Augmented cAMP Signaling by Co-Administration of Resvera-trol and Curcumin: A Cellular Biosensor Kinetic Assessment

Abstract

Curcumin and resveratrol are two polyphenolic compounds extensively investigated for their medicinal effects on inflammatory signaling. However, there is a paucity of information on the Adenosine-3', 5'-cyclic monophosphate (cAMP) kinetics following administration of curcumin and resveratrol in biological systems. In this study, kinetic modulation of cAMP as a target detection messenger in pro-inflammatory pathways was assessed by co-administration of curcumin and resveratrol using a cellular sensor model. To evaluate their putative activity, curcumin and resveratrol compounds were administered alone or in combination on the media culture of cAMP EPAC (exchange protein directly activated by cAMP) bioluminescence resonance energy transfer (BRET) biosensor. The study was performed at the following two centers at Tehran University of Medical Sciences (TUMS): 1- Biotechnology Research Center, and, 2- Endocrinology and Metabolism Research Institute (EMRI) in 2017. Time course kinetic of cAMP response signals were plotted. Forskolin and IBMX were used to stabilize the cAMP signals. When we treated HEK-293T biosensor cells at 10uM concentration, curcumin and resveratrol upregulated cAMP signaling. Co-administration of resveratrol and curcumin revealed an augmented cAMP level, as compared to treatments with the compounds alone. Co-administration of curcumin and resveratrol leverage cAMP kinetic response in a time-course manner. The presented methodology can be readily adopted for drug development and novel biopharmaceutical functional analyses.