强大抗氧化和抗炎活性的多酚。然而,白藜芦醇对丙烯酰胺引发的氧化损伤和昼夜节律紊乱的预防作用在现阶段尚不清楚。本研究表明,白藜芦醇预处理可防止丙烯酰胺诱导的 HepG2 肝细胞死亡、线粒体功能障碍和炎症反应。丙烯酰胺显著触发了原代肝细胞中昼夜节律基因转录和蛋白表达的紊乱,包括 Bmal1 和 Cry 1,而白藜芦醇预处理可预防这种紊乱。此外,我们发现白藜芦醇对刺激丙烯酰胺处理细胞中 Nrf2/NQO-1 通路和线粒体呼吸复合物表达的有益作用依赖于 Bmal1。同样,白藜芦醇对炎症信号 NF-κB 的抑制作用依赖于 Cry1。总之,这些结果表明白藜芦醇可能是一种有前途的化合物,可抑制丙烯酰胺诱导的肝毒性并平衡生物钟。

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