Epileptic seizures are characterized by synchronized discharges of neurons, leading to the activation of inflammatory responses that in turn contributes to seizure progression. Berberine (BBR), a bioactive constituent extracted from berberis, has been known to relieve seizures in rodent models. In this study, we synthesized two derivatives of berberine (BBR-D1 and BBR-D2) to compare their seizure reducing effect with BBR in pentylenetetrazole (PTZ)-induced seizures in zebrafish. We found a structure-activity relationship between hydrophilic/hydrophobic composition of the derivatives and their anticonvulsant activity. We also investigated the underlying mechanism related to their anti-inflammatory effect during seizures. BBR and its derivatives increased the seizure onset latency and suppressed the seizure-like behavior after PTZ treatment. Zebrafish larvae pretreated with BBR and its derivatives showed recovery on c-fos expression and neuronal discharges during seizures. The inflammatory responses occurred during the progression of seizures, including the recruitment of macrophages and neutrophils as well as an up-regulation of tumor necrosis factor alpha (TNFα), interleukin 1 beta (il1β), and interleukin 6 (il6). This effect was significantly suppressed by the pretreatment of BBR and its derivatives. Our results suggest that BBR and its derivatives attenuate PTZ-induced seizures and modulate anti-inflammatory effect to potentially protect zebrafish from the occurrence of further seizures. From the tested compounds, BBR-D1 (the hydrophilic berberrubine) showed the strongest seizure reducing effect.

Two derivatives of berberine (BBR-D1 and BBR-D2) were synthesized to compare their seizure reducing effect with BBR in pentylenetetrazole (PTZ)-induced seizures in zebrafish. BBR and its derivatives increased the seizure onset latency and suppressed the seizure-like behavior after PTZ treatment. Zebrafish larvae pretreated with BBR and its derivatives showed recovery on c-fos expression and neuronal discharges during seizures. The inflammatory responses occurred during the progression of seizures, including the recruitment of macrophages and neutrophils as well as an up-regulation of tumor necrosis factor alpha (TNFα), interleukin 1 beta (il1β), and interleukin 6 (il6). This effect was significantly suppressed by the pretreatment of BBR and its derivatives.

中文翻译：

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小ber碱及其衍生物抗炎相关的保护机制，减轻斑马鱼中ent四唑诱导的癫痫发作。

癫痫性癫痫发作的特征在于神经元同步放电，导致炎症反应的激活，继而促进癫痫发作的进展。小ber碱（BBR）是一种从小ber提取的生物活性成分，可减轻啮齿动物模型的癫痫发作。在这项研究中，我们合成了小of碱的两种衍生物（BBR-D1和BBR-D2），以比较它们与戊苯四氮（PTZ）引起的斑马鱼癫痫发作中的减少癫痫发作作用。我们发现了衍生物的亲水/疏水成分与其抗惊厥活性之间的构效关系。我们还研究了与癫痫发作期间抗炎作用相关的潜在机制。BTZ及其衍生物增加了PTZ治疗后癫痫发作的潜伏期并抑制了癫痫样行为。BBR及其衍生物预处理的斑马鱼幼虫在癫痫发作期间显示c-fos表达和神经元放电恢复。炎症反应发生在癫痫发作的过程中，包括巨噬细胞和中性粒细胞的募集以及肿瘤坏死因子α（TNFα），白介素1 beta（il1β）和白介素6（il6）的上调。BBR及其衍生物的预处理显着抑制了该作用。我们的研究结果表明，BBR及其衍生物可减轻PTZ诱导的癫痫发作并调节抗炎作用，从而有可能保护斑马鱼免于进一步发作。从测试的化合物中，BBR-D1（亲水性小ber红素）显示出最强的癫痫发作减轻作用。炎症反应发生在癫痫发作的过程中，包括巨噬细胞和中性粒细胞的募集以及肿瘤坏死因子α（TNFα），白介素1 beta（il1β）和白介素6（il6）的上调。BBR及其衍生物的预处理显着抑制了该作用。我们的研究结果表明，BBR及其衍生物可减轻PTZ诱导的癫痫发作并调节抗炎作用，从而有可能保护斑马鱼免于进一步发作。从测试的化合物中，BBR-D1（亲水性小rub红素）显示出最强的减少癫痫发作的作用。炎症反应发生在癫痫发作的过程中，包括巨噬细胞和中性粒细胞的募集以及肿瘤坏死因子α（TNFα），白介素1 beta（il1β）和白介素6（il6）的上调。BBR及其衍生物的预处理显着抑制了该作用。我们的研究结果表明，BBR及其衍生物可减轻PTZ诱导的癫痫发作并调节抗炎作用，从而有可能保护斑马鱼免于进一步发作。从测试的化合物中，BBR-D1（亲水性小rub红素）显示出最强的癫痫发作减轻作用。BBR及其衍生物的预处理显着抑制了该作用。我们的研究结果表明，BBR及其衍生物可减轻PTZ诱导的癫痫发作并调节抗炎作用，从而有可能保护斑马鱼免于进一步发作。从测试的化合物中，BBR-D1（亲水性小rub红素）显示出最强的癫痫发作减轻作用。BBR及其衍生物的预处理显着抑制了该作用。我们的研究结果表明，BBR及其衍生物可减轻PTZ诱导的癫痫发作并调节抗炎作用，从而有可能保护斑马鱼免于进一步发作。从测试的化合物中，BBR-D1（亲水性小rub红素）显示出最强的减少癫痫发作的作用。

合成了两种小ber碱衍生物（BBR-D1和BBR-D2），以比较它们与戊二烯四唑（PTZ）引起的斑马鱼癫痫发作中的减少癫痫发作作用。BTZ及其衍生物增加了PTZ治疗后癫痫发作的潜伏期并抑制了癫痫样行为。BBR及其衍生物预处理的斑马鱼幼虫在癫痫发作期间显示c-fos表达和神经元放电恢复。炎症反应发生在癫痫发作的过程中，包括巨噬细胞和中性粒细胞的募集以及肿瘤坏死因子α（TNFα），白介素1 beta（il1β）和白介素6（il6）的上调。BBR及其衍生物的预处理显着抑制了该作用。