Protection of cholinergic and antioxidant system contributes to the effect of berberine ameliorating memory dysfunction in rat model of streptozotocin-induced diabetes
Protection of cholinergic and antioxidant system contributes to the effect of berberine ameliorating memory dysfunction in rat model of streptozotocin-induced diabetes
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DOI：
10.1016/j.bbr.2011.01.022
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发表时间：
2011-06-20
影响因子：
2.7
通讯作者：
Mundhada, Dharmendra
中科院分区：
文献类型：
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作者：
Bhutada, Pravinkumar;Mundhada, Yogita;Mundhada, Dharmendra
链脲佐菌素诱导的大鼠记忆障碍是继发于慢性高血糖、氧化应激受损、胆碱能功能障碍和胰高血糖素样肽（GLP）变化的CNS变化的结果。据报道，抗高血糖药、抗氧化剂和胆碱能激动剂治疗在该模型中产生有益作用。小檗碱是一种异喹啉生物碱，据报道具有抗糖尿病和抗氧化作用，乙酰胆碱酯酶（AChE）抑制剂，并增加GLP释放。但小檗碱对链脲佐菌素所致记忆障碍的影响尚未见报道。因此，我们采用Morris水迷宫实验范式，检测其对链脲佐菌素诱导的糖尿病大鼠认知功能障碍的影响。脂质过氧化和谷胱甘肽水平作为氧化应激的参数和胆碱酯酶（ChE）活性作为胆碱能功能的标志物进行了评估，在大脑皮层和海马。糖尿病诱导后30天，大鼠表现出严重的学习和记忆缺陷，与脂质过氧化增加，还原型谷胱甘肽减少，胆碱酯酶活性升高。相比之下，用小檗碱（25-100 mg/kg，口服，每日两次，30天）改善糖尿病大鼠的认知能力，降低高血糖、氧化应激和胆碱酯酶活性。在另一组实验中，训练试验期间的小檗碱（100 mg/kg）治疗也改善了学习和记忆，降低了高血糖症，氧化应激和胆碱酯酶活性。在训练试验期间用维生素C或二甲双胍和多奈哌齐进行慢性治疗（30天）也改善了糖尿病诱导的记忆障碍，并降低了氧化应激和/或胆碱酯酶活性。总之，本研究表明，黄连素治疗预防氧化应激和胆碱酯酶活性的变化，从而在糖尿病大鼠记忆障碍。(C)2011 Elsevier BM. All rights reserved.
Memory impairment induced by streptozotocin in rats is a consequence of changes in CNS that are secondary to chronic hyperglycemia, impaired oxidative stress, cholinergic dysfunction, and changes in glucagon-like peptide (GLP). Treatment with antihyperglycemics, antioxidants, and cholinergic agonists are reported to produce beneficial effect in this model. Berberine, an isoquinoline alkaloid is reported to exhibit anti-diabetic and antioxidant effect, acetylcholinesterase (AChE) inhibitor, and increases GLP release. However, no report is available on influence of berberine on streptozotocin-induced memory impairment. Therefore, we tested its influence against cognitive dysfunction in streptozotocin-induced diabetic rats using Morris water maze paradigm. Lipid peroxidation and glutathione levels as parameters of oxidative stress and choline esterase (ChE) activity as marker of cholinergic function were assessed in the cerebral cortex and hippocampus. Thirty days after diabetes induction rats showed a severe deficit in learning and memory associated with increased lipid peroxidation, decreased reduced glutathione, and elevated ChE activity. In contrast, chronic treatment with berberine (25-100 mg/kg, p.o., twice daily, 30 days) improved cognitive performance, lowered hyperglycemia, oxidative stress, and ChE activity in diabetic rats. In another set of experiment, berberine (100 mg/kg) treatment during training trials also improved learning and memory, lowered hyperglycemia, oxidative stress, and ChE activity. Chronic treatment (30 days) with vitamin C or metformin, and donepezil during training trials also improved diabetes-induced memory impairment and reduced oxidative stress and/or choline esterase activity. In conclusion, the present study demonstrates treatment with berberine prevents the changes in oxidative stress and ChE activity, and consequently memory impairment in diabetic rats. (C) 2011 Elsevier BM. All rights reserved.