Inhibitory effects of 7,7'-bromo-curcumin on 12-O-tetradecanoylphorbol-13-acetate-induced skin inflammation

Eur J Pharmacol. 2019 Sep 5:858:172479. doi: 10.1016/j.ejphar.2019.172479. Epub 2019 Jun 20.

Abstract

This study aimed to determine the capacity of 7,7'-bromo-curcumin (CUR-Br), a curcumin analogue with higher chemical stability than curcumin (CUR), in the suppression of mouse ear edema. Male CD-1 mice were topically pre-treated with either CUR or CUR-Br for 30 min prior to an application of 12-O-tetradecanoylphorbol-13-acetate. After 6 h, mice were killed, and ear punches were measured for their weight and thickness as a marker of edema and inflammation. CUR-Br demonstrated a higher anti-inflammatory efficacy compared to CUR. CUR and CUR-Br at 1.0 μmol suppressed the TPA-induced increase in the ear weight by 26.0% and 57.2%, and decreased TPA-induced increase in the ear thickness by 22.2% and 84.7%, respectively. The inhibitory effects of Cur-Br were associated with decreased levels of inflammatory cytokines (IL-1β, IL-2, IL-6, KC/GRO, IL-10, IL-17, and IL-23). In addition, CUR-Br significantly downregulated expression of pro-inflammatory signaling proteins such as p-STAT3, STAT3, PI3K, AKT, p-p65, and COX-2. Overall, our results demonstrated that the curcumin analogue, CUR-Br, showed stronger anti-inflammatory properties than CUR in inhibiting TPA-induced inflammatory response in mouse skin.

Keywords: 7,7′-bromo-curcumin; Anti-inflammation; Curcumin analogue; Inflammatory cytokine; Stability; TPA-Induced ear edema.

MeSH terms

  • Animals
  • Curcumin / chemistry
  • Curcumin / pharmacology*
  • Curcumin / therapeutic use
  • Cytokines / metabolism
  • Edema / drug therapy
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / pathology
  • Male
  • Mice
  • NF-kappa B / metabolism
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects
  • Skin / drug effects*
  • Skin / metabolism
  • Skin / pathology
  • Structure-Activity Relationship
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Tetradecanoylphorbol Acetate / therapeutic use

Substances

  • Cytokines
  • NF-kappa B
  • STAT3 Transcription Factor
  • Curcumin
  • Tetradecanoylphorbol Acetate