Article

Inhibitory effects of indicaxanthin on mouse ileal contractility: Analysis of the mechanism of action

Dipartimento di Biologia cellulare e dello Sviluppo, Università di Palermo, 90128 Palermo, Italy.
European journal of pharmacology (Impact Factor: 2.53). 02/2011; 658(2-3):200-5. DOI: 10.1016/j.ejphar.2011.02.034
Source: PubMed

ABSTRACT

Recently, we have showed that indicaxanthin, the yellow betalain pigment abundant in the fruit of Opuntia ficus indica, has remarkable spasmolytic effects on the intestinal contractility in vitro. Thus, the purpose of the present study was to investigate the mechanism of action underlying the observed response. We used organ bath technique to record the mechanical activity of the mouse ileum longitudinal muscle and ELISA to measure the levels of cAMP. Indicaxanthin induced inhibitory effects on spontaneous mechanical activity, which were unaffected by indomethacin, a non-selective inhibitor of cycloxygenase; 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a selective inhibitor of nitric oxide-dependent guanylyl cyclase; 2'5'dideoxyadenosine, an adenylyl cyclase inhibitor; and zaprinast, a selective inhibitor of the cGMP phosphodiesterase isoenzyme. Indicaxanthin effects were reduced significantly in the presence of 3-isobutyl-1-methylxanthine (IBMX), a non selective inhibitor of phosphodiesterases (PDEs). Indicaxanthin and IBMX significantly reduced the carbachol-evoked contractions and the joint application of both drugs did not produce any additive effect. Indicaxanthin and IBMX increased the inhibitory effects of forskolin, an adenylyl cyclase activator, and the joint application of both drugs did not produce any additive effect. Indicaxanthin, contrarily to IBMX, did not affect the inhibitory action of sodium nitroprusside, a soluble guanylyl cyclase activator. Indicaxanthin increased both basal and forskolin-induced cAMP content of mouse ileal muscle. The present data show that indicaxanthin reduces the contractility of ileal longitudinal muscle by inhibition of PDEs and increase of cAMP concentration and raise the possibility of using indicaxanthin in the treatment of motility disorders, such as abdominal cramps.

Download full-text

Full-text

Available from: Flavia Mulè, Apr 14, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: 7-Ketocholesterol (7-KC)-induced apoptosis of macrophages is considered a key event in the development of human atheromas. In the present study, the effect of indicaxanthin (Ind), a bioactive pigment from cactus pear fruit, on 7-KC-induced apoptosis of human monocyte/macrophage THP-1 cells was investigated. A pathophysiological condition was simulated by using amounts of 7-KC that can be reached in human atheromatous plaque. Ind was assayed within a micromolar concentration range, consistent with its plasma level after dietary supplementation with cactus pear fruit. Pro-apoptotic effects of 7-KC were assessed by cell cycle arrest, exposure of phosphatidylserine at the plasma membrane, variation of nuclear morphology, decrease of mitochondrial trans-membrane potential, activation of Bcl-2 antagonist of cell death and poly(ADP-ribose) polymerase-1 cleavage. Kinetic measurements within 24 h showed early formation of intracellular reactive oxygen species over basal levels, preceding NADPH oxidase-4 (NOX-4) over-expression and elevation of cytosolic Ca2+, with progressive depletion of total thiols. 7-KC-dependent activation of the redox-sensitive NF-κB was observed. Co-incubation of 2·5 μm of Ind completely prevented 7-KC-induced pro-apoptotic events. The effects of Ind may be ascribed to inhibition of NOX-4 basal activity and over-expression, inhibition of NF-κB activation, maintaining cell redox balance and Ca homeostasis, with prevention of mitochondrial damage and consequently apoptosis. The findings suggest that Ind, a highly bioavailable dietary phytochemical, may exert protective effects against atherogenetic toxicity of 7-KC at a concentration of nutritional interest.
    No preview · Article · Dec 2012 · The British journal of nutrition
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Betalains are a family of natural pigments present in most plants of the order Caryophyllales. They provide colors ranging from yellow to violet to structures that in other plants are colored by anthocyanins. These include edible fruits and roots but also flowers, stems, and bracts. The recent characterization of different bioactivities in experiments with betalain-containing extracts and purified pigments has renewed the interest of the research community in these molecules used by the food industry as natural colorants. Studies with multiple cancer cell lines have demonstrated a high chemopreventive potential that finds in vitro support in a strong antiradical and antioxidant activity. Experiments in vivo with model animals and bioavailability studies reinforce the possible role played by betalains in the diet. This work provides a critical review of all the claimed biological activities of betalains, showing that the bioactivities described might be supported by the high antiradical capacity of their structural unit, betalamic acid. Although more investigations with purified compounds are needed, the current evidences suggest a strong health-promoting potential.
    No preview · Article · Aug 2014 · Critical Reviews in Food Science and Nutrition
  • [Show abstract] [Hide abstract]
    ABSTRACT: The betalamic acid derivatives of betalain pigments (purple-red betacyanins and yellow betaxanthins) are dietary compounds occurring in a few plant foods including beets (Beta vulgaris) and cactus pears (Opuntia spp.). Belonging to betaxanthins, indicaxanthin is rich in yellow cactus pear (Opuntia ficus indica L., Mill). High dietary bioavailability of indicaxanthin in humans, as well as its physicochemical properties, radical-scavenging and antioxidant activities in various experimental models suggest this molecule as a promising nutraceutical agent and open perspectives for its applications. Life-long modulatory activity at the epigenetic level now appears as the new frontier to shed light on the beneficial effects from a chronic exposure at dietary concentrations of redox-active phytochemicals. Data obtained from studies on human intestinal carcinoma cell cultures show that indicaxanthin has the potential to affect global DNA methylation, revert onco-suppressor gene silencing, and induce arrest of cell growth. Elucidation of cell pathways and molecular mechanisms underlying epigenetic activities in various cells and conditions is needed to understand these benefits and limitations of dietary indicaxanthin.
    No preview · Article · Jan 2015