背景:Koumine是从秀丽线虫中提取的最丰富的生物碱。.我们课题组的初步研究表明,koumine具有显著的抗焦虑作用,但这需要进一步证实。
目的:研究苦参素对捕食性声音(PS)应激性焦虑模型的抗焦虑作用,并初步探讨其治疗作用靶点和分子机制。
方法:确定了在急性PS应激诱导的焦虑动物模型中,koumine的抗焦虑作用。然后,涉及焦虑症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,已确定。最后,为了阐明koumine对转运蛋白18kDa(TSPO)的影响,通过表面等离子体共振(SPR)技术评估了Koumine与TSPO之间的亲和力。
结果:Koumine治疗减轻了开放场测试和高架迷宫测试中急性PS应激后的焦虑样行为。PS暴露显着降低PFC中的孕酮和别孕烯醇酮水平,臀部,Amy和血浆ACTH和CORT水平升高,和koumine管理显著逆转了这些影响。最后,可靠的SPR结果表明,Koumine与TSPO的KD为155.33±11.0μM,表明koumine是人类TSPO高亲和力配体,其亲和力与典型的TSPO配体相当。
结论:我们的结果表明,在PS诱导的焦虑模型中,koumine具有明显的抗焦虑作用。靶向TSPO-神经类固醇-HPA轴可能是koumine发挥其抗焦虑作用的重要机制。
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.
OBJECTIVE: 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.
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 KD 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.
CONCLUSIONS: 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.