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

Abstract

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 λ-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-1β (IL-1β), and tumor necrosis factor-α (TNF-α); cells recruited in pleura were analyzed for cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) expression, and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activation. Indicaxanthin (0.5, 1, or 2 μmol/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 μmol/kg inhibited the carrageenin-induced release of PGE(2) (91.4%), NO (67.7%), IL-1β (53.6%), and TNF-α (71.1%), and caused a decrease of IL-1β (34.5%), TNF-α (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-κB, a key transcription factor in the whole inflammatory cascade. A pharmacokinetic study with a single 2 μmol/kg oral administration showed a maximum 0.22 ± 0.02 μmol/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.

Indicaxanthin Dietetics: Past, Present, and Future

“…All this appears consistent with the antioxidant activity observed in simple chemical systems such as soybean phosphatidylcholine (PC) bilayers [28]. In addition, interactions of indicaxanthin with membrane lipids and possibly other components, could elicit cell responses, and account for cell effects of indicaxanthin, including anti-inflammatory and anti-apoptotic effects [38][39][40]. …”

“…Remarkable anti-inflammatory effects have been observed in a carrageenininduced rat pleurisy model [39]. Orally given to the extent of 8 µmol/kg, which is consistent with a human dietary assumption from cactus pear fruits [36], prior to carrageenin injection in the pleural cavity, indicaxanthin caused a 72 % reduction of the inflammatory exudate volume, and 95 % reduction of total leukocyte number.…”

“…Moreover, its redox chemistry and physicochemical characteristics [21,29] allow the molecule to interact with membranes [34], penetrate cells [32] and scavenge both lipid radicals and water-soluble oxidants [28,35]. So far, evidence of anti-apoptotic [40] and immune-modulator [103] activity has been provided, and capacity of indicaxanthin of reverting epigenetic changes associated with cancer development [111] shown in in vitro models, whereas only one study reported on anti-inflammatory effects in rat [39]. Future investigations in animal models, and characterization of indicaxanthin from a "nutri-epigenomic perspective," will provide important information on the potential to act as a chemopreventive agent.…”

Mediterranean Diet and Healthy Ageing: A Sicilian Perspective

“…Table 1 reports a brief description of some foods characterizing Sicilian countryside dietary habits [27,28,29,30,31,32]. As previously stated, olive oil plays a central role in MedDiet [2,11,33,34,35] and a glass of wine with meals may be assumed every day [2,11].…”

Phytochemical Indicaxanthin Inhibits Colon Cancer Cell Growth and Affects the DNA Methylation Status by Influencing Epigenetically Modifying Enzyme Expression and Activity

“…In recent years, the properties and bioactivities of indicaxanthin (Ind), a betalain highly concentrated in the cactus pear fruit, have been researched [15]. This molecule can behave as a radical scavenger and antioxidant [16,17,18], possesses physico-chemical characteristics allowing its interaction with and location in membranes [19], and shows anti-inflammatory activity in in vitro and in vivo models [20,21,22]. Ind has been shown to be stable under digestive conditions and is not metabolized by enterocytes, therefore being highly bioavailable in the gut in its native form [23].…”