Different curcuminoids inhibit T-lymphocyte proliferation independently of their radical scavenging activities

Purpose. We investigated the inhibitory effects of curcumin, curcumin derivatives and degradation products on OKT3-induced human peripheral blood mononuclear cell (PBMC) proliferation and the role of their radical scavenging activity. Methods. OKT3-induced human PBMC proliferation was determined by measuring (3)H-thymidine incorporation. Radical scavenging activity was evaluated by using an in vitro DPPH assay. Results. OKT3-induced PBMC proliferation was inhibited by curcumin, isocurcumin, bisdesmethoxy-, diacetyl-, tetrahydro-, hexahydro-, and octahydrocurcumin as well as by vanillin, ferulic acid, and dihydroferulic acid with IC(50)-values of 2.8, 2.8, 6.4, 1.0, 25, 38, 82, 729, 457, and > 1,000 mu M, respectively. The investigated substances with the strongest effect on radical scavenging were tetrahydro-, hexahydro-, and octahydrocurcumin with IC(50) values of 10.0, 11.7, and 12.3 mu M, respectively. IC(50)-values of dihydroferulic acid, ferulic acid, and curcumin were 19.5, 37, and 40 mu M. The substances with the lowest radical scavenging activities were vanillin, isocurcumin, diacetylcurcumin, and bisdesmethoxycurcumin with IC(50) values higher than 100 mu M each. Conclusions. Curcuminoid-induced inhibition of OKT3-induced PBMC proliferation depends on the number of carbon atoms and double bonds of the 1,6-heptadiene-3,5-dione structure as well as on the phenolic ring substitutes of the curcuminoids but is not correlated to their respective radical scavenging activity.