Curcuminoid Compounds Inhibit MacrophageMigration Inhibitory Factor: In Silico Study forTheir Association to Anti-diabetic Potency

Diabetes mellitus is a health problem characterized by chronic inflammation causing complications in the cardiovascular, kidneys, eyes, and nervous system, with macrophage migration inhibitory factor (MIF) protein playing a crucial function in the inflammatory process chain. MIF has been known as a signaling protein involved in the development of type 1 and type 2 diabetes mellitus (DM). There are several studies indicating that the development of type 1 and type 2 DM is influenced by the accumulation of macrophages in tissues susceptible to diabetic injury or infection. Curcuminoids, the bioactive components in turmeric, are known for their ability to decrease inflammation. This in silico study is intended to analyze the potential anti- inflammatory effect of curcuminoid in DM, with a specific focus on how it may reduce proinflammatory signals through MIF. The investigation involved predicting physicochemical, pharmacokinetic and toxicity (ADMET) qualities for curcuminoids, followed by molecular docking simulations with MIF as the target protein. The ADMET results showed curcumin and bisdemethoxycurcumin had favorable properties, while dimethoxycurcumin exhibited undesirable traits like low VDss. Therefore, molecular docking simulations were performed using curcumin and bisdemethoxycurcumin as ligands. The molecular docking simulations indicated that curcumin has a negative binding affinity slightly lower than (S, R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1), a reference MIF inhibitor; and bisdemethoxycurcumin binds to MIF even stronger than ISO-1, with interacting MIF amino acids Lys 32, Ile 64 Asn 97, Pro 1, and Tyr 95. Hence, the curcumin and bisdemethoxycurcumin compounds were found as having the potential to inhibit MIF activity that is associated with the progression of DM.