Franco Cavaleri, Ph.D candidate Biologic Pharmamedical Research Surrey, BC CANADA
IN PEER-REVIEW AWAITING PUBLICATION
Curcumin has been used successfully to treat inflammatory conditions, however, reliability and repeatability of clinical and bench research results have been a challenge. Curcumin is comprised of three curcuminoid analogues that can vary in proportion from one extract to another. A better understanding of how each curcuminoid analogue of the curcumin extract can partake in the overall curcumin pharmacology might give us better insight on the polypharmacology involved. All three curcuminoids: curcumin I (diferuloylmethane), curcumin II (demethoxycurcumin) and curcumin III (bisdemthoxycurcumin), are shown here to modulate three key subcellular drug targets differentially. At a nuclear level, multiple compounding findings related to curcumin pharmacology, regulate transactivation of the NF-kB heterodimer once it has translocated. Each of the three curcuminoid analogues appear to inhibit phosphorylation of p65 at residue serine 276 with Curcumin I showing a significant hindrance. On the other hand, curcumin III and not curcumins I or II is found to significantly downregulate Mitogen- and stress-activated protein kinase 1 status in the cytosol and nucleus. The upstream mechanism repressing MSK1 status is also shown to be the upregulation of MIR 148a by curcumin III. Curcumin II shows down-regulatory activity of MIR 148a in opposition to curcumin III’s up-regulatory activity. These results demonstrate that although there are some common targets by the curcuminoid analogues, a differential activity by each can also be observed on other targets. These new findings show us that the common curcumin extract can be utilised with greater selectivity against specific drug targets and the associated disease pathology.
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