Potential interaction of natural dietary bioactive compounds with COX-2.

Environmental and Computational Chemistry Group, University of Cartagena, Cartagena, Colombia.
Journal of molecular graphics & modelling (Impact Factor: 2.17). 07/2011; 30:157-66. DOI: 10.1016/j.jmgm.2011.07.002
Source: PubMed

ABSTRACT Bioactive natural products present in the diet play an important role in several biological processes, and many have been involved in the alleviation and control of inflammation-related diseases. These actions have been linked to both gene expression modulation of pro-inflammatory enzymes, such as cyclooxygenase 2 (COX-2), and to an action involving a direct inhibitory binding on this protein. In this study, several food-related compounds with known gene regulatory action on inflammation have been examined in silico as COX-2 ligands, utilizing AutoDock Vina, GOLD and Surflex-Dock (SYBYL) as docking protocols. Curcumin and all-trans retinoic acid presented the maximum absolute AutoDock Vina-derived binding affinities (9.3 kcal/mol), but genistein, apigenin, cyanidin, kaempferol, and docosahexaenoic acid, were close to this value. AutoDock Vina affinities and GOLD scores for several known COX-2 inhibitors significatively correlated with reported median inhibitory concentrations (R² = 0.462, P < 0.001 and R² = 0.238, P = 0.029, respectively), supporting the computational reliability of the predictions made by our docking simulations. Moreover, docking analysis insinuate the synergistic action of curcumin on celecoxib-induced inhibition of COX-2 may occur allosterically, as this natural compound docks to a place different from the inhibitor binding site. These results suggest that the anti-inflammatory properties of some food-derived molecules could be the result of their direct binding capabilities to COX-2, and this process can be modeled using protein-ligand docking methodologies.

1 Bookmark
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Natural compounds commonly found in foods may contribute to protect cells against the deleterious effects of inflammation. These anti-inflammatory properties have been linked to the modulation of transcription factors that control expression of inflammation-related genes, including the inducible nitric oxide synthase (iNOS), rather than a direct inhibitory action on these proteins. In this study, forty two natural dietary compounds, known for their ability to exert an inhibitory effect on the expression of iNOS, have been studied in silico as docking ligands on two available 3D structures for this protein (PDB ID: 3E7G and PDB ID: 1NSI). Natural compounds such as silibinin and cyanidin-3-rutinoside and other flavonoids showed the highest theoretical affinities for iNOS. Docking affinity values calculated for several known iNOS inhibitors significatively correlated with their reported half maximal inhibitory concentrations (R = 0.842, P < 0.0001), suggesting the computational reliability of the predictions made by our docking simulations. Moreover, docking affinity values for potent iNOS inhibitors are of similar magnitude to those obtained for some studied natural products. Results presented here indicate that, in addition to gene expression modulation of proteins involved in inflammation, some chemicals present in food may be acting by direct binding and possible inhibiting actions on iNOS.
    Molecules 12/2012; 17(7):8118-35. · 2.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Diet and health seem more important to the public than ever before. Proper nutrition from fruits and vegetables provide the source of beneficial phytochemicals, especially polyphenols. Accurate measurement of the antioxidant and anti-inflammatory properties of polyphenols is crucial to distributing the correct information. Measuring the raw plant material is useful, but not the whole picture. Upon ingestion, the body changes the polyphenols into new and unique structures, which are the biologically active compounds. This study includes extracts of various plant materials: green tea, black tea, green coffee, mango, tamarind, black carrot, and Lorogen, along with pure compounds: resveratrol, glutathione, and curcumin. The extracts and pure compounds, in vitro digestates, and in vivo rabbit plasma metabolites are compared by the FRAP and Folin antioxidant assays, along with albumin binding to describe the anti-inflammatory properties.
    09/2013, Supervisor: Dr. Joe Vinson
  • [Show abstract] [Hide abstract]
    ABSTRACT: : Mediators of anti-hypertensive actions of docosahexaenoic acid (DHA) are largely unknown. The omega-3 epoxide of DHA, 19, 20-EDP (epoxydocosapentaenoic acid) is metabolized by soluble epoxide hydrolase (sEH), which also metabolizes the anti-inflammatory and anti-hypertensive arachidonic acid (ARA) epoxides, EETs (epoxyeicosatrienoic acids). Based in part on plasma levels of EDPs following a DHA-rich diet, we hypothesized that 19, 20-EDP contributes to the anti-hypertensive actions of DHA in angiotensin-II dependent hypertension. Treatment individually with 19, 20-EDP, and a potent sEH inhibitor (sEHI) TPPU (1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea) significantly lowered blood pressure (BP) as compared to angiotensin-II infused animals. The largest reduction in BP was obtained with the combination of 19, 20-EDP and TPPU, which was more efficacious than the combination of 14, 15-EET and TPPU. Oxylipin profiling revealed that 19, 20-EDP and 14, 15-EET infusion affected mostly metabolites of the P450 pathway but also renal levels of prostaglandin-E2. Our findings suggest that 19, 20- EDP is a mediator of the anti-hypertensive effects of DHA in angiotensin-II dependent hypertension. It appears that 19, 20- EDP requires metabolic stabilization with a sEHI to be most effective in lowering BP, although both TPPU and 19, 20- EDP are so effective on their own that demonstrating additive or synergistic interactions is difficult.
    Journal of cardiovascular pharmacology 03/2014; · 2.83 Impact Factor

Similar Publications