Jamshidnejad-Tosaramandani Tahereh, Kashanian Soheila, Babaei Mahsa, Al-Sabri Mohamed H, Schiöth Helgi B
Nanobiotechnology Department, Faculty of Innovative Science and Technology, Razi University, Kermanshah 6714414971, Iran.
Department of Biology, Faculty of Science, Razi University, Kermanshah 6714414971, Iran.
Pharmaceuticals (Basel). 2021 Nov 9;14(11):1136. doi: 10.3390/ph14111136.
There is no definite cure for Alzheimer's disease (AD) due to its multifactorial origin. Drugs that inhibit acetylcholinesterase (AChE), such as rivastigmine, are promising symptomatic treatments for AD. Emerging evidence suggests that insulin therapy can hinder several aspects of AD pathology. Insulin has been shown to modify the activity of AChE, but it is still unknown how insulin and AChE interact. Combination therapy, which targets several features of the disease based on existing medications, can provide a worthy therapy option for AD management. However, to date, no studies have examined the potential interaction of insulin with AChE and/or rivastigmine in vitro. In the present study, we employed the Response Surface Methodology (RSM) as an in vitro assessment to investigate the effect of insulin on both AChE activity and rivastigmine inhibitory action using a common spectrophotometric assay for cholinesterase activity, Ellman's method. Our results showed that insulin, even at high concentrations, has an insignificant effect on both the activity of AChE and rivastigmine's inhibitory action. The variance of our data is near zero, which means that the dispersion is negligible. However, to improve our understanding of the possible interaction of insulin and rivastigmine, or its target AChE, more in silico modelling and in vivo studies are needed.
由于阿尔茨海默病（AD）病因具有多因素性，因此目前尚无确切的治愈方法。抑制乙酰胆碱酯酶（AChE）的药物，如卡巴拉汀，是有前景的AD对症治疗药物。新出现的证据表明，胰岛素治疗可以在多个方面阻碍AD病理进程。胰岛素已被证明可改变AChE的活性，但胰岛素与AChE如何相互作用仍不清楚。基于现有药物针对疾病多个特征的联合治疗，可以为AD管理提供一个有价值的治疗选择。然而，迄今为止，尚无研究在体外检测胰岛素与AChE和/或卡巴拉汀之间的潜在相互作用。在本研究中，我们采用响应面法（RSM）作为体外评估方法，使用一种常用的胆碱酯酶活性分光光度测定法（埃尔曼法）来研究胰岛素对AChE活性和卡巴拉汀抑制作用的影响。我们的结果表明，即使在高浓度下，胰岛素对AChE活性和卡巴拉汀的抑制作用均无显著影响。我们数据的方差接近零，这意味着离散度可以忽略不计。然而，为了更好地理解胰岛素与卡巴拉汀或其靶标AChE之间可能的相互作用，还需要更多的计算机模拟和体内研究。
