Abdelaziz Heba A, Hamed Mohamed F, Ghoniem Hamdy A, Nader Manar A, Suddek Ghada M
Pharmacology and Biochemistry Department, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, 35712, Egypt.
Pharmacology and Toxicology Department, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
J Neuroimmune Pharmacol. 2025 Jan 7;20(1):5. doi: 10.1007/s11481-024-10162-6.
Empagliflozin (EMPA) is one of the sodium/glucose cotransporter 2 (SGLT2) inhibitors that has been recently approved for the treatment of diabetes mellitus type II. Recently, EMPA has shown protective effects in different neurological disorders, besides its antidiabetic activity. Kindling is a relevant model to study epilepsy and neuroplasticity. This study aimed to investigate the potential protective effects of EMPA (1 and 3 mg/kg orally) against convulsant effects induced by pentylenetetrazole (PTZ) using a modified window- (win-) PTZ kindling protocol. The biochemical dysfunction and hippocampal damage induced by PTZ were profoundly reversed by EMPA treatment in a dose-dependent manner, as evidenced by the significant increase in reduced glutathione (GSH) and decrease in malondialdehyde (MDA) hippocampal contents. Furthermore, EMPA counteracted PTZ-induced neuronal damage in the hippocampal region, as confirmed by histopathological examination of the hippocampal tissues. EMPA impaired astrocytosis and showed an antiapoptotic effect through a significant reduction of glial fibrillary acidic protein (GFAP) and BCL2-Associated X Protein (BAX) expressions, respectively. Interestingly, EMPA exhibited an antiepileptic effect against PTZ-induced seizures through significantly reducing neuronal PAS domain Protein 4 (Npas4), cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) hippocampal expressions, and enhancing the brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) pathway, which are found to be involved in epileptogenesis, eventually leading to significant improvement of behavioral impairments induced by PTZ. Hence, these results showed further prospective insights for EMPA as a neuroprotective agent.
恩格列净（EMPA）是一种钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂，最近已被批准用于治疗II型糖尿病。最近，EMPA除了具有抗糖尿病活性外，还在不同的神经疾病中显示出保护作用。点燃是一种用于研究癫痫和神经可塑性的相关模型。本研究旨在使用改良的窗口式（win-）戊四氮（PTZ）点燃方案，研究EMPA（口服1和3mg/kg）对PTZ诱导的惊厥作用的潜在保护作用。EMPA治疗以剂量依赖性方式显著逆转了PTZ诱导的生化功能障碍和海马损伤，海马组织中还原型谷胱甘肽（GSH）显著增加和丙二醛（MDA）含量降低证明了这一点。此外，海马组织的组织病理学检查证实，EMPA可对抗PTZ诱导的海马区神经元损伤。EMPA分别通过显著降低胶质纤维酸性蛋白（GFAP）和BCL2相关X蛋白（BAX）的表达，抑制星形细胞增生并显示出抗凋亡作用。有趣的是，EMPA通过显著降低神经元PAS结构域蛋白4（Npas4）、环磷酸腺苷（cAMP）反应元件结合蛋白（CREB）在海马中的表达，并增强脑源性神经营养因子（BDNF）-原肌球蛋白受体激酶B（TrkB）通路，从而对PTZ诱导的癫痫发作表现出抗癫痫作用，这些通路被发现与癫痫发生有关，最终导致PTZ诱导的行为障碍得到显著改善。因此，这些结果为EMPA作为一种神经保护剂提供了进一步的前瞻性见解。
