Dimethoxycurcumin, a metabolically stable analogue of curcumin, exhibits anti-inflammatory activities in murine and human lymphocytes

The aim of this study was to investigate whether dimethoxycurcumin (DiMC), a synthetic curcumin analogue having higher metabolic stability over curcumin, could exhibit anti-inflammatory activity in murine and human lymphocytes. Both curcumin and DiMC suppressed mitogen as well as antigen driven proliferation of murine splenic lymphocytes. Further, mitogen and antigen-stimulated cytokine (IL-2, IL-4, IL-6 and IFN-γ) secretion by T cells was also abrogated by curcumin and DiMC. Interestingly, curcumin and DiMC suppressed B cell proliferation induced by lipopolysaccharide. Curcumin and DiMC also inhibited Con A-induced activation of early and late T cell activation markers. They scavenged basal Reactive Oxygen Species and depleted GSH levels in lymphocytes. The suppression of mitogen-induced T cell proliferation and cytokine secretion by curcumin and DiMC was significantly abrogated by thiol containing antioxidants suggesting a role for redox in their anti-inflammatory activity. Further, the possibility of curcumin and DiMC directly interacting with thiol-containing antioxidant GSH was monitored by changes in absorbance. Both curcumin and DiMC inhibited Con A induced activation of NF-κB and MAPK. More importantly, curcumin and DiMC inhibited phytohaemagglutinin induced proliferation and cytokine secretion by human peripheral blood mononuclear cells. To explore their therapeutic efficacy, they were added to lymphocytes post-Con A stimulation and we observed a significant suppression of IL-2, IL-6 and IFN-γ. The present study for the first time demonstrates the potent anti-inflammatory activity of DiMC. Further, DiMC could find application as an alternative to curcumin, which is currently used in several clinical studies, due to its superior bioavailability and comparable efficacy.