Agnihotri College of Pharmacy, Pharmacology Division, Bapuji Wadi, Sindhi (Meghe), Wardha 442 001, Maharashtra, India.
Behav Brain Res. 2011 Jun 20;220(1):30-41. doi: 10.1016/j.bbr.2011.01.022. Epub 2011 Jan 22.
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 (25-100mg/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 (100mg/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.
链脲佐菌素诱导的大鼠记忆障碍是中枢神经系统变化的结果，这些变化继发于慢性高血糖、氧化应激损伤、胆碱能功能障碍和胰高血糖素样肽(GLP)改变。据报道，用降血糖药、抗氧化剂和胆碱能激动剂治疗可在该模型中产生有益的效果。小檗碱是一种异喹啉生物碱，具有抗糖尿病和抗氧化作用，可抑制乙酰胆碱酯酶（AChE），并增加 GLP 的释放。然而，目前尚无关于小檗碱对链脲佐菌素诱导的记忆障碍影响的报道。因此，我们使用 Morris 水迷宫范式测试了它对链脲佐菌素诱导的糖尿病大鼠认知功能障碍的影响。在大脑皮层和海马中评估了脂质过氧化和谷胱甘肽水平作为氧化应激参数，以及胆碱酯酶（ChE）活性作为胆碱能功能的标志物。糖尿病诱导 30 天后，大鼠表现出严重的学习和记忆缺陷，伴有脂质过氧化增加、还原型谷胱甘肽减少和 ChE 活性升高。相比之下，小檗碱（25-100mg/kg，po，每天两次，30 天）的慢性治疗改善了糖尿病大鼠的认知表现，降低了高血糖、氧化应激和 ChE 活性。在另一组实验中，在训练试验中小檗碱（100mg/kg）治疗也改善了学习和记忆，降低了高血糖、氧化应激和 ChE 活性。在训练试验中，慢性治疗（30 天）维生素 C 或二甲双胍和多奈哌齐也改善了糖尿病引起的记忆障碍，并降低了氧化应激和/或胆碱酯酶活性。总之，本研究表明，小檗碱治疗可防止糖尿病大鼠氧化应激和 ChE 活性的改变，从而防止记忆障碍。
