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烟酸对高脂肪饮食的保护作用:体内和体外研究。

Protective effects of niacin following high fat rich diet: an in-vivo and in-silico study.

机构信息

Department of Biochemistry, Faculty of Science, Bahauddin Zakariya University, Multan, 60800, Pakistan.

Department of Biochemistry, Faculty of Science, Science and Technology, Federal Urdu University of Arts, Karachi, 75270, Pakistan.

出版信息

Sci Rep. 2023 Dec 1;13(1):21343. doi: 10.1038/s41598-023-48566-8.

Abstract

Niacin had long been understood as an antioxidant. There were reports that high fat diet (HFD) may cause psychological and physical impairments. The present study was aimed to experience the effect of Niacin on % growth rate, cumulative food intake, motor activity and anxiety profile, redox status, 5-HT metabolism and brain histopathology in rats. Rats were administered with Niacin at a dose of 50 mg/ml/kg body weight for 4 weeks following normal diet (ND) and HFD. Behavioral tests were performed after 4 weeks. Animals were sacrificed to collect brain samples. Biochemical, neurochemical and histopathological studies were performed. HFD increased food intake and body weight. The exploratory activity was reduced and anxiety like behavior was observed in HFD treated animals. Activity of antioxidant enzymes was decreased while oxidative stress marker and serotonin metabolism in the brain of rat were increased in HFD treated animals than ND fed rats. Morphology of the brain was also altered by HFD administration. Conversely, Niacin treated animals decreased food intake and % growth rate, increased exploratory activity, produced anxiolytic effects, decreased oxidative stress and increased antioxidant enzyme and 5-HT levels following HFD. Morphology of brain is also normalized by the treatment of Niacin following HFD. In-silico studies showed that Niacin has a potential binding affinity with degradative enzyme of 5-HT i.e. monoamine oxidase (MAO) A and B with an energy of ~ - 4.5 and - 5.0 kcal/mol respectively. In conclusion, the present study showed that Niacin enhanced motor activity, produced anxiolytic effect, and reduced oxidative stress, appetite, growth rate, increased antioxidant enzymes and normalized serotonin system and brain morphology following HFD intake. In-silico studies suggested that increase 5-HT was associated with the binding of MAO with Niacin subsequentially an inhibition of the degradation of monoamine. It is suggested that Niacin has a great antioxidant potential and could be a good therapy for the treatment of HFD induced obesity.

摘要

烟酸长期以来一直被认为是一种抗氧化剂。有报道称,高脂肪饮食(HFD)可能导致心理和身体损伤。本研究旨在探讨烟酸对大鼠生长率%、累积食物摄入量、运动活性和焦虑特征、氧化还原状态、5-HT 代谢和脑组织病理学的影响。大鼠给予烟酸 50mg/ml/kg 体重,正常饮食(ND)和高脂肪饮食(HFD)后 4 周。4 周后进行行为测试。处死动物收集脑组织样本。进行生化、神经化学和组织病理学研究。HFD 增加了食物摄入量和体重。HFD 处理的动物探索性活动减少,表现出焦虑样行为。与 ND 喂养的大鼠相比,HFD 处理的大鼠大脑中的抗氧化酶活性降低,氧化应激标志物和 5-HT 代谢增加。HFD 给药还改变了大脑的形态。相反,烟酸处理的动物减少了食物摄入和生长率%,增加了探索性活动,产生了抗焦虑作用,降低了氧化应激,增加了抗氧化酶和 5-HT 水平,HFD 后。HFD 后烟酸治疗也使大脑形态正常化。计算机模拟研究表明,烟酸与 5-HT 的降解酶即单胺氧化酶(MAO)A 和 B 具有潜在的结合亲和力,结合能分别为~-4.5 和-5.0kcal/mol。总之,本研究表明,烟酸增强了运动活性,产生了抗焦虑作用,降低了氧化应激、食欲、生长率,增加了抗氧化酶,使 HFD 摄入后 5-HT 系统和大脑形态正常化。计算机模拟研究表明,5-HT 的增加与 MAO 与烟酸的结合有关,随后抑制单胺的降解。这表明烟酸具有很强的抗氧化潜力,可能是治疗 HFD 诱导肥胖的良好方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c679/10696033/a953217ba2e4/41598_2023_48566_Fig1_HTML.jpg

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