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      Curcumin: An Anti-Inflammatory Molecule from a Curry Spice on the Path to Cancer Treatment

      review-article
      * ,
      Molecules
      MDPI
      curcumin, cancer, anti-oxidant, anti-inflammatory, nanoparticles

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          Abstract

          Oxidative damage and inflammation have been pointed out in preclinical studies as the root cause of cancer and other chronic diseases such as diabetes, hypertension, Alzheimer’s disease, etc. Epidemiological and clinical studies have suggested that cancer could be prevented or significantly reduced by treatment with anti-oxidant and anti-inflammatory drugs, therefore, curcumin, a principal component of turmeric (a curry spice) showing strong anti-oxidant and anti-inflammatory activities, might be a potential candidate for the prevention and/or treatment of cancer and other chronic diseases. However, curcumin, a highly pleiotropic molecule with an excellent safety profile targeting multiple diseases with strong evidence on the molecular level, could not achieve its optimum therapeutic outcome in past clinical trials, largely due to its low solubility and poor bioavailability. Curcumin can be developed as a therapeutic drug through improvement in formulation properties or delivery systems, enabling its enhanced absorption and cellular uptake. This review mainly focuses on the anti-inflammatory potential of curcumin and recent developments in dosage form and nanoparticulate delivery systems with the possibilities of therapeutic application of curcumin for the prevention and/or treatment of cancer.

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          Most cited references120

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          The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta.

          NF-kappaB comprises a family of cellular transcription factors that are involved in the inducible expression of a variety of cellular genes that regulate the inflammatory response. NF-kappaB is sequestered in the cytoplasm by inhibitory proteins, I(kappa)B, which are phosphorylated by a cellular kinase complex known as IKK. IKK is made up of two kinases, IKK-alpha and IKK-beta, which phosphorylate I(kappa)B, leading to its degradation and translocation of NF-kappaB to the nucleus. IKK kinase activity is stimulated when cells are exposed to the cytokine TNF-alpha or by overexpression of the cellular kinases MEKK1 and NIK. Here we demonstrate that the anti-inflammatory agents aspirin and sodium salicylate specifically inhibit IKK-beta activity in vitro and in vivo. The mechanism of aspirin and sodium salicylate inhibition is due to binding of these agents to IKK-beta to reduce ATP binding. Our results indicate that the anti-inflammatory properties of aspirin and salicylate are mediated in part by their specific inhibition of IKK-beta, thereby preventing activation by NF-kappaB of genes involved in the pathogenesis of the inflammatory response.
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            The role of cyclooxygenases in inflammation, cancer, and development.

            The cyclooxygenase (COX) enzymes catalyze a key step in the conversion of arachidonate to PGH2, the immediate substrate for a series of cell specific prostaglandin and thromboxane synthases. Prostaglandins play critical roles in numerous biologic processes, including the regulation of immune function, kidney development, reproductive biology, and gastrointestinal integrity. There are two COX isoforms, which differ mainly in their pattern of expression. COX-1 is expressed in most tissues, whereas COX-2 usually is absent, but is induced by numerous physiologic stimuli. Surprisingly, disruption of Cox1 (Ptgs1) in the mouse did not result in gastrointestinal abnormalities. cox-2 (Ptgs2) null mice show reproductive anomalies and defects in kidney development. Epidemiologic, animal, and human data indicate that NSAIDs, inhibitors of cyclooxygenase, are chemopreventive for colon cancer. COX-2 is overexpressed in 50% of benign polyps and 80-85% of adenocarcinomas. Offspring from cox-2 null by Apcdelta716 matings exhibit an 86% reduction in polyp number when compared to offspring from control animals, thus providing genetic evidence that COX-2 contributes to tumor formation or growth. The in vivo mechanism by which COX-2 affects tumor growth has not been determined. It is possible that both tumor and stromally derived COX-2 could influence tumor angiogenesis and/ or immune function.
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              Curcumin nanoparticles: preparation, characterization, and antimicrobial study.

              Curcumin is a highly potent, nontoxic, bioactive agent found in turmeric and has been known for centuries as a household remedy to many ailments. The only disadvantage that it suffers is of low aqueous solubility and poor bioavailability. The aim of the present study was to develop a method for the preparation of nanoparticles of curcumin with a view to improve its aqueous-phase solubility and examine the effect on its antimicrobial properties. Nanoparticles of curcumin (nanocurcumin) were prepared by a process based on a wet-milling technique and were found to have a narrow particle size distribution in the range of 2-40 nm. Unlike curcumin, nanocurcumin was found to be freely dispersible in water in the absence of any surfactants. The chemical structure of nanocurcumin was the same as that of curcumin, and there was no modification during nanoparticle preparation. A minimum inhibitory concentration of nanocurcumin was determined for a variety of bacterial and fungal strains and was compared to that of curcumin. It was found that the aqueous dispersion of nanocurcumin was much more effective than curcumin against Staphylococcus aureus , Bacillus subtilis , Escherichia coli , Pseudomonas aeruginosa , Penicillium notatum , and Aspergillus niger . The results demonstrated that the water solubility and antimicrobial activity of curcumin markedly improved by particle size reduction up to the nano range. For the selected microorganisms, the activity of nanocurcumin was more pronounced against Gram-positive bacteria than Gram-negative bacteria. Furthermore, its antibacterial activity was much better than antifungal activity. The mechanism of antibacterial action of curcumin nanoparticles was investigated by transmission electron micrograph (TEM) analysis, which revealed that these particles entered inside the bacterial cell by completely breaking the cell wall, leading to cell death.
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                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                03 June 2011
                June 2011
                : 16
                : 6
                : 4567-4598
                Affiliations
                Drug Transport and Delivery Research Group, Department of Pharmacy, University of Tromsø, Tromsø N-9037, Norway; Email: natasa.skalko-basnet@ 123456uit.no (N.S.-B.)
                Author notes
                [* ] Author to whom correspondence should be addressed; Email: purusotam.basnet@ 123456uit.no ; Tel.: +47-7764-6160; Fax: +47-7764-6151.
                Article
                molecules-16-04567
                10.3390/molecules16064567
                6264403
                21642934
                1b35f0ab-5d8a-4ef8-b112-bb585426cbf4
                © 2011 by the authors;

                licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 09 May 2011
                : 25 May 2011
                : 26 May 2011
                Categories
                Review

                curcumin,cancer,anti-oxidant,anti-inflammatory,nanoparticles

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