Cancer Nanomedicine Laboratory, Department of Zoology, School of Life Sciences, Periyar University, Salem, Tamil Nadu, 636 011, India.
Department of Zoology, Periyar University, Salem, Tamil Nadu, 636 011, India.
Inflammopharmacology. 2023 Oct;31(5):2751-2771. doi: 10.1007/s10787-023-01313-x. Epub 2023 Sep 4.
Alzheimer's disease (AD) is an age-dependent neurodegenerative disease hallmarked by Amyloid-β (Aβ) aggregation, cognitive impairment, and neuronal and synaptic loss. In this study, AD was induced in male Wistar rats (n = 6) by the administration of intracerebroventricular-streptozotocin (ICV-STZ-3 mg/kg/day), and Voglibose (Vog) was administered at various doses (10, 25, and 50 mg/kg), while Galantamine (3 mg/kg) acted as a reference standard drug. Behavioral alterations in both spatial and non-spatial memory functions were evaluated in the experimental rats. At the end of the study, all experimental rats were sacrificed, and their brain parts, the cortex and hippocampus, were subjected to biochemical, western blot, and histopathological analysis. In our study results, the statistically significant dose-dependent results from the behavioral tests show the Voglibose-treated groups significantly improved (p < 0.0001) spatial and non-spatial memory functions when compared with ICV-STZ-treated group. Meanwhile, when compared with ICV-STZ-treated rats, treatment with Voglibose (10, 25, and 50 mg/kg) showed the activities of both acetylcholinesterase (AChE) and malondialdehyde (MDA) were significantly attenuated (p < 0.0001), while the operation of antioxidant enzymes was considerably enhanced (p < 0.0001). The molecular estimation showed that it significantly attenuates (p < 0.0001) the TNF-α, IL-1β, and CRP activity, and the western blot results demonstrate the significantly attenuated Aβ aggregation. The histopathological results showed that the Voglibose treatment had an effective improvement in clear cytoplasm and healthy neuronal cells. In conclusion, our results suggest that Voglibose has potent neuroprotective effects against the ICV-STZ-induced AD model. Furthermore, these results support the possibility of Voglibose as a therapeutic approach to improving cognitive function, suggesting that controlling Aβ aggregation might be a novel target for the development of AD.
阿尔茨海默病（AD）是一种与年龄相关的神经退行性疾病，其特征是淀粉样β（Aβ）聚集、认知障碍以及神经元和突触丢失。在这项研究中，雄性 Wistar 大鼠（n=6）通过侧脑室注射链脲佐菌素（ICV-STZ-3mg/kg/天）诱导 AD，并用不同剂量的伏格列波糖（Voglibose）（10、25 和 50mg/kg）进行治疗，而加兰他敏（3mg/kg）作为参考标准药物。在实验大鼠中评估了空间和非空间记忆功能的行为改变。在研究结束时，所有实验大鼠被处死，其大脑的皮质和海马部分进行了生化、western blot 和组织病理学分析。在我们的研究结果中，行为测试的统计学显著剂量依赖性结果表明，与 ICV-STZ 处理组相比，伏格列波糖治疗组显著改善了空间和非空间记忆功能（p<0.0001）。同时，与 ICV-STZ 处理的大鼠相比，伏格列波糖（10、25 和 50mg/kg）治疗组的乙酰胆碱酯酶（AChE）和丙二醛（MDA）活性显著减弱（p<0.0001），而抗氧化酶的活性则显著增强（p<0.0001）。分子估计表明，它显著减弱了（p<0.0001）TNF-α、IL-1β 和 CRP 活性，western blot 结果表明 Aβ 聚集得到了显著减弱。组织病理学结果表明，伏格列波糖治疗对细胞质清晰和健康神经元细胞有明显的改善作用。总之，我们的结果表明，伏格列波糖对 ICV-STZ 诱导的 AD 模型具有有效的神经保护作用。此外，这些结果支持了伏格列波糖作为改善认知功能的治疗方法的可能性，表明控制 Aβ 聚集可能是开发 AD 的一个新靶点。
