The 3 Curcuminoid Analogs Comprising the Curcumin Extract Comparably Inhibit Nuclear Factor kappa-light-chain-enhancer Activation

Introduction: The curcumin extract, although relatively isolated from the rest of the plant’s constituents, still exhibits an expansive polypharmacology. The extract is made up of 3 main curcuminoid analogs: diferuloylmethane (curcumin I), desmethoxycurcumin (curcumin II), and bisdesmethoxycurcumin (curcumin III). Each curcuminoid analog displays homologous structure with slight differences that should contribute to differential pharmacology. The study of these curcuminoids in isolation using different subcellular targets and cell lines may help us better understand the mechanisms involved in the curcumin extract’s total polypharmacology. This research can also help us determine how the pharmacology of these curcuminoid analogs might be used with greater drug-target selectivity. Methods/Results: As a start to this lengthy process, process a human embryonic kidney cell line containing the SV40 T-antigen (HEK293T) cell line is chosen for transfection with a basic Nuclear Factor kappa-light-chain-enhancer (NF-kB) reporter plasmid to study, by luciferase assay, the inhibitive potential of the curcuminoids in isolation. All 3 curcuminoids are shown here to inhibit p65–p50 (one of the NF-kB family protein complexes) activation in tumor necrosis factor (TNFα)–stimulated HEK293T cells with a comparable level of inhibitive activity. Each of the 3 curcuminoids exhibits the same IC50 (concentration of an inhibitor to half the activity) in 2 different curcuminoid contexts studied with regard to NF-kB inhibition. Conclusion: We will continue to study these curcuminoid analogs with a cautious expectation that they will exhibit differential pharmacology with respect to alternative targets we will study. However, with regards to NF-kB inhibition, the three structurally different curcuminoids exhibit similar pharmacology.