中药治疗癫痫的前沿进展：聚焦神经炎症、胶质细胞重塑与肠脑轴

Frontiers in the Use of Traditional Chinese Medicine for Epilepsy Treatment: Focusing on Neuroinflammation, Glial Cell Remodeling and the Gut-Brain Axis

摘要: 癫痫是全球最常见的慢性神经系统疾病之一，其核心病理并非单纯的神经元异常放电，而是由兴奋/抑制失衡、神经炎症、胶质细胞反应、血脑屏障破坏、氧化应激、细胞死亡、肠脑轴紊乱与脑网络重构共同驱动的动态过程。尽管现代抗癫痫发作药物可有效控制部分患者发作，仍约三分之一患者发展为药物难治性癫痫，且认知障碍、焦虑抑郁、海马神经元损伤和生活质量下降等共病问题尚缺乏理想干预策略。中药复方、单味药及其活性成分具有多成分、多靶点、多通路协同调节特征，近年来在癫痫发作控制、抗癫痫发生、海马神经保护、胶质细胞调控和肠脑轴干预等方面显示出新的研究价值。本文以“神经炎症–胶质细胞重塑–肠脑轴”为主线，系统梳理2022~2025年中药治疗癫痫的前沿进展，重点总结天麻、钩藤、石菖蒲、黄芩、黄连、丹参、枸杞等相关复方及天麻素、钩藤碱、α-细辛醚、黄芩苷/黄芩素、小檗碱、槲皮素、等活性成分的药理机制。现有证据提示，中药干预可能通过恢复GABA/谷氨酸稳态、抑制IL-1β/HMGB1/TLR4/NF-κB和NLRP3炎症小体、调控星形胶质细胞A1-like/A2-like功能状态、降低铁死亡和焦亡、改善菌群–脂质代谢轴及保护血脑屏障等途径，发挥抗癫痫与神经保护效应。然而，临床证据质量、药材质量控制、复方物质基础、药代动力学、药物相互作用和长期安全性仍是制约转化的关键瓶颈。未来研究应以标准化动物模型、连续脑电监测、多组学整合、单细胞/空间组学、真实世界研究和高质量随机对照试验为核心，推动中药从经验性辅助治疗走向机制明确、证据充分、可转化的癫痫疾病修饰策略。

Abstract: Epilepsy is one of the most common chronic neurological disorders worldwide. Its core pathophysiology is not merely abnormal neuronal firing, but a dynamic process driven by excitation/inhibition imbalance, neuroinflammation, glial responses, blood-brain barrier disruption, oxidative stress, cell death, gut-brain axis dysregulation, and large-scale brain network reconfiguration. Although current antiseizure medications effectively control seizures in a subset of patients, approximately one-third develop drug-resistant epilepsy. Moreover, comorbidities such as cognitive impairment, anxiety, depression, hippocampal neuronal loss, and diminished quality of life remain inadequately addressed by existing therapeutic strategies. Chinese herbal formulas, single herbs, and their bioactive constituents exhibit synergistic regulation with multi-component, multi-target, and multi-pathway features. In recent years, they have shown renewed research value in seizure control, anti-epileptogenesis, hippocampal neuroprotection, glial modulation, and gut-brain axis intervention. This review focuses on the “neuroinflammation, glial remodeling, gut-brain axis” and systematically examines the frontier advances in traditional Chinese medicine for epilepsy from 2022 to 2025. We highlight the pharmacological mechanisms of representative formulas containing Gastrodia elata, Uncaria rhynchophylla, Acorus tatarinowii, Scutellaria baicalensis, Coptis chinensis, Salvia miltiorrhiza, and Lycium barbarum, as well as active ingredients including gastrodin, rhynchophylline, α-asarone, baicalin/baicalein, berberine and quercetin. Available evidence suggests that Chinese herbal interventions may exert antiseizure and neuroprotective effects through restoring GABA/glutamate homeostasis, suppressing IL-1β/HMGB1/TLR4/NF-κB and NLRP3 inflammasome pathways, modulating the A1-like/A2-like functional states of astrocytes, reducing ferroptosis and pyroptosis, improving the microbiota-lipid metabolism axis, and preserving blood-brain barrier integrity. However, key translational bottlenecks remain, including the quality of clinical evidence, quality control of medicinal materials, material basis of formulas, pharmacokinetics, drug-drug interactions, and long-term safety. Future research should prioritize standardized animal models, continuous electroencephalographic monitoring, multi-omics integration, single-cell and spatial omics, real-world studies, and high-quality randomized controlled trials, so as to advance traditional Chinese medicine from empirical adjunctive therapy toward mechanistically defined, evidence-based, and translatable disease-modifying strategies for epilepsy.