Anti-proliferative, anti-inflammatory and antioxidant effects of curcumin analogue A₂

In the present study, we determined the anti-proliferative, anti-inflammatory and antioxidant effects of a curcumin analogue, 2,6-bis(3,4-dihydroxybenzylidene) cyclohexanone (designated as A2). In vitro studies showed that A2 had a stronger inhibitory effect on the growth of mouse macrophage RAW 264.7 cells than curcumin. A2 also showed a stronger inhibitory effect than curcumin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced increases in NF-κB activation and IL-1β expression as well as in aldose reductase activity. A2 was a stronger antioxidant than curcumin as determined by inhibition of lipid peroxidation, inhibition of 1,1-diphenyl-2-picryl-hydrazyl free radical formation, and inhibition of 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical formation. In vivo studies indicated that A2 was more potent than curcumin for inhibiting TPA-induced ear edema and TPA-induced increases in IL-1β. In addition, oral administration of A2 at a dose of 2,000 mg/kg body weight did not cause acute toxicity in mice. Taken together, the results of our study indicate that the curcumin analogue A2 has stronger anti-proliferative, anti-inflammatory and antioxidant activities than curcumin.