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Evaluation of Insulin Resistance Induced Brain Tissue Dysfunction in Obese Dams and their Neonates: Role of Ipriflavone Amelioration
Combinatorial Chemistry & High Throughput Screening ( IF 1.6 ) Pub Date : 2021-06-30 , DOI: 10.2174/1386207323666200808181148
Rania A Gad 1 , Eman S Abdel-Reheim 2 , Gaber M G Shehab 3 , Hani S Hafez 4 , Abdelaziz S A Abuelsaad 5
Affiliation  

Background: Nonalcoholic steatohepatitis (NASH) is associated with activation of liver fibrogenesis and predisposes to cirrhosis and associated morbi-mortality. A high fat high cholesterol diet (HFD) was provided to female albino rats to establish a NASH model. It is well known that the offspring of obese mothers have an increased risk of obesity and diabetes. The present study aimed at evaluating the ameliorative effects of ipriflavone (IP) as a natural food supplement on lipid metabolism, improving insulin sensitivity, reducing oxidative stress and inflammation, modifying metabolic risk factors and/or reduce brain damage, in both neonates and their dams.

Materials and Methods: The present aim was achieved by evaluating the oxidative stress and antioxidant defense system biomarkers, as thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH), catalase, and superoxide dismutase (SOD) activities. In addition, the neurotransmitter acetylcholine (Ach) and acetylcholine esterase (AchE) activities, as well as levels of the apolipoprotein E4 (APOE4); β-secretase, hyper phosphor-tau and β-amyloid 42; 3-hydroxy- 3-methyl glutaryl coenzyme A reductase (HMG CoA R)” and COX-II by immunoblotting assays in the brain tissue of neonates and their dams in all the studied groups.

Results: A very significant amelioration in acetylcholine and acetylcholine esterase neurotransmitters, Alzheimer’s makers (β-amyloid), antioxidants (reduced glutathione (GSH) contents, catalase (CAT) and superoxide dismutase (SOD); and inflammatory cytokines in NASH model is observed upon administrating ipriflavone (IP) as a natural food supplement. The multifunctional activities of ipriflavone as an antioxidant, anti-inflammatory and anti-insulin resistance drug were discussed and correlated with other investigations.

Conclusion: Regarding steatohepatitis, the present study confirmed the anti-inflammatory effects of the ipriflavone (IP). Therefore, future studies should focus on hepatic fatty acid uptake, hepatic lipogenesis, and fatty acid oxidation and the role of IP in regulating hepatic fat metabolism. In addition, natural products like IP could be combined with the highly used pharmaceutical drugs to reduce the side effects of nonalcoholic steatohepatitis, and minimize progression of dementia. Moreover, the present study supports further attempts to heal the neural dysfunction via antioxidant and anti-inflammatory cascade activities using ipriflavone (IP).



中文翻译:

评估肥胖母猪及其新生儿的胰岛素抵抗引起的脑组织功能障碍:改善伊普黄酮的作用

背景:非酒精性脂肪性肝炎 (NASH) 与肝纤维化的激活有关,并易患肝硬化和相关的死亡率。为雌性白化大鼠提供高脂肪高胆固醇饮食(HFD)以建立 NASH 模型。众所周知,肥胖母亲的后代患肥胖症和糖尿病的风险增加。本研究旨在评估 ipriflavone (IP) 作为天然食品补充剂对脂质代谢的改善作用、改善胰岛素敏感性、减少氧化应激和炎症、改变代谢风险因素和/或减少新生儿及其母鼠的脑损伤.

材料和方法:本目标是通过评估氧化应激和抗氧化防御系统生物标志物来实现的,如硫代巴比妥酸反应物质 (TBARS) 和还原型谷胱甘肽 (GSH)、过氧化氢酶和超氧化物歧化酶 (SOD) 活性。此外,神经递质乙酰胆碱 (Ach) 和乙酰胆碱酯酶 (AchE) 的活性,以及​​载脂蛋白 E4 (APOE4) 的水平;β-分泌酶、高磷-tau 蛋白和 β-淀粉样蛋白 42;3-羟基-3-甲基戊二酰辅酶 A 还原酶 (HMG CoA R)”和 COX-II 通过在所有研究组的新生儿及其母畜的脑组织中进行免疫印迹分析。

结果:乙酰胆碱和乙酰胆碱酯酶神经递质、阿尔茨海默氏症制造商(β-淀粉样蛋白)、抗氧化剂(降低的谷胱甘肽 (GSH) 含量、过氧化氢酶 (CAT) 和超氧化物歧化酶 (SOD);以及 NASH 模型中的炎性细胞因子)的显着改善ipriflavone (IP) 作为天然食品补充剂给药 ipriflavone 作为抗氧化、抗炎和抗胰岛素抵抗药物的多功能活性进行了讨论,并与其他研究相关联。

结论:关于脂肪性肝炎,本研究证实了伊普黄酮 (IP) 的抗炎作用。因此,未来的研究应侧重于肝脏脂肪酸摄取、肝脏脂肪生成和脂肪酸氧化以及 IP 在调节肝脏脂肪代谢中的作用。此外,IP 等天然产物可以与高度使用的药物结合,以减少非酒精性脂肪性肝炎的副作用,并最大程度地减少痴呆症的进展。此外,本研究支持进一步尝试使用 ipriflavone (IP) 通过抗氧化和抗炎级联活动治愈神经功能障碍。

更新日期:2021-06-01
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