Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Switzerland; School of Pharmaceutical Sciences, University of Geneva, Switzerland.
Department of Natural Product Chemistry, Medical University of Lublin, Poland.
J Ethnopharmacol. 2023 Dec 5;317:116740. doi: 10.1016/j.jep.2023.116740. Epub 2023 Jun 12.
Epilepsy is one of the most prevalent neurological human diseases, affecting 1% of the population in all age groups. Despite the availability of over 25 anti-seizure medications (ASMs), which are approved in most industrialized countries, approximately 30% of epilepsy patients still experience seizures that are resistant to these drugs. Since ASMs target only limited number of neurochemical mechanisms, drug-resistant epilepsy (DRE) is not only an unmet medical need, but also a formidable challenge in drug discovery.
In this review, we examine recently approved epilepsy drugs based on natural product (NP) such as cannabidiol (CBD) and rapamycin, as well as NP-based epilepsy drug candidates still in clinical development, such as huperzine A. We also critically evaluate the therapeutic potential of botanical drugs as polytherapy or adjunct therapy specifically for DRE.
Articles related to ethnopharmacological anti-epileptic medicines and NPs in treating all forms of epilepsy were collected from PubMed and Scopus using keywords related to epilepsy, DRE, herbal medicines, and NPs. The database clinicaltrials.gov was used to find ongoing, terminated and planned clinical trials using herbal medicines or NPs in epilepsy treatment.
A comprehensive review on anti-epileptic herbal drugs and natural products from the ethnomedical literature is provided. We discuss the ethnomedical context of recently approved drugs and drug candidates derived from NPs, including CBD, rapamycin, and huperzine A. Recently published studies on natural products with preclinical efficacy in animal models of DRE are summarized. Moreover, we highlight that natural products capable of pharmacologically activating the vagus nerve (VN), such as CBD, may be therapeutically useful to treat DRE.
The review highlights that herbal drugs utilized in traditional medicine offer a valuable source of potential anti-epileptic drug candidates with novel mechanisms of action, and with clinical promise for the treatment of drug-resistant epilepsy (DRE). Moreover, recently developed NP-based anti-seizure medications (ASMs) indicate the translational potential of metabolites of plant, microbial, fungal and animal origin.
癫痫是最常见的神经科人类疾病之一，影响所有年龄段人群的 1%。尽管在大多数工业化国家都有 25 种以上的抗癫痫药物（ASM）可用，这些药物已被批准使用，但仍有约 30%的癫痫患者的癫痫发作对这些药物有抗药性。由于 ASM 仅针对有限数量的神经化学机制，因此耐药性癫痫（DRE）不仅是一个未满足的医疗需求，也是药物发现中的一个巨大挑战。
在本综述中，我们检查了最近基于天然产物（NP）批准的癫痫药物，如大麻二酚（CBD）和雷帕霉素，以及仍处于临床开发阶段的基于 NP 的癫痫候选药物，如石杉碱甲。我们还批判性地评估了植物药物作为多疗法或辅助疗法治疗 DRE 的治疗潜力。
从 PubMed 和 Scopus 中使用与癫痫、DRE、草药和 NP 相关的关键词，收集与民族药理学抗癫痫药物和治疗所有形式癫痫的 NP 相关的文章。使用临床试验数据库 clinicaltrials.gov 查找正在进行、已终止和计划使用草药或 NP 治疗癫痫的临床试验。
提供了对民族医学文献中抗癫痫草药和天然产物的全面综述。我们讨论了最近从 NP 中批准的药物和候选药物的民族医学背景，包括 CBD、雷帕霉素和石杉碱甲。总结了最近关于具有 DRE 动物模型中临床前疗效的天然产物的研究。此外，我们强调 CBD 等能够在药理学上激活迷走神经（VN）的天然产物可能对治疗 DRE 具有治疗作用。
该综述强调了传统医学中使用的草药为具有新作用机制的潜在抗癫痫候选药物提供了宝贵的来源，并且具有治疗耐药性癫痫（DRE）的临床潜力。此外，最近开发的基于 NP 的抗癫痫药物（ASM）表明了植物、微生物、真菌和动物来源的代谢物的转化潜力。
