A Novel Synthetic Mono-Carbonyl Analogue of Curcumin, A13, Exhibits Anti-Inflammatory Effects In vivo by Inhibition of Inflammatory Mediators

Abstract

Curcumin is a pleiotropic molecule against inflammatory related diseases. However, poor bioavailability greatly limits its application in clinic. Our previous study synthesized and evaluated a hydrosoluble mono-carbonyl analogue of curcumin, (2E,5E)-2,5-bis(4-(3-(dimethylamino)-propoxy)benzylidene)cyclopentanone (A13). In the present study, we further evaluated the anti-inflammatory effect of A13 in vivo. In lipopolysaccharide-challenged mice, pretreatment of A13 (15mg/kg, i.v.) attenuated the increase of plasma level of NO, TNF-α, and IL-6, significantly inhibited the increase of hepatic inflammatory gene transcription, and improved pulmonary damages. In addition, A13 (10 or 30mg/kg, i.p.) reduced vascular permeability in Institute of Cancer Research mice and inhibited pain reaction in chemically induced inflammatory models. Together, A13 exhibits anti-inflammatory activities both in vitro and in vivo by the inhibition of various inflammatory mediators.