Scholarlink

<p>Epilepsy is generally described as a pathology resulting from an imbalance between excitatory and inhibitory activities. In recent years, neurotrophins have been recognized as key players in the pathophysiology of nervous system diseases. One such neurotrophin, BDNF, and its receptor, TrkB, play critical roles as epileptogenic factors that regulate neuronal hyperexcitability and synaptic plasticity. In this study, we sought to elucidate the exact mechanisms underlying the neuroprotective and antiepileptic effects of pantoprazole. The molecular docking study indicated key interactions of pantoprazole with the TrkB receptor (PDB ID: 4AT3). Furthermore, pantoprazole exhibited notable in vitro TrkB kinase inhibitory activity (IC<sub>50</sub> = 24.01&#xa0;nM) and good cell viability (% viability = 0.0625&#xa0;mg/ml) against SH-SY5Y cells. Additionally, the protective effects of pantoprazole were assessed in a total oxidative status study, in which PTZ-induced oxidative stress was reduced by ~ 60%. Subsequent observations in the PTZ-induced epilepsy mouse model demonstrated that pantoprazole (5&#xa0;mg/kg and 10&#xa0;mg/kg; <i>p.o.</i>; OD) suppresses seizure severity and anxiety-like behavior while enhancing working memory in a dose-dependent manner. Furthermore, a significant increase in antioxidant enzymes such as catalase, reduced glutathione (GSH), and DNA levels, along with degradation of by-products of lipid peroxidation, malondialdehyde (MDA), nitric oxide, and myeloperoxidase (MPO), responsible for causing oxidative stress during epilepsy, occurred after pantoprazole treatment in the PTZ model. The therapy with pantoprazole also increased the mRNA expression of downregulated KCC2 and thereby restored GABAergic inhibition in the synapse and suppressed epilepsy. Together, these findings indicate that pantoprazole exhibits promising neuroprotective and antiepileptic effects via modulation of the TrkB/BDNF pathway and warrant further exploration in clinical subjects for its translation.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

From gastric to neuroprotection: pantoprazole mitigates epilepsy via TrkB/BDNF and KCC2 modulation

  • 期刊论文

  • 发表日期：

    2026年3月24日

查看全文
  • Arya Kuhu Vishwapriya,
  • Kamini Verma,
  • Garima Sharma,
  • Nitika Sindhu,
  • Swati Paliwal,
  • Smita Jain,
  • Jaya Dwivedi,
  • Sarvesh Paliwal,
  • Swapnil Sharma

摘要

Epilepsy is generally described as a pathology resulting from an imbalance between excitatory and inhibitory activities. In recent years, neurotrophins have been recognized as key players in the pathophysiology of nervous system diseases. One such neurotrophin, BDNF, and its receptor, TrkB, play critical roles as epileptogenic factors that regulate neuronal hyperexcitability and synaptic plasticity. In this study, we sought to elucidate the exact mechanisms underlying the neuroprotective and antiepileptic effects of pantoprazole. The molecular docking study indicated key interactions of pantoprazole with the TrkB receptor (PDB ID: 4AT3). Furthermore, pantoprazole exhibited notable in vitro TrkB kinase inhibitory activity (IC50 = 24.01 nM) and good cell viability (% viability = 0.0625 mg/ml) against SH-SY5Y cells. Additionally, the protective effects of pantoprazole were assessed in a total oxidative status study, in which PTZ-induced oxidative stress was reduced by ~ 60%. Subsequent observations in the PTZ-induced epilepsy mouse model demonstrated that pantoprazole (5 mg/kg and 10 mg/kg; p.o.; OD) suppresses seizure severity and anxiety-like behavior while enhancing working memory in a dose-dependent manner. Furthermore, a significant increase in antioxidant enzymes such as catalase, reduced glutathione (GSH), and DNA levels, along with degradation of by-products of lipid peroxidation, malondialdehyde (MDA), nitric oxide, and myeloperoxidase (MPO), responsible for causing oxidative stress during epilepsy, occurred after pantoprazole treatment in the PTZ model. The therapy with pantoprazole also increased the mRNA expression of downregulated KCC2 and thereby restored GABAergic inhibition in the synapse and suppressed epilepsy. Together, these findings indicate that pantoprazole exhibits promising neuroprotective and antiepileptic effects via modulation of the TrkB/BDNF pathway and warrant further exploration in clinical subjects for its translation.

Graphical Abstract