University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Food Chem Toxicol. 2020 Nov;145:111684. doi: 10.1016/j.fct.2020.111684. Epub 2020 Aug 14.
In this study, the effect of Phycocyanin (Pc) to ameliorate the cognitive dysfunction in experimental model of Alzheimer's disease (AD) was evaluated. Intracerebroventricular (ICV) induction of Streptozotocin (STZ) (3 mg/kg) was done bilaterally twice in rats on alternative days. Rats were injected with Pc (50, 100 mg/kg; i. p.) for 28 days daily for behavioural and cholinergic activity assessment. As the effect was only significant at 100 mg/kg, later molecular experiments were performed using the same only. STZ induction led to increased activity of hippocampal cholinesterases and BAX and decreased activity of BCL-2 and ChAT. It enhanced TNF-α, and NF-κB in rat's brain and reduced BDNF and IGF-1 levels. Dysfunctional insulin signaling and decreased gene expressions of PI3-K, AKT was also observed. However, Pc treatment significantly prevented STZ-induced increased activity of hippocampal cholinesterases and BAX as well as increased the levels of BCL-2 and ChAT. Neuroinflammation was significantly attenuated and BDNF and IGF-1 levels were upregulated. Further, Pc also alleviated dysfunctional insulin signaling as evidenced by increased gene expression of IRS-1, PI3-K, AKT. In conclusion, our study demonstrated the immense potential of Pc in attenuating STZ-induced cognitive decline and it may be further explored as a therapeutic agent in managing AD.
在这项研究中，评估了藻蓝蛋白 (Pc) 改善阿尔茨海默病 (AD) 实验模型中认知功能障碍的效果。通过对大鼠双侧脑室 (ICV) 注射链脲佐菌素 (STZ) (3mg/kg)，隔一天注射两次。大鼠每天腹腔注射 Pc (50、100mg/kg) 28 天，用于行为和胆碱能活性评估。由于只有在 100mg/kg 时效果才显著，因此后来只使用相同剂量进行了分子实验。STZ 诱导导致海马胆碱酯酶和 BAX 的活性增加，而 BCL-2 和 ChAT 的活性降低。它增强了大鼠大脑中的 TNF-α 和 NF-κB，降低了 BDNF 和 IGF-1 水平。还观察到胰岛素信号传导功能障碍和 PI3-K、AKT 的基因表达减少。然而，Pc 处理可显著预防 STZ 诱导的海马胆碱酯酶和 BAX 活性增加，并增加 BCL-2 和 ChAT 的水平。神经炎症显著减轻，BDNF 和 IGF-1 水平上调。此外，Pc 还缓解了胰岛素信号传导功能障碍，IRS-1、PI3-K、AKT 的基因表达增加。总之，我们的研究表明 Pc 在减轻 STZ 诱导的认知下降方面具有巨大的潜力，可进一步探索作为治疗 AD 的治疗剂。
