Antiglucocorticoid potential of nutraceuticals: In silico molecular docking and in vitro assessment

Glucocorticoid hormones are known for their diabetogenic effects. We explored the antiglucocorticoid potential of andrographolide, curcumin, diosgenin, ellagic acid, genistein, gibberellin A3, kaempferol, quercetin, resveratrol, and silibinin using molecular docking simulations and cell‐based studies. Docking simulations accurately predicted the binding pose of mifepristone as revealed by appreciable superimposition of predicted pose with that of the crystal data. With the exception of diosgenin, all tested nutraceuticals were predicted to occupy the inhibitor site on glucocorticoid receptor in silico. Cell‐based studies performed with H4‐IIE‐C3 cells revealed that curcumin, genistein, kaempferol, and quercetin possess the propensity to antagonize dexamethasone‐induction of tyrosine aminotransferase activity. Our work suggests that curcumin, genistein, kaempferol, and quercetin exhibit antiglucocorticoid activity in vitro. Practical applications This work shows that curcumin, genistein, kaempferol, and quercetin exhibit antiglucocorticoid activity, although it remains to be understood whether the antagonism reported here is mediated by direct interaction with the receptor or due to secondary mechanisms. Our work establishes the basis for exploring the relevance of glucocorticoid antagonism in antidiabetic potential of curcumin, genistein, kaempeferol, and quercetin in vivo. Our work also provides a scientific rationale for utilizing curcumin, genistein, kaempeferol, and quercetin as ingredients for development of functional foods for dietary management of type 2 diabetes.