Yu Dongsheng, Li Shuang, Li Xiaoping, Zhang Xiaodan, Guo Danfeng
Department of Chinese Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Front Nutr. 2025 Aug 13;12:1625533. doi: 10.3389/fnut.2025.1625533. eCollection 2025.
Xianyu capsule (XYC) is a commonly used traditional Chinese medicine in the clinical treatment of epilepsy, with significant curative effect and good safety. However, its mechanism of action remains poorly understood. This research employed a multi-omics approach to systematically evaluate the anti-epileptic efficacy of XYC and elucidate its underlying mechanisms.
Epilepsy rat model was established by lithium-pilocarpine hydrochloride injection. XYC was administered and the effects and mechanism was analyzed with H&E and Nissl staining, TUNEL assay, ELISA assay for inflammatory cytokines, 16S rDNA, non-targeted metabolomics and network pharmacology. The potential target were experimentally validated with RT-qPCR and Western blotting analysis.
XYC administration ameliorated the pathological changes and neurons apoptosis of brain hippocampus CA1 region, with reduced MDA and increased SOD and CAT levels in hippocampus, and decreased inflammation cytokine in serum. 16S rDNA sequencing revealed distinct gut microbial restructuring in XYC-treated epileptic models, characterized by phylum-level alterations in lipid-associated taxa (, , , ) and genus-level modulations (, , ). Serum metabolomics identified 149 differentially expressed metabolites positively correlated with XYC's anti-epileptic effects, predominantly enriched in glycerophospholipid metabolic pathways. Network pharmacology identified AKT1, INS, and IL-6 as pivotal mediators of XYC's therapeutic effects, which were subsequently validated with Western blotting and ELISA assay.
Our results proved that XYC exerted favorable effect on epilepsy by modulating the gut microbiota and serum lipid metabolic, especially neuroinflammation and glycerophospholipid metabolism by regulating the AKT1, INS and IL-6 expression levels. In addition, targeting neuroinflammatory pathways and modulating glycerophospholipid metabolism may represent a promising therapeutic strategy for epilepsy management.
痫愈胶囊（XYC）是临床治疗癫痫常用的中药，疗效显著且安全性良好。然而，其作用机制仍不清楚。本研究采用多组学方法系统评价痫愈胶囊的抗癫痫疗效并阐明其潜在机制。
通过注射氯化锂-匹罗卡品建立癫痫大鼠模型。给予痫愈胶囊，采用苏木精-伊红（H&E）染色、尼氏染色、TUNEL 检测、炎症细胞因子酶联免疫吸附测定（ELISA）、16S 核糖体 DNA（rDNA）、非靶向代谢组学和网络药理学分析其作用效果及机制。通过实时定量聚合酶链反应（RT-qPCR）和蛋白质免疫印迹分析对潜在靶点进行实验验证。
给予痫愈胶囊可改善脑海马 CA1 区的病理变化和神经元凋亡，降低海马丙二醛（MDA）水平，提高超氧化物歧化酶（SOD）和过氧化氢酶（CAT）水平，并降低血清炎症细胞因子水平。16S rDNA 测序显示，痫愈胶囊治疗的癫痫模型中肠道微生物群发生明显重构，特征为脂质相关分类群在门水平的改变（、、、）和属水平的调节（、、）。血清代谢组学鉴定出 149 种与痫愈胶囊抗癫痫作用呈正相关的差异表达代谢物，主要富集于甘油磷脂代谢途径。网络药理学确定 AKT1、胰岛素（INS）和白细胞介素-6（IL-6）是痫愈胶囊治疗作用的关键介质，随后通过蛋白质免疫印迹和 ELISA 检测进行了验证。
我们的结果证明，痫愈胶囊通过调节肠道微生物群和血清脂质代谢，尤其是通过调节 AKT1、INS 和 IL-6 的表达水平来调节神经炎症和甘油磷脂代谢，从而对癫痫发挥良好作用。此外，针对神经炎症途径和调节甘油磷脂代谢可能是一种有前景的癫痫治疗策略。
