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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Inflammation Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1530735
This article is part of the Research Topic Targeted Drug Delivery and Mode of Action of Small Molecules in Neuroinflammation View all articles

Glycyrrhizin as a Potential Disease-Modifying Therapy for Epilepsy: Insights into Targeting Pyroptosis to Exert Neuroprotective and Anticonvulsant Effects

Provisionally accepted
Lei Wei Lei Wei Sijie Ou Sijie Ou Youshi Meng Youshi Meng Lanfeng Sun Lanfeng Sun Lin Zhang Lin Zhang Yuling Lu Yuling Lu *Yuan Wu Yuan Wu *
  • Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China, Nanning, China

The final, formatted version of the article will be published soon.

    Background: For patients with epilepsy, antiseizure medication remains the primary treatment; however, it is ineffective in approximately 30% of cases. These patients experience progressive neuronal damage and poor outcomes. Therefore, there is an urgent need for disease-modifying therapy (DMT) that targets the pathogenesis of epilepsy. Glycyrrhizin has shown potential as a DMT in epilepsy due to its multiple targets and diverse mechanisms. Previous studies suggest that glycyrrhizin may regulate key processes involved in epilepsy pathogenesis, such as neuroinflammation and cell death, but its effects on pyroptosis have not been reported. Methods: This study employed bioinformatics techniques to identify potential molecular targets for glycyrrhizin in epilepsy treatment and then validated using a kainic acid-induced status epilepticus mouse model. Results: Glycyrrhizin treatment significantly prolonged seizure latency, reduced seizure duration, and alleviated neuronal damage in the status epilepticus mouse model. Molecular experiments indicated that glycyrrhizin may regulate pyroptosis through mediation of the high mobility group box 1 (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling pathway. Conclusion: Glycyrrhizin exerts neuroprotective and anticonvulsant effects in epilepsy by regulating pyroptosis via the HMGB1/TLR4/NF-κB signaling pathway, offering novel insights into its potential as a DMT for epilepsy.

    Keywords: Epilepsy, Glycyrrhizin, pyroptosis, disease-modifying therapy, Neuroinflammation

    Received: 19 Nov 2024; Accepted: 09 Dec 2024.

    Copyright: © 2024 Wei, Ou, Meng, Sun, Zhang, Lu and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Yuling Lu, Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China, Nanning, China
    Yuan Wu, Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China, Nanning, China

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