Nanocurcumin attenuates inflammation by decreasing Toll‐like receptor 2 and 4 expression and activity and promoting an anti‐inflammatory macrophage phenotype (830.22)

Abstract

Curcumin, the yellow polyphenol extracted from turmeric (Curcuma longa), has potent anti‐inflammatory properties. However, due to poor aqueous solubility and thus limited systemic bioavailability, it has not been used clinically. Nanoparticle‐based drug delivery approaches have the potential for rendering hydrophobic agents like curcumin dispersible in aqueous media. We have synthesized a polymeric nanoparticle encapsulated curcumin ‐ nanocurcumin (NC) and have shown that it is readily dispersed in aqueous media and demonstrates comparable in vitro therapeutic efficacy to free curcumin. Obesity and diabetes are pro‐inflammatory states characterized by increased monocyte Toll like receptors (TLR) 2 and 4 and a propensity to a M1 pro‐inflammatory phenotype. In this study, we aimed to examine the effects of NC on monocyte TLR2 and 4 expression and activity and on macrophage phenotype and subsequent inflammatory pathways. Incubation of monocytes with NC (5uM) compared to vehicle control resulted in 50% inhibition of TLR2 and 60% inhibition of TLR4 expression, a 35% reduction in downstream signaling, ie. MyD88 expression and NFKb activity. Furthermore, incubation with NC resulted in conversion of macrophages from M1 to M2 phenotype. All of these beneficial effects of NC led to a significant downregulation of several pro‐inflammatory cytokines and chemokines (IL‐6, IL‐8, MCP‐1 and TNFα). These studies suggest that NC could be a potent adjunctive anti‐inflammatory therapeutic strategy to consider in vivo, especially in obesity and diabetes.