| Abstrak/Abstract |
Introduction: Estrogen deficiency during menopause is associated with pathological menopausal syndromes and metabolic disorders, including dysregulated lipid metabolism (dyslipidemia). Mahogany is a promising material for use in an alternative treatment for preventing dyslipidemia during menopause. This study investigated the potency of mahogany compounds and their molecular mechanism as an alternative treatment for preventing dyslipidemia during menopause.
Method and materials: The determination of the potential of the compounds of interest was performed by machine learning using KNIME software to identify the potential compounds for HMG-CoA Reductase (HMGCR) inhibitor. Target genes for a potential mahogany compound were obtained from Swiss Target Prediction. Analysis of the KEGG-Pathways, Gene Ontology profiling, and protein-protein interaction networks of the target gene were analyzed.
Results: We identified five compounds: β-sitosterol, swietemacrophyllanin, 7-hydroxy-2-(4-hydroxy-3- methoxyphenyl)-chroman-4-on (7-HMC), scopoletin, and stigmasterol as candidates for HMGCR inhibitors. The target prediction results mined 294 genes. The top 20 hub genes with the highest degree included MAPK1/3, PI3K/AKT, ER1, and mTOR, which played a role in lipid metabolism.
Conclusion: The possible molecular mechanisms mainly involved direct inhibitory pathway of HMGCR and an indirect inhibitory pathway of HMGCR. The tidal inhibitory pathway was Indirectly mediated via the PI3K/AKT, MAPK1/3, MTOR, ER1, and SREBP1/2 signaling pathways. Further investigation is warranted to validate the results of the present study. |
