Wimbarti Supra, Tallei Trina Ekawati, Kairupan Bernabas Harold Ralph, Kapantow Nova Hellen, Ekatanti Dewi, Fatriani Rizka, Kusuma Wisnu Ananta, - Fatimawali, Celik Ismail
Faculty of Psychology, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia.
Department of Biology, Faculty of Mathematics and Natural Sciences, Sam Ratulangi University, Manado 95115, North Sulawesi, Indonesia.
Curr Pharm Des. 2025;31(17):1370-1387. doi: 10.2174/0113816128335217241031033104.
Psychosis, marked by detachment from reality, includes symptoms like hallucinations and delusions. Traditional herbal remedies like kratom are gaining attention for psychiatric conditions. This was aimed at comprehending the molecular mechanisms of Kratom's antipsychotic effects utilizing a multi-modal computational approach.
This study employed network pharmacology followed by molecular docking and molecular dynamics simulation study to investigate the potential antipsychotic properties of kratom compounds by identifying their key molecular targets and interactions.
Compounds present in kratom interact with a variety of receptors and proteins that play a pivotal role in neurotransmission, neurodevelopment, and cellular signaling. These interactions, particularly with dopamine and serotonin receptors, various proteins, and pathways, suggest a complex influence on psychiatric conditions. Both mitragynine and zotepine (an atypical antipsychotic drug) display significant binding affinities for 5HTR2A receptors, suggesting their potential for modulating related physiological pathways. Mitragynine displayed higher flexibility in binding compared to zotepine, which showed a more stable interaction. Hydrogen bond analysis revealed a more variable interaction profile for mitragynine than zotepine.
The research findings suggest that the interaction between kratom compounds and essential brain receptors could influence psychiatric conditions. Notably, both mitragynine (a key kratom component) and zotepine (an antipsychotic) bind to the 5HTR2A receptor, suggesting the potential for kratom to modulate similar pathways. Interestingly, mitragynine's flexible binding mode compared to zotepine might indicate a more diverse range of effects. Overall, the findings suggest complex interactions between kratom and the brain's signaling system, warranting further investigation into its potential therapeutic effects.
以与现实脱节为特征的精神病包括幻觉和妄想等症状。传统草药如 kratom 在精神疾病方面正受到关注。本研究旨在利用多模态计算方法理解 kratom 抗精神病作用的分子机制。
本研究采用网络药理学，随后进行分子对接和分子动力学模拟研究，通过识别其关键分子靶点和相互作用来研究 kratom 化合物的潜在抗精神病特性。
kratom 中存在的化合物与多种在神经传递、神经发育和细胞信号传导中起关键作用的受体和蛋白质相互作用。这些相互作用，特别是与多巴胺和 5-羟色胺受体、各种蛋白质及信号通路的相互作用，表明其对精神疾病有复杂影响。吗啡碱和氯氮平（一种非典型抗精神病药物）对 5HTR2A 受体均显示出显著的结合亲和力，表明它们具有调节相关生理途径的潜力。与氯氮平相比，吗啡碱在结合时表现出更高的灵活性，而氯氮平显示出更稳定的相互作用。氢键分析显示，吗啡碱的相互作用模式比氯氮平更具变异性。
研究结果表明，kratom 化合物与大脑重要受体之间的相互作用可能影响精神疾病。值得注意的是，吗啡碱（kratom 的一种关键成分）和氯氮平（一种抗精神病药物）均与 5HTR2A 受体结合，表明 kratom 具有调节类似途径的潜力。有趣的是，与氯氮平相比，吗啡碱灵活的结合模式可能表明其具有更广泛的作用范围。总体而言，研究结果表明 kratom 与大脑信号系统之间存在复杂的相互作用，有必要进一步研究其潜在的治疗效果。
