Curcumin analogues suppress cellular pro-inflammatory mediators and reduce edema

Inflammation is a normal physiological response to adverse stimuli mediated by numerous pro-inflammatory cytokines and signaling pathways. Although curcumin modulates key inflammatory pathways, the role of its analogues in inflammation is not fully elucidated. This study explores the anti-inflammatory potential of curcumin analogues (K1-K4) in vitro and in vivo models. Four curcumin analogues (K1-K4) were successfully synthesized and assessed for their anti-inflammatory efficacy at doses of 10 and 20 mg/kg body weight. All the curcumin analogues, particularly K1 and K4 demonstrated significant attenuation of absolute post-injection carrageenan-induced paw edema in mice, exhibiting a significant response at both doses. The maximum inhibition of paw edema was achieved after 2 h, i.e., 62.45% for K1 and 62.09% for K4 at a dose of 20 mg/kg compared to diclofenac (66.10%). The analogues markedly ameliorated ear edema and prominently alleviated the absolute post-injection paw edema mediated by histamine in mice. Among the analogues, K1 and K4 exhibited the highest activity and markedly attenuated the edema in all models. Mechanistically, the curcumin analogues except K2 significantly downregulated iNOS, COX2, and p-p65 protein levels in RAW264.7 cells. The mRNA expression of inflammatory cytokines was also notably diminished in RAW264.7 cells. Moreover, K1 was observed to affect markers associated with apoptosis among the curcumin analogues. The findings demonstrate that curcumin analogues suppress key pro-inflammatory mediators in cells and reduce edema in vivo, highlighting their preliminary anti-inflammatory activity in acute inflammation models.