The protective effects of curcumin on metabolic syndrome and its components: In-silico analysis for genes, transcription factors, and microRNAs involved

Abstract

Background: We aimed to identify the molecular mechanisms behind curcumin's therapeutic benefits for metabolic syndrome (MetS) and its components.

Methods: The Comparative Toxicogenomics Database, MIENTURNET, Metascape, GeneMania, and Cytoscape software were critical analytic tools.

Results: Curcumin may have therapeutic effects on MetS and its components via the following genes: NOS3, IL6, INS, and ADIPOQ, particularly PPARG. Curcumin has higher docking scores than other genes with INS and PPARG (docking scores: -8.3 and -5.8, respectively). Physical interactions (56%) were found to be the most prevalent for dyslipidemia, co-expression for hypertension, obesity, T2DM, and MetS. "Galanin receptor pathway", "lipid particles composition", "IL-18 signaling pathway", "response to extracellular stimulus", and "insulin resistance" were listed in the first of the key pathways for MetS, dyslipidemia, hypertension, obesity, and diabetes, respectively. The protein-protein interaction enrichment analysis study also identified "vitamin B12 metabolism," "folate metabolism," and "selenium micronutrient network" as three major molecular pathways linked to MetS targeted by curcumin. PPARG was the key transcription factor that regulated practically all curcumin-targeted genes linked to MetS and its components. Curcumin targeted hsa-miR-155-5p, which has been linked to T2DM, hypertension, and MetS, as well as hsa-miR-130b-3p and hsa-miR-22-3p, which have been linked to dyslipidemia and obesity, respectively. In silico, sponges that regulated hsa-miR-155-5p were developed and evaluated. Curcumin, MetS, and its components have been found to target adipocytes, cardiac myocytes, smooth muscle, the liver, and pancreas. Curcumin's physicochemical properties and pharmacokinetics are closely connected with its therapeutic advantages in MetS and its components due to its high gastrointestinal absorption, drug-likeness, water solubility, and lipophilic nature. Curcumin is a CYP1A9 and CYP3A4 inhibitor. Although curcumin has a low bioavailability, it can be synthesized and administered to increase its pharmacokinetic features.

Conclusions: Curcumin needs to undergo therapeutic optimization and further study into its pharmacological structure before it can be used to treat MetS and its components.

Keywords: Curcumin; Genes and transcription factors; In silico; Metabolic syndrome; Molecular mechanisms; miRNA.