Department of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China.
Department of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China; Department of High Altitude Operational Medicine, College of High Altitude Military Medicine, Army Medical University (Third Military Medical University), Chongqing 400038, China.
Phytomedicine. 2022 Aug;103:154225. doi: 10.1016/j.phymed.2022.154225. Epub 2022 Jun 3.
Koumine is the most abundant alkaloid extracted from Gelsemium elegans Benth.. Preliminary studies by our research group have shown that koumine has significant anxiolytic effect, but this needs to be further confirmed.
HYPOTHESIS/PURPOSE: To investigate the potential anxiolytic effect of koumine on predatory sound (PS) stress-induced anxiety models and preliminarily explore its therapeutic targets and molecular mechanisms.
The anxiolytic effect of koumine in an animal model of acute PS stress-induced anxiety were determined. Then, neurosteroids levels in the main brain regions involved in anxiety disorders, as well as plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels, were determinated. Finally, to clarify the effect of koumine on translocator protein 18 kDa (TSPO), the affinity between koumine and TSPO was evaluated by surface plasmon resonance (SPR) technology.
Koumine treatment mitigated anxiety-like behavior following acute PS stress in the open field test and elevated plus maze test. PS exposure significantly decreased progesterone and allopregnanolone levels in the PFC, Hip, and Amy and increased ACTH and CORT levels in plasma, and koumine administration significantly reversed these effects. Finally, the reliable SPR results showed that the K of koumine with TSPO was 155.33 ± 11.0 μM, indicating that koumine is a human TSPO high-affinity ligand that has an affinity comparable to typical TSPO ligands.
Our results show that koumine has obvious anxiolytic effect in the PS-induced anxiety model. Targeting TSPO-neurosteroids-HPA axis may be an important mechanism by which koumine exerts its anxiolytic effect.
钩吻素甲是从钩吻中提取的最丰富的生物碱。本课题组的初步研究表明，钩吻素甲具有显著的抗焦虑作用，但这需要进一步证实。
假设/目的：研究钩吻素甲对捕食性声音（PS）应激诱导焦虑模型的潜在抗焦虑作用，并初步探讨其治疗靶点和分子机制。
在急性 PS 应激诱导焦虑动物模型中确定钩吻素甲的抗焦虑作用。然后，测定参与焦虑障碍的主要脑区的神经甾体水平以及血浆促肾上腺皮质激素（ACTH）和皮质酮（CORT）水平。最后，为了阐明钩吻素甲对 18kDa 转位蛋白（TSPO）的影响，通过表面等离子体共振（SPR）技术评估钩吻素甲与 TSPO 的亲和力。
钩吻素甲治疗减轻了急性 PS 应激后旷场试验和高架十字迷宫试验中的焦虑样行为。PS 暴露显著降低了 PFC、Hip 和 Amy 中的孕酮和别孕烯醇酮水平，并增加了血浆中的 ACTH 和 CORT 水平，而钩吻素甲给药显著逆转了这些效应。最后，可靠的 SPR 结果表明，钩吻素甲与 TSPO 的 Kd 值为 155.33±11.0 μM，表明钩吻素甲是一种人 TSPO 高亲和力配体，与典型的 TSPO 配体具有相当的亲和力。
我们的结果表明，钩吻素甲在 PS 诱导的焦虑模型中具有明显的抗焦虑作用。靶向 TSPO-神经甾体-HPA 轴可能是钩吻素甲发挥抗焦虑作用的重要机制。
