Department of Pharmacology, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu, Tamil Nadu, 603 203, India.
Sci Rep. 2024 Aug 30;14(1):20207. doi: 10.1038/s41598-024-70933-2.
Migraine is a debilitating neurological disorder impacting millions worldwide. Calcitonin Gene-Related Peptide (CGRP) has emerged as a key player in migraine pathophysiology, leading to the development of targeted therapies. This study reviews novel CGRP-targeted treatments, including monoclonal antibodies small molecule inhibitors/nutraceuticals and introduces Asarinin as a potential modulator of the pathway. Asarinin, a natural compound found in various plants, is examined for its pharmacological potential in migraine management. Pharmacokinetic assessments, toxicological modelling, molecular property analysis, and network pharmacology were conducted. Molecular docking and dynamics studies with CGRP reveal potential interactions, providing a foundation for understanding Asarinin's therapeutic effects. Asarinin's favourable pharmacokinetics, safety profile, and bioactivity, supporting its candidacy as a therapeutic agent. In-depth molecular docking studies with the CGRP receptor (PDB: 6ZHO) demonstrate strong binding affinity (- 10.3kcal/mol), while molecular dynamics simulations unveil the dynamic behavior of the Asarinin-CGRP complex, (- 10.53 kcal/mol) for Atogepant-CGRP complex. Network analysis highlights key proteins in migraine pathology, indicating Asarinin's potential efficacy. The groundwork for future investigations, suggests Asarinin as a promising candidate for migraine management by targeting OPRM1 pathway. The integration of diverse assessments provides a comprehensive understanding of Asarinin's potential and paves the way for further preclinical and clinical research.
偏头痛是一种全球性的致残性神经疾病，影响着数百万人。降钙素基因相关肽（CGRP）已成为偏头痛病理生理学中的关键因素，导致靶向治疗的发展。本研究综述了新型 CGRP 靶向治疗方法，包括单克隆抗体、小分子抑制剂/营养保健品，并介绍了细辛脂素作为该途径的潜在调节剂。细辛脂素是一种存在于多种植物中的天然化合物，研究了其在偏头痛管理中的药理潜力。进行了药代动力学评估、毒理学建模、分子特性分析和网络药理学研究。用 CGRP 进行分子对接和动力学研究揭示了潜在的相互作用，为理解细辛脂素的治疗效果提供了基础。细辛脂素具有良好的药代动力学、安全性和生物活性，支持其作为治疗剂的候选资格。与 CGRP 受体（PDB：6ZHO）的深入分子对接研究表明其具有很强的结合亲和力（-10.3kcal/mol），而分子动力学模拟揭示了细辛脂素-CGRP 复合物的动态行为，其与阿托替坦-CGRP 复合物的结合亲和力为-10.53 kcal/mol。网络分析突出了偏头痛发病机制中的关键蛋白，表明细辛脂素具有潜在的疗效。为未来的研究奠定了基础，表明细辛脂素通过靶向 OPRM1 途径成为治疗偏头痛的有希望的候选药物。多种评估的综合提供了对细辛脂素潜力的全面理解，并为进一步的临床前和临床研究铺平了道路。
