Eudesma-4(15), 7-dien-1-β-ol, A promising natural drug candidate for Alzheimer's disease targeting the NMDA pathway: GC-MS identification, molecular docking, pharmacokinetic and molecular dynamic analysis

IF 6.3 2区医学 Q1 BIOLOGY

Computers in biology and medicine Pub Date : 2025-09-27 DOI:10.1016/j.compbiomed.2025.111151

Hanane Ferrassi , Abderrahim Ait Ouchaoui , Mohammed Hakmi , Hamza Ghammaz , Salah Eddine EL Hadad , Youssra EL-Ghandouri , Souad Kartti , Elmostafa El Fahime , Ilhame Bourais , Youssef Elouafy

{"title":"Eudesma-4(15), 7-dien-1-β-ol, A promising natural drug candidate for Alzheimer's disease targeting the NMDA pathway: GC-MS identification, molecular docking, pharmacokinetic and molecular dynamic analysis","authors":"Hanane Ferrassi , Abderrahim Ait Ouchaoui , Mohammed Hakmi , Hamza Ghammaz , Salah Eddine EL Hadad , Youssra EL-Ghandouri , Souad Kartti , Elmostafa El Fahime , Ilhame Bourais , Youssef Elouafy","doi":"10.1016/j.compbiomed.2025.111151","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer's disease (AD) remains a significant global health challenge, with no definitive cure available.</div></div><div><h3>Purpose</h3><div>This study investigates Juglans regia essential oil as a source of therapeutic molecules for AD, targeting the NMDA receptor pathway.</div></div><div><h3>Study design</h3><div><em>& Methods</em>: The essential oil was extracted by hydrodistillation, and the GC-MS analyzed the chemical composition. Antioxidant activity was evaluated using DPPH assay. Molecular docking compared compound affinities to the NMDA receptor against Memantine, with pharmacokinetic analysis evaluating drug-likeness. Interaction and molecular dynamic analysis were also performed.</div></div><div><h3>Results</h3><div>GC-MS identified 34 compounds, predominantly caryophyllene oxide (20.6 %) and β-Eudesmol (10.7 %). The DPPH assay resulted in an IC<sub>50</sub> value of 855.34 μg/mL. Eleven compounds showed superior/equivalent affinities (−7.4 kcal/mol) to Memantine. Eudesma-4(15),7-dien-1-β-ol demonstrated exceptional NMDA receptor interaction, outperforming Memantine in binding affinity, interaction quality, and stability in molecular dynamics while meeting drug-likeness criteria.</div></div><div><h3>Conclusion</h3><div>These findings suggest that Eudesma-4(15),7-dien-1-β-ol from <em>J. regia</em> shows promise as an AD therapeutic candidate via NMDA receptor modulation, warranting clinical investigation to assess its therapeutic efficacy and safety.</div></div>","PeriodicalId":10578,"journal":{"name":"Computers in biology and medicine","volume":"198 ","pages":"Article 111151"},"PeriodicalIF":6.3000,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Computers in biology and medicine","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0010482525015045","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Alzheimer's disease (AD) remains a significant global health challenge, with no definitive cure available.

Purpose

This study investigates Juglans regia essential oil as a source of therapeutic molecules for AD, targeting the NMDA receptor pathway.

Study design

& Methods: The essential oil was extracted by hydrodistillation, and the GC-MS analyzed the chemical composition. Antioxidant activity was evaluated using DPPH assay. Molecular docking compared compound affinities to the NMDA receptor against Memantine, with pharmacokinetic analysis evaluating drug-likeness. Interaction and molecular dynamic analysis were also performed.

Results

GC-MS identified 34 compounds, predominantly caryophyllene oxide (20.6 %) and β-Eudesmol (10.7 %). The DPPH assay resulted in an IC₅₀ value of 855.34 μg/mL. Eleven compounds showed superior/equivalent affinities (−7.4 kcal/mol) to Memantine. Eudesma-4(15),7-dien-1-β-ol demonstrated exceptional NMDA receptor interaction, outperforming Memantine in binding affinity, interaction quality, and stability in molecular dynamics while meeting drug-likeness criteria.

Conclusion

These findings suggest that Eudesma-4(15),7-dien-1-β-ol from J. regia shows promise as an AD therapeutic candidate via NMDA receptor modulation, warranting clinical investigation to assess its therapeutic efficacy and safety.

Abstract Image

查看原文本刊更多论文

Eudesma-4(15), 7-dien-1-β-ol，一种靶向NMDA通路的阿尔茨海默病天然候选药物：GC-MS鉴定、分子对接、药代动力学和分子动力学分析

阿尔茨海默病（AD）仍然是一个重大的全球健康挑战，没有明确的治疗方法。目的研究核桃精油作为一种靶向NMDA受体通路的AD治疗分子的来源。研究设计方法：采用水蒸气蒸馏法提取挥发油，GC-MS分析挥发油化学成分。采用DPPH法测定其抗氧化活性。分子对接比较了化合物与NMDA受体对美金刚的亲和力，并通过药代动力学分析评估药物相似性。并进行了相互作用和分子动力学分析。结果gc - ms共鉴定出34个化合物，主要为石竹烯氧化物（20.6%）和β-丁香酚（10.7%）。DPPH测定的IC50值为855.34 μg/mL。11个化合物对美金刚胺具有优异或相当的亲和力（−7.4 kcal/mol）。Eudesma-4(15)，7-dien-1-β-ol表现出特殊的NMDA受体相互作用，在结合亲和力、相互作用质量和分子动力学稳定性方面优于美金刚，同时满足药物相似标准。结论王参Eudesma-4(15)，7-二烯-1-β-醇通过NMDA受体调节，有望成为阿尔兹海默病的治疗候选药物，值得临床研究以评估其治疗效果和安全性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Computers in biology and medicine 工程技术-工程：生物医学

CiteScore

11.70

自引率

10.40%

发文量

1086

审稿时长

74 days

期刊介绍： Computers in Biology and Medicine is an international forum for sharing groundbreaking advancements in the use of computers in bioscience and medicine. This journal serves as a medium for communicating essential research, instruction, ideas, and information regarding the rapidly evolving field of computer applications in these domains. By encouraging the exchange of knowledge, we aim to facilitate progress and innovation in the utilization of computers in biology and medicine.