Medicinal plants of the genus Aconitum are one of the most commonly used herbs in traditional medicine in East Asia to treat conditions related to the heart, pain, or inflammation. However, these herbs are also dangerous as accidental poisoning due to misuse is a recurring issue. These plants contain a number of diester‐diterpenoid alkaloid compounds and aconitine is the most abundant and active one. This study investigated neurotoxicity of aconitine to zebrafish embryos in early development in relation to serotonin regulation. Experimental results showed that aconitine exposure (1, 10, and 100 μM) increased frequency of coiling behavior in zebrafish embryos in a dose‐dependent manner and this effect can be triggered by either exposure to 5‐hydroxytryptamine 1A (5‐HT1A) receptor agonist (±)‐8‐hydroxy‐2‐(dipropylamino)tetralin (8‐OH‐DPAT) or overexpression of serotonin receptor 5‐htr1ab. At the same time, coiling behavior caused by aconitine exposure could be rescued by co‐exposure to 5‐HT1A receptor antagonist WAY‐100635 Maleate (WAY100635) and knockdown of 5‐htr1ab using morpholino. Exposure to aconitine also significantly increased serotonin receptor 5‐htr1ab and 5‐htr1bd gene expression at 24 h post fertilization (hpf), but decreased their expression and protein expression of the serotonin receptor at 96 hpf with the high dose. These results suggest that neurotoxicity caused by aconitine is mediated through the 5‐HT receptor.

中文翻译：

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乌头碱通过斑马鱼胚胎中的 5-羟色胺受体破坏血清素神经传递

乌头属药用植物是东亚传统医学中最常用的草药之一，用于治疗与心脏、疼痛或炎症相关的疾病。然而，这些草药也很危险，因为误用导致的意外中毒是一个反复出现的问题。这些植物含有许多二酯-二萜类生物碱化合物，乌头碱是最丰富和最活跃的一种。本研究调查了乌头碱对早期发育中与血清素调节相关的斑马鱼胚胎的神经毒性。实验结果表明，乌头碱暴露（1、10 和 100 μM）以剂量依赖性方式增加了斑马鱼胚胎卷曲行为的频率，这种效应可以通过暴露于 5-羟色胺 1A (5-HT1A) 受体激动剂来触发(±)-8-羟基-2-(二丙基氨基)萘满 (8-OH-DPAT) 或血清素受体的过度表达5-htr1ab。同时，通过与 5-HT1A 受体拮抗剂 WAY-100635 马来酸盐 (WAY100635) 共同暴露和使用吗啉敲除5-htr1ab可以挽救由乌头碱暴露引起的卷曲行为。暴露于乌头碱还显着增加了受精后 24 小时 (hpf) 的血清素受体5-htr1ab和5-htr1bd基因表达，但在 96 hpf 高剂量时降低了它们的表达和血清素受体的蛋白质表达。这些结果表明乌头碱引起的神经毒性是通过 5-HT 受体介导的。