In Silico Discovery of Green Tea and Green Coffee Bioactive Compounds Against IGF-1R, PPAR-α, and TLR4 as a Therapeutic Candidate for Metabolic Disorder

Abstract

Metabolic syndrome (MetS) affects millions of people globally since it is linked to multiple risk factors, including obesity, dyslipidemia, high blood pressure, and type 2 diabetes mellitus (T2DM). Several molecular factors are contributing to MetS developments, including insulin-like growth factor-1 receptor (IGF-1R), peroxisome proliferator-activated receptor α (PPAR-α), and Toll-like receptor-4 (TLR4). Green tea (GT) and green coffee (GC) have unique flavors due to their bioactive compounds, which act as antioxidants, anti-inflammatories, and antihypertension. This work aimed to examine the pathways implicated in the development of MetS and discover bioactive chemicals contained in GT and GC that have promising as inhibitors of IGF-1R, PPARα, and TLR4. The protein-protein interaction was explored using STRING, and the roles of bioactive compounds were evaluated in STITCH. The interaction between (-)-epigallocatechin (EC), catechin gallate (CG), epicatechin (EC), epigallocatechin gallate (EGCG), theobromine, trigonelline, chlorogenic acid, and caffeic acid against IGF-1R, PPAR-α, and TLR4 was measured by molecular docking. The present result demonstrated that eight protein interactions are involved in Mets development. The molecular docking result demonstrated that EGCG from GT has the best binding affinity (kcal/mol) to IGF-1R (-9.1), PPAR-α (-9.5), and TLR4 (-6.5). In conclusion, bioactive compounds from GT were superior to GT through computational study. Both might be promising as anti-inflammatories and regulate the metabolism under MetS conditions.