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柚皮苷通过抑制 Sirtuin1 缓解慢性睡眠剥夺诱导的疼痛。

Naringenin Ameliorates Chronic Sleep Deprivation-Induced Pain via Sirtuin1 Inhibition.

机构信息

Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, Panjab University, Sector 14, 160014, Chandigarh, India.

Food and Nutritional Biotechnology Laboratory, National Agri-Food Biotechnology Institute, SAS Nagar, 140306, Punjab, India.

出版信息

Neurochem Res. 2021 May;46(5):1177-1187. doi: 10.1007/s11064-021-03254-9. Epub 2021 Feb 18.

DOI:10.1007/s11064-021-03254-9
PMID:33599956
Abstract

Growing experimental evidences have suggested the reciprocal correlation between sleep deprivation and pain. Inflammation and oxidative stress are among the key pathways underlying this correlation. Therefore, the present study was aimed to assess the effect of antioxidant and anti-inflammatory compound naringenin (NGN) against chronic sleep deprivation (CSD)-induced mechanical and thermal hyperalgesia in female Swiss albino mice. In this study, mice were chronically sleep-deprived for 8 h a day for five days a week with the weekend as a free sleep period and continued for nine weeks using a modified multiple platform method. The pain behavioral tests were conducted at the end of the fourth week to assess the development of hyperalgesia followed by the administration of NGN and a combination of NGN with Sirtinol (SIR, a sirtuin1 inhibitor) till the end of the study. After nine weeks, pain behavioral tests, along with oxidative stress and inflammatory parameters in cortex and striatum, were assessed. Results indicated that CSD-induced hyperalgesia in mice accompanied by increased oxidative stress and inflammatory markers in cortex and striatum of the brain. NGN combatted the hyperalgesic response and also decreased levels of oxidative stress and inflammatory markers. Furthermore, the pharmacological effect of NGN was mitigated with SIR. Thus, the findings of the present study reveal that NGN is acting via sirtuin1 to exert its antinociceptive activity against CSD-induced hyperalgesia.

摘要

越来越多的实验证据表明,睡眠剥夺与疼痛之间存在相互关联。炎症和氧化应激是这种相关性的关键途径之一。因此,本研究旨在评估抗氧化和抗炎化合物柚皮素(NGN)对雌性瑞士白化小鼠慢性睡眠剥夺(CSD)引起的机械性和热痛觉过敏的影响。在这项研究中,使用改良的多平台方法,每天将小鼠慢性剥夺 8 小时睡眠,每周五天,周末为自由睡眠期,持续九周。在第四周结束时进行疼痛行为测试,以评估痛觉过敏的发展,然后给予 NGN 以及 NGN 与 Sirtinol(SIR,一种 Sirtuin1 抑制剂)的组合,直至研究结束。九周后,评估疼痛行为测试以及大脑皮层和纹状体中的氧化应激和炎症参数。结果表明,CSD 诱导的小鼠痛觉过敏伴随着大脑皮层和纹状体中氧化应激和炎症标志物的增加。NGN 对抗痛觉过敏反应,并降低氧化应激和炎症标志物的水平。此外,SIR 减轻了 NGN 的药理作用。因此,本研究的结果表明,NGN 通过 Sirtuin1 发挥其抗伤害感受活性,对抗 CSD 诱导的痛觉过敏。

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