Diacetylcurcumin: Its Potential Antiarthritic Effect on a Freund's Complete Adjuvant-Induced Murine Model

Abstract

The present study aims to evaluate the antiarthritic activity of diacetylcurcumin (DAC), a synthetic derivative where the free phenolic groups of curcumin are derivatized by acetylation, thereby conferring greater lipophilicity to the parent molecule and partially overcoming the limited systemic bioavailability of curcumin. Antiarthritic activity was evaluated on a Freund's complete adjuvant (FCA)-induced murine model of arthritis. Oral administration of DAC (60 and 120 mg/kg) resulted in a significant inhibition of inflammation in the acute and chronic phases, respectively, demonstrating an improved and sustained anti-inflammatory effect, comparable to that of curcumin (150 mg/kg) in the chronic stage at a lower dose. Phenylbutazone (80 mg/kg) was used as a reference drug. The pharmacological consequence of DAC or curcumin treatment is the prevention of secondary lesions commonly associated with this biological model.

Keywords: Freund’s complete adjuvant; antiarthritic; curcumin; diacetylcurcumin.

Figure 1

Acute effect of the oral administration of phenylbutazone (80 mg/kg), (A) curcumin, and (B) diacetylcurcumin (DAC) (60, 120, and 150 mg/kg) on the edema produced by intradermal injection of Freund’s complete adjuvant into the footpad of right rear limbs of Wistar rats. Each bar represents the mean ± SEM (n = 5). ANOVA followed by Tukey’s test. p < 0.05, 0.01 and 0.001 (*, ** and *** respectively).

Figure 2

Antiinflammatory effect during the chronic phase of the oral administration of phenylbutazone (80 mg/kg), (A) curcumin, and (B) diacetylcurcumin (DAC) (60, 120, and 150 mg/kg) upon the edema induced by intradermal injection of Freund’s complete adjuvant into the footpad of right rear limbs of Wistar rats. Each point represents the mean ± SEM (n = 5). ANOVA followed by Tukey’s test. p < 0.05, 0.01 and 0.001 (*, ** and *** respectively).

Figure 3

Edema status after oral treatment (on day 25) with curcumin at different doses. (A) Vehicle, (B) Curcumin 60 mg/kg, (C) Curcumin 120 mg/kg, (D) Curcumin 150 mg/kg, and Phenylbutazone (80 mg/kg) (E).

Figure 4

Edema status after oral treatment (on day 25) with diacetylcurcumin (DAC) at different doses. (A) Vehicle, (B) DAC 60 mg/kg, (C) DAC 120 mg/kg, (D) DAC 150 mg/kg and Phenylbutazone (80 mg/kg) (E).

Figure 5

Chromatogram of the curcumin (1) (t_R = 4.873 min) sample, injected at a concentration of 0.25 mg/mL, with detection at a wavelength of 265 nm.

Figure 6

Chromatogram of diacetylcurcumin (2) (t_R = 9.190 min) samples, injected at a concentration of 0.25 mg/mL, with detection at a wavelength of 257 nm.