The anxiolytic effect of koumine on a predatory sound stress-induced anxiety model and its associated molecular mechanisms,Phytomedicine

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The anxiolytic effect of koumine on a predatory sound stress-induced anxiety model and its associated molecular mechanisms
Phytomedicine ( IF 6.7 ) Pub Date : 2022-06-03 , DOI: 10.1016/j.phymed.2022.154225
Bojun Xiong ₁ , Zhifeng Zhong ₂ , Chaojie Chen ₃ , Huihui Huang ₄ , Jinxiang Lin ₁ , Ying Xu ₄ , Jian Yang ₄ , Changxi Yu ₄

Affiliation

Background

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.

Study design and methods

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.

Results

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_D 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.

Conclusion

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.

中文翻译：

koumine 对掠食性声音应激诱导的焦虑模型的抗焦虑作用及其相关分子机制

背景

Koumine是从Gelsemium elegans Benth中提取的最丰富的生物碱。我们课题组的初步研究表明，koumine具有显着的抗焦虑作用，但这需要进一步证实。

假设/目的

探讨koumine对掠食性声音（PS）应激诱导的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。

研究设计和方法

测定了 koumine 在急性 PS 应激引起的焦虑动物模型中的抗焦虑作用。然后，确定了与焦虑症有关的主要大脑区域的神经类固醇水平，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 koumine 对转运蛋白 18 kDa (TSPO) 的影响，通过表面等离子共振 (SPR) 技术评估了 koumine 和 TSPO 之间的亲和力。

结果

Koumine 治疗减轻了旷场试验和高架十字迷宫试验中急性 PS 应激后的焦虑样行为。PS 暴露显着降低了 PFC、Hip 和 Amy 中的孕酮和异孕酮水平，并增加了血浆中的 ACTH 和 CORT 水平，而 koumine 给药显着逆转了这些影响。最后，可靠的 SPR 结果表明，koumine 与 TSPO 的 K _D为 155.33 ± 11.0 μM，表明 koumine 是一种人类 TSPO 高亲和力配体，具有与典型 TSPO 配体相当的亲和力。