通过网络药理学、分子对接和高脂饮食诱导仓鼠动脉粥样硬化的体内药效研究,探索 1,8-ineole 的抗动脉粥样硬化活性。

IF 3.9 2区 化学 Q2 CHEMISTRY, APPLIED Molecular Diversity Pub Date : 2024-10-27 DOI:10.1007/s11030-024-11015-3
Shreya R Savla, Lokesh Kumar Bhatt
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引用次数: 0

摘要

肝脏 X 受体(LXRs)的抗动脉粥样硬化潜力归因于其在巨噬细胞介导的炎症和促进胆固醇逆向转运中的抑制作用。本研究旨在通过网络药理学、分子对接和高脂饮食诱导的仓鼠动脉粥样硬化的体内疗效研究,评估肝X受体激动剂1,8-蒎烯(桉叶油醇)对动脉粥样硬化的疗效。通过识别 1,8-松油醇和动脉粥样硬化的潜在靶点,进行了网络药理学分析,随后构建了成分-靶点-疾病和蛋白质-蛋白质相互作用网络。对靶点进行了基因本体和 KEGG 通路富集分析。选出前 5 个靶点进行分子对接研究。用雄性金色叙利亚仓鼠诱导动脉粥样硬化,并验证了网络药理学的结果。结果发现,1,8-蒎烯与动脉粥样硬化有 51 个重叠靶点。在蛋白质相互作用研究中,排名前五位的蛋白质分别是 PPARG、FXR、ABCA-1、ABCG1 和 LXRΑ。KEGG 通路分析和分子对接显示,ABCA-1 和 LXRΑ 在动脉粥样硬化中具有相关性。动物实验表明,与疾病对照组的主动脉相比,使用 1,8-松油治疗的动物主动脉动脉粥样硬化病变有所改善。在接受 1,8-ineole 治疗的动物体内,ABCA-1 水平和炎症标志物呈剂量依赖性下降,与正常动物体内的水平相当。总之,1,8-松油通过LXRΑ诱导的ABCA-1过表达对金色叙利亚仓鼠具有抗动脉粥样硬化的作用。
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Exploration of anti-atherosclerotic activity of 1,8-cineole through network pharmacology, molecular docking, and in vivo efficacy studies in high-fat-diet-induced atherosclerosis in hamsters.

The anti-atherogenic potential of liver X receptors (LXRs) has been attributed to their inhibitory role in macrophage-mediated inflammation and promotion of reverse cholesterol transport. This study aimed to evaluate the efficacy of an LXR agonist, 1,8-cineole (Eucalyptol), in atherosclerosis through network pharmacology, molecular docking, and in vivo efficacy studies in high-fat-diet-induced atherosclerosis in hamsters. Network pharmacology analysis was performed by identifying potential targets of 1,8-Cineole and atherosclerosis, followed by the construction of component-target-disease and protein-protein interaction networks. Gene Ontology and KEGG pathway enrichment analysis of targets were performed. The top 5 targets were selected for molecular docking studies. Atherosclerosis was induced in male Golden Syrian hamsters, and the results of network pharmacology were verified. Fifty-one overlapped targets were identified for 1,8-cineole and atherosclerosis. In the protein-protein interaction studies, the top 5 ranked proteins were PPARG, FXR, ABCA-1, ABCG1, and LXRΑ. KEGG pathway analysis and molecular docking showed that ABCA-1 and LXRΑ were correlated in atherosclerosis. Animal studies showed amelioration of atherosclerotic lesions in the aorta of animals treated with 1,8-cineole compared to disease control aortas. A dose-dependent attenuation in ABCA-1 levels and inflammatory markers was observed in animals treated with 1,8-cineole, comparable to its levels in normal animals. In conclusion, 1,8-cineole showed anti-atherosclerotic effects in Golden Syrian hamsters via LXRΑ-induced ABCA-1 overexpression.

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来源期刊
Molecular Diversity
Molecular Diversity 化学-化学综合
CiteScore
7.30
自引率
7.90%
发文量
219
审稿时长
2.7 months
期刊介绍: Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including: combinatorial chemistry and parallel synthesis; small molecule libraries; microwave synthesis; flow synthesis; fluorous synthesis; diversity oriented synthesis (DOS); nanoreactors; click chemistry; multiplex technologies; fragment- and ligand-based design; structure/function/SAR; computational chemistry and molecular design; chemoinformatics; screening techniques and screening interfaces; analytical and purification methods; robotics, automation and miniaturization; targeted libraries; display libraries; peptides and peptoids; proteins; oligonucleotides; carbohydrates; natural diversity; new methods of library formulation and deconvolution; directed evolution, origin of life and recombination; search techniques, landscapes, random chemistry and more;
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