Abstract:
Curcumin diglutaric acid (CurDG), an ester prodrug of curcumin, has the potential to be
developed as an anti-inflammatory agent due to its improved solubility and stability. In this study,
the anti-inflammatory effects of CurDG were evaluated. The effects of CurDG on inflammatory
mediators were evaluated in LPS-stimulated RAW 264.7 macrophage cells. CurDG reduced the
increased levels of NO, IL-6, and TNF- α, as well as iNOS and COX-2 expression in cells to a greater
extent than those of curcumin, along with the potent inhibition of MAPK (ERK1/2, JNK, and p38)
activity. The anti-inflammatory effects were assessed in vivo by employing a carrageenan-induced
mouse paw edema model. Oral administration of CurDG demonstrated significant anti-inflammatory
effects in a dose-dependent manner in mice. The effects were significantly higher compared to those
of curcumin at the corresponding doses (p < 0.05). Moreover, 25 mg/kg curcumin did not exert a
significant anti-inflammatory effect for the overall time course as indicated by the area under the curve
data, while the equimolar dose of CurDG produced significant anti-inflammatory effects comparable
with 50, 100, and 200 mg/kg curcumin (p < 0.05). Similarly, CurDG significantly reduced the
proinflammatory cytokine expression in paw edema tissues compared to curcumin (p < 0.05). These
results provide the first experimental evidence for CurDG as a promising anti-inflammatory agent.
