Breckenridge Audrey, Basnyat Sanskriti, Fitch Eva, Carpenter-Swanson Colleen
Department of Biology, University of Richmond, Richmond, VA, United States.
Front Pharmacol. 2025 Jun 26;16:1628324. doi: 10.3389/fphar.2025.1628324. eCollection 2025.
Current epilepsy treatments often fail to provide sufficient control over seizures, highlighting the need for new therapeutic agents. Vitexin, a flavone with antioxidant, anti-inflammatory, and neuroprotective properties, was previously shown to suppress seizure activity in rodent models. Utilizing zebrafish, this study further evaluates the antiseizure properties of vitexin and for the first time, examines the related flavone glycosides: isovitexin, vitexin 2-O-rhamnoside, vitexin-4-O-glucoside and saponarin. We initially tested the ability of the compounds to reduce behavioral seizures stimulated by the GABA receptor antagonists (pentylenetetrazole: PTZ and picrotoxin: PTX) and spontaneous seizures in a genetic epilepsy model (Dravet syndrome, zebrafish larvae). Seizure behavior was quantified in 5-day old larvae via automated tracking with a DanioVision monitoring chamber linked to EthoVision XT 15 software. Microelectrode array electrophysiology (MEA) was then used to examine the effects on PTZ-induced seizure-like brain activity. While having no effect on basal locomotion, vitexin and isovitexin significantly reduced seizure activity in PTZ-treated zebrafish. None of the flavones exhibited antiseizure effects in the PTX-induced epilepsy model. Additional studies with vitexin demonstrated that though it did not suppress spontaneous seizure behaviors in our genetic model of epilepsy, it did significantly inhibit PTZ-induced electrographic activity. These findings support the continued exploration of the translational potential of the vitexin scaffold. This work advances our search for safer, more effective antiseizure drugs and could pave the way for vitexin-based treatments for epilepsy and related disorders.
目前的癫痫治疗方法往往无法充分控制癫痫发作，这凸显了对新型治疗药物的需求。牡荆素是一种具有抗氧化、抗炎和神经保护特性的黄酮，此前已被证明可在啮齿动物模型中抑制癫痫活动。本研究利用斑马鱼进一步评估了牡荆素的抗癫痫特性，并首次研究了相关的黄酮苷：异牡荆素、牡荆素2-O-鼠李糖苷、牡荆素-4-O-葡萄糖苷和肥皂草苷。我们首先测试了这些化合物减少由GABA受体拮抗剂（戊四氮：PTZ和印防己毒素：PTX）刺激的行为性癫痫发作以及在遗传性癫痫模型（Dravet综合征，斑马鱼幼虫）中减少自发性癫痫发作的能力。通过与EthoVision XT 15软件相连的DanioVision监测室对5日龄幼虫的癫痫行为进行自动跟踪定量。然后使用微电极阵列电生理学（MEA）来检查对PTZ诱导的癫痫样脑活动的影响。虽然对基础运动没有影响，但牡荆素和异牡荆素显著降低了PTZ处理的斑马鱼的癫痫活动。在PTX诱导的癫痫模型中，这些黄酮均未表现出抗癫痫作用。对牡荆素的进一步研究表明，尽管它在我们的遗传性癫痫模型中没有抑制自发性癫痫行为，但它确实显著抑制了PTZ诱导的电图活动。这些发现支持继续探索牡荆素支架的转化潜力。这项工作推动了我们对更安全、更有效的抗癫痫药物的探索，并可能为基于牡荆素的癫痫及相关疾病治疗铺平道路。
