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柚皮素对 2 型糖尿病诱导大鼠记忆功能障碍的保护作用中抗氧化和胆碱能系统的参与。

Participation of antioxidant and cholinergic system in protective effect of naringenin against type-2 diabetes-induced memory dysfunction in rats.

机构信息

Sinhgad College of Pharmacy, Post-Graduate Research Department, Off Sinhgad Road, Vadgaon (Bk), Pune 411 041, Maharashtra, India.

出版信息

Neuroscience. 2012 Dec 13;226:62-72. doi: 10.1016/j.neuroscience.2012.09.026. Epub 2012 Sep 19.

DOI:10.1016/j.neuroscience.2012.09.026
PMID:22999973
Abstract

Naringenin is a flavone flavonoid possessing antidiabetic, antioxidant and memory improving effects. Therefore, we studied the influence of naringenin against type-2 diabetes-induced memory dysfunction in rats. Type-2 diabetes was induced by high-fat diet and high-fat emulsion for two weeks and a low dose of streptozotocin (35 mg/kg). The memory deficit was assessed by using a novel object recognition paradigm. The changes in oxidative markers and cholinesterase (ChE) levels were evaluated in the hippocampal region. After confirmation of diabetes, naringenin (50mg/kg) treatment was given to animals as a preventive and in another set of experiments naringenin (25 and 50mg/kg) or pioglitazone (5mg/kg) or donepezil (3mg/kg) treatments were started after long-standing diabetes (4 weeks after confirmation). Both the treatment schedules show significant protection and improvement in cognitive behavior against diabetes-induced memory dysfunction and biochemical changes. Also, treatment with pioglitazone and donepezil improved memory performance in rats. Naringenin was found to decrease oxidative stress by depleting elevated lipid peroxide and nitric oxide and elevating reduced glutathione levels. Cholinergic function was improved by naringenin through the inhibition of elevated ChE activity. In conclusion, the present study suggests that naringenin acts as an antioxidant and ChE inhibitor against type-2 diabetes-induced memory dysfunction.

摘要

柚皮素是一种类黄酮类化合物,具有降血糖、抗氧化和改善记忆的作用。因此,我们研究了柚皮素对 2 型糖尿病大鼠记忆功能障碍的影响。2 型糖尿病由高脂肪饮食和高脂肪乳剂诱导两周,并用低剂量链脲佐菌素(35mg/kg)诱导。通过新物体识别范式评估记忆缺陷。评估海马区氧化标志物和胆碱酯酶(ChE)水平的变化。在确认糖尿病后,柚皮素(50mg/kg)作为预防措施给予动物,在另一组实验中,在长期糖尿病(确诊后 4 周)后开始给予柚皮素(25 和 50mg/kg)或吡格列酮(5mg/kg)或多奈哌齐(3mg/kg)治疗。这两种治疗方案都能显著改善认知行为,预防糖尿病引起的记忆功能障碍和生化变化。此外,吡格列酮和多奈哌齐治疗可改善大鼠的记忆表现。柚皮素通过消耗升高的脂质过氧化物和一氧化氮并升高还原型谷胱甘肽水平来减轻氧化应激。通过抑制升高的 ChE 活性,柚皮素改善了胆碱能功能。总之,本研究表明,柚皮素作为一种抗氧化剂和 ChE 抑制剂,可对抗 2 型糖尿病引起的记忆功能障碍。

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