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水飞蓟素在小鼠急性束缚应激中的潜在抗抑郁样活性:对大脑皮质和海马中皮质酮及氧化应激反应的调节

Potential antidepressant-like activity of silymarin in the acute restraint stress in mice: Modulation of corticosterone and oxidative stress response in cerebral cortex and hippocampus.

作者信息

Thakare Vishnu N, Dhakane Valmik D, Patel Bhoomika M

机构信息

Department of Pharmacology, Sinhgad Institute of Pharmaceutical Sciences, Lonavala, 410401, Pune, Maharashtra, India; Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad 382 481, Gujarat, India.

Research and Development, Astec Life Sciences, Mumbai, Maharashtra, India.

出版信息

Pharmacol Rep. 2016 Oct;68(5):1020-7. doi: 10.1016/j.pharep.2016.06.002. Epub 2016 Jul 17.

Abstract

BACKGROUND

Silymarin is a polyphenolic flavanoid of Silybum marianum, elicited neuroprotection and antidepressant like activity in stressed model. It was found to increase 5-hydroxytryptamine (5-HT) levels in the cortex and dopamine (DA) and norepinephrine (NE) in the cerebellum in normal mice. The aim of the present study was to investigate the potential antidepressant-like activity of silymarin in the acute restraint stress (ARS) in mice.

METHODS

The ARS was induced by immobilizing the mice for a period of 7h using rodent restraint device preventing them for any physical movement. One hour prior to ARS, silymarin was administered at doses of 100mg/kg and 200mg/kg per oral to non stressed and ARS mice. Various behavioral parameters like immobility time in force swim test, locomotor activity in open field test, and biochemical alterations, serum corticosterone, 5-HT, DA, NE level, malondialdehyde (MDA), and antioxidant enzymes (GSH, CAT and SOD) in hippocampus and cerebral cortex in non stressed and ARS subjected mice were investigated.

RESULTS

Experimental findings reveals mice subjected to ARS exhibited significant increase immobility time, serum corticosterone, MDA formation and impaired SOD and CAT activities in hippocampus and cerebral cortex as compared to non stressed mice. Silymarin treatment (100mg/kg and 200mg/kg) significantly attenuated immobility time, corticosterone and restored the antioxidant enzymes after ARS.

CONCLUSION

The present experimental findings indicate that silymarin exhibits antidepressant like activity probably either through alleviating oxidative stress by modulation of corticosterone response, and antioxidant defense system in hippocampus and cerebral cortex in ARS mice.

摘要

背景

水飞蓟素是水飞蓟中的一种多酚类黄酮,在应激模型中具有神经保护和抗抑郁样活性。研究发现,它能提高正常小鼠皮质中的5-羟色胺(5-HT)水平以及小脑中的多巴胺(DA)和去甲肾上腺素(NE)水平。本研究旨在探讨水飞蓟素在小鼠急性束缚应激(ARS)中的潜在抗抑郁样活性。

方法

使用啮齿动物束缚装置将小鼠固定7小时以诱导ARS,防止其进行任何身体活动。在ARS前1小时,对未应激和ARS小鼠分别以100mg/kg和200mg/kg的剂量口服给予水飞蓟素。研究了各种行为参数,如强迫游泳试验中的不动时间、旷场试验中的运动活性,以及未应激和接受ARS处理的小鼠海马和大脑皮质中的生化改变、血清皮质酮、5-HT、DA、NE水平、丙二醛(MDA)和抗氧化酶(谷胱甘肽、过氧化氢酶和超氧化物歧化酶)。

结果

实验结果显示,与未应激小鼠相比,接受ARS处理的小鼠在海马和大脑皮质中的不动时间、血清皮质酮、MDA形成显著增加,超氧化物歧化酶和过氧化氢酶活性受损。水飞蓟素处理(100mg/kg和200mg/kg)显著缩短了ARS后的不动时间、降低了皮质酮水平,并恢复了抗氧化酶活性。

结论

目前的实验结果表明,水飞蓟素可能通过调节皮质酮反应减轻氧化应激,以及调节ARS小鼠海马和大脑皮质中的抗氧化防御系统,从而表现出抗抑郁样活性。

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