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首页> 外文期刊>Frontiers in Neuropharmacology >Hesperidin Interacts With CREB-BDNF Signaling Pathway to Suppress Pentylenetetrazole-Induced Convulsions in Zebrafish
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Hesperidin Interacts With CREB-BDNF Signaling Pathway to Suppress Pentylenetetrazole-Induced Convulsions in Zebrafish

机译：Hesperidin与CREB-BDNF信号传导途径相互作用，以抑制斑马鱼中的五苯甲唑诱导的痉挛

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摘要

Hesperidin (3,5,7-trihydroxyflavanone 7-rhamnoglucoside) is a β-7-rutinoside of hesperetin (4′-methoxy-3′,5,7-trihydroxyflavanone), abundantly found in citrus fruits and known to interact with various cellular pathways to show a variety of pharmacological effects. The present study was envisaged to understand the anticonvulsant effect of hesperidin in a zebrafish model of pentylenetetrazole (PTZ)-induced convulsions, with the support of in silico docking. Healthy zebrafish larvae were preincubated with hesperidin (1, 5, and 10 μM) for 1 h, before PTZ exposure. Hesperidin treatment significantly increased the seizure latency and minimized PTZ-induced hyperactive responses. A significant reduction in c-fos expression further supported the suppression of neuronal excitation following hesperidin incubation in the larvae exposed to PTZ. The treatment also modulated larval bdnf expression and reduced the expression of il-10. The results of in vivo studies were further supported by in silico docking analysis, which showed the affinity of hesperidin for the N-methyl-D-aspartate receptor, the gamma-aminobutyric acid receptor, Interleukin 10 and the TrkB receptor of brain-derived neurotrophic factor. The results concluded that hesperidin suppresses PTZ-mediated seizure in zebrafish larvae through interaction with the central CREB–BDNF pathway.
机译：Hesperidin（3,5,7-三羟基吡啶酮7- rhamnogoside）是伊伯特蛋白（4'-甲氧基-3'，5,7-三羟基氟苯酮）的β-7- rutinoside，大量发现在柑橘类水果中并已知与各种细胞相互作用途径显示各种药理作用。本研究设想了解橙皮蛋白在斑马丁唑（PTZ） - 诱导的抽搐的斑马鱼模型中的抗惊厥作用，硅基对接的支持。在PTZ暴露之前，用橙皮蛋白（1,5和10μm）预先孵育健康的斑马鱼幼虫。 Hesperidin治疗显着提高了癫痫发作潜伏期，最小化了PTZ诱导的过度响应。 C-FOS表达的显着降低进一步支持在暴露于PTZ的幼虫中的橙皮蛋白孵育后抑制神经元激发。该治疗还调用幼虫BDNF表达并降低IL-10的表达。在硅基对接分析中进一步支持体内研究的结果，该分析表明了橙皮素对N-甲基-D-天冬氨酸受体，γ-氨基丁酸受体，白细胞介素10和脑衍生的神经营养的TRKB受体的亲和力因素。结果得出结论认为，哈菲蛋白通过与中央Creb-BDNF途径的相互作用抑制斑马鱼幼虫的PTZ介导的癫痫发作。

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