Division of Pharmacology, Institute of Pharmaceutical Research, GLA University, 281 406, Mathura, India.
Neurotox Res. 2021 Aug;39(4):1023-1043. doi: 10.1007/s12640-021-00336-y. Epub 2021 Feb 3.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with clinical manifestation of loss in cognitive functions in an individual. Though several drug candidates have been developed in the management of AD, an alternative option is still required due to serious adverse effects of the former. Recently, naringin exerts therapeutic benefits through rennin angiotensin system in experimental animals. However, its report on Mas receptor-mediated action against amyloid beta (Aβ)-induced mitochondrial dysfunction in AD-like animals is lacking. The experimental dementia was induced in the male rats by intracerebroventricular administration of Aβ on day 1 (D-1) of the experimental schedule of 14 days. Naringin treatment for 14 days attenuated Aβ-induced cognitive impairments of the animals in Morris water maze (MWM) and Y-maze tests. Further, naringin ameliorated the Aβ-induced cholinergic dysfunction in terms of decrease in the activity of choline acetyl transferase (ChAT) and level of acetylcholine (ACh) and increase in the activity of acetylcholine esterase (AChE) in rat hippocampus, prefrontal cortex, and amygdala. Furthermore, naringin attenuated Aβ-induced decrease in mitochondrial function, integrity, and bioenergetics in all the brain regions. Naringin also attenuated Aβ-induced increase in mitochondrial and cytosolic calcium level in all the brain regions. Moreover, naringin reversed Aβ-induced increase in apoptosis and level of mitochondrial calcium uniporter and decrease in the level of hemeoxygenase-1 in all the brain regions. On the contrary, A779 significantly abolished the therapeutic potential of naringin on Aβ-induced alteration in behavioral, biochemical, and molecular observations in these experimental animals. Thus, these observations indicate that naringin could be potential alternative in the management of AD.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其临床表现为个体认知功能丧失。尽管在 AD 的治疗中已经开发了几种候选药物，但由于前者的严重不良反应，仍需要替代方案。最近，柚皮苷通过肾素血管紧张素系统在实验动物中发挥治疗作用。然而，关于其对 AD 样动物中淀粉样β（Aβ）诱导的线粒体功能障碍的 Mas 受体介导作用的报道尚缺乏。在 14 天的实验方案的第 1 天（D-1），通过向雄性大鼠脑室内给予 Aβ诱导实验性痴呆。柚皮苷治疗 14 天可减轻 Aβ诱导的动物在 Morris 水迷宫（MWM）和 Y 迷宫测试中的认知障碍。此外，柚皮苷可改善 Aβ引起的胆碱能功能障碍，表现为大鼠海马、前额叶皮层和杏仁核中胆碱乙酰转移酶（ChAT）活性和乙酰胆碱（ACh）水平降低，乙酰胆碱酯酶（AChE）活性增加。此外，柚皮苷可减轻 Aβ诱导的所有脑区线粒体功能、完整性和生物能量学的降低。柚皮苷还可减轻 Aβ诱导的所有脑区线粒体和胞质钙水平升高。此外，柚皮苷可逆转 Aβ诱导的细胞凋亡和线粒体钙单向转运蛋白水平增加以及所有脑区血红素加氧酶-1水平降低。相反，A779 显著消除了柚皮苷对这些实验动物 Aβ诱导的行为、生化和分子改变的治疗潜力。因此，这些观察结果表明，柚皮苷可能是 AD 治疗的潜在替代药物。
