Glycyrrhizic acid (GA) and Sirtuin3 (Sirt3) were both found to be involved in epilepsy (EP), but their interaction was rarely studied. Herein, we aim to investigate the underlying mechanism of GA with the interaction of Sirt3 in juvenile EP rats. The EP model in juvenile rats was established by lithium chloride-pilocarpine and treated with different concentrations of GA, GA + DMSO or GA + 3-TYP [a selective inhibitor of Sirtuin3 (Sirt3)]. The expression of Sirt3, mitochondrial autophagy-related genes (C-III core 1, COX IV, LC3-I, LC3-II), apoptosis-related genes (Bcl-2, Bax, Caspase-3), glutathione (GSH), superoxide dismutase (SOD), malondialchehyche (MDA) and reactive oxygen species (ROS) as well as mitochondrial membrane potential were subsequently detected. The juvenile EP rats treated with GA showed increased level of C-III core 1 and COX IV, increased LC3-I/LC3-II, GSH and SOD, decreased MDA, increased expression of Sirt3, and Bcl-2, and decreased expression of Bax and Caspase-3. However, inhibition of Sirt3 caused reverse results. Collectively, GA could alleviate hippocampal pathological damage, promote mitochondrial autophagy and reduce oxidative stress in juvenile EP rats through activation of Sirt3. Understanding of these mechanisms may allow devising of novel therapeutics for pediatric EP.

甘草酸 (GA) 和 Sirtuin3 (Sirt3) 都被发现与癫痫 (EP) 相关，但很少研究它们的相互作用。在此，我们旨在研究 GA 与 Sirt3 在幼年 EP 大鼠中相互作用的潜在机制。用氯化锂-毛果芸香碱建立幼鼠EP模型，并用不同浓度的GA、GA+DMSO或GA+3-TYP[Sirtuin3的选择性抑制剂(Sirt3)]处理。Sirt3、线粒体自噬相关基因（C-III core 1、COX IV、LC3-I、LC3-II）、凋亡相关基因（Bcl-2、Bax、Caspase-3）、谷胱甘肽（GSH）、随后检测到超氧化物歧化酶 (SOD)、丙二醛 (MDA) 和活性氧 (ROS) 以及线粒体膜电位。用 GA 治疗的幼年 EP 大鼠显示 C-III 核心 1 和 COX IV 水平升高，LC3-I/LC3-II、GSH 和 SOD 增加，MDA 减少，Sirt3 和 Bcl-2 表达增加，Bax 和 Caspase-3 表达减少。然而，Sirt3 的抑制导致相反的结果。总的来说，GA可以通过激活Sirt3来减轻EP幼鼠海马病理损伤、促进线粒体自噬和减少氧化应激。了解这些机制可能有助于为小儿 EP 设计新的治疗方法。