Indicaxanthin from Cactus Pear Fruit Exerts Anti-Inflammatory Effects in Carrageenin-Induced Rat Pleurisy

Nutritional research has shifted recently from alleviating nutrient deficiencies to chronic disease prevention. We investigated the activity of indicaxanthin, a bioavailable phytochemical of the betalain class from the edible fruit of Opuntia ficus-indica (L. Miller) in a rat model of acute inflammation. Rat pleurisy was achieved by injection of 0.2 mL of lambda-carrageenin in the pleural cavity, and rats were killed 4, 24, and 48 h later; exudates were collected to analyze inflammatory parameters, such as nitric oxide (NO), prostaglandin E-2 (PGE(2)), interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha); cells recruited in pleura were analyzed for cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) expression, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) activation. Indicaxanthin (0.5, 1, or 2 mu mol/kg), given orally before carrageenin, time- and dose-dependently, reduced the exudate volume (up to 70%) and the number of leukocytes recruited in the pleural cavity (up to 95%) at 24 h. Pretreatment with indicaxanthin at 2 mu mol/kg inhibited the carrageenin-induced release of PGE(2) (91.4%), NO (67.7%), IL-1 beta (53.6%), and TNF-alpha (71.1%), and caused a decrease of IL-1 beta (34.5%), TNF-alpha (81.6%), iNOS (75.2%), and COX2 (87.7%) mRNA, as well as iNOS (71.9%) and COX-2 (65.9%) protein expression, in the recruited leukocytes. Indicaxanthin inhibited time- and dose-dependently the activation of NF-kappa B, a key transcription factor in the whole inflammatory cascade. A pharmacokinetic study with a single 2 mu mol/kg oral administration showed a maximum 0.22 +/- 0.02,mu mol/L (n= 15) plasma concentration of indicaxanthin, with a half-life of 1.15 +/- 0.11 h. When considering the high bioavailability of indicaxanthin in humans, our findings suggest that this dietary pigment has the potential to improve health and prevent inflammation-based disorders.