Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Sri Shivarathreeshwara Nagara, Mysuru 570015, Karnataka, India.
Neuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia.
Life Sci. 2019 Sep 15;233:116686. doi: 10.1016/j.lfs.2019.116686. Epub 2019 Jul 23.
Epilepsy is a neurological disorder characterized by an enduring predisposition to generate and aggravate epileptic seizures affecting around 1% of global population making it a serious health concern. Despite the recent advances in epilepsy research, no disease-modifying treatment able to terminate epileptogenesis have been reported yet reflecting the complexity in understanding the disease pathogenesis. To overcome the current treatment gap against epilepsy, one effective approach is to explore anti-epileptic effects from a drug that are approved to treat non-epileptic diseases. In this regard, Metformin emerged as an ideal candidate which is a first line treatment option for type 2 diabetes mellitus (T2DM), has conferred neuroprotection in several in vivo neurological disorders such as Alzheimer's diseases (AD), Parkinson's disease (PD), Stroke, Huntington's diseases (HD) including epilepsy. In addition, Metformin has ameliorated cognitive alteration, learning and memory induced by epilepsy as well as in animal model of AD. Herein, we review the promising findings demonstrated upon Metformin treatment against animal model of epilepsy however, the precise underlying mechanism of anti-epileptic potential of Metformin is not well understood. However, there is a growing understanding that Metformin demonstrates its anti-epileptic effect mainly via ameliorating brain oxidative damage, activation of AMPK, inhibition of mTOR pathway, downregulation of α-synuclein, reducing apoptosis, downregulation of BDNF and TrkB level. These reflects that Metformin being non-anti-epileptic drug (AED) has a potential to ameliorate the cellular pathways that were impaired in epilepsy reflecting its therapeutical potential against epileptic seizure that might plausibly overcome the limitations of today epilepsy treatment.
癫痫是一种以持久倾向产生和加重癫痫发作为特征的神经障碍，影响着全球约 1%的人口，因此成为一个严重的健康问题。尽管癫痫研究最近取得了进展，但尚未报道任何能够终止癫痫发生的疾病修饰治疗方法，这反映了理解疾病发病机制的复杂性。为了克服目前治疗癫痫的差距，一种有效的方法是从已被批准用于治疗非癫痫疾病的药物中探索抗癫痫作用。在这方面，二甲双胍作为一种理想的候选药物脱颖而出，它是治疗 2 型糖尿病（T2DM）的一线治疗选择，在阿尔茨海默病（AD）、帕金森病（PD）、中风、亨廷顿病（HD）等几种体内神经退行性疾病中具有神经保护作用，包括癫痫。此外，二甲双胍改善了癫痫以及 AD 动物模型引起的认知改变、学习和记忆。本文综述了二甲双胍治疗癫痫动物模型的有前途的研究结果，但二甲双胍抗癫痫作用的确切潜在机制尚不清楚。然而，人们越来越认识到，二甲双胍主要通过改善大脑氧化损伤、激活 AMPK、抑制 mTOR 通路、下调α-突触核蛋白、减少细胞凋亡、下调 BDNF 和 TrkB 水平来发挥其抗癫痫作用。这表明，作为非抗癫痫药物（AED）的二甲双胍有可能改善在癫痫中受损的细胞通路，反映了其针对癫痫发作的治疗潜力，可能克服目前癫痫治疗的局限性。
