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.
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Abstract
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.
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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