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      Calcium and potassium channels are involved in curcumin relaxant effect on tracheal smooth muscles

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          Abstract

          Context: Curcumin, the active component of Curcuma longa L. (Zingiberaceae), exhibits a wide variety of biological activities including vasodilation and anti-inflammation.

          Objective: The relaxant effect of curcumin in tracheal smooth muscle (TSM) was not examined so far, thus, this study was designed to assess the relaxant effect of curcumin on rat TSM and examine the underlying mechanism(s) responsible for this effect.

          Materials and methods: TSM was contracted by KCl (60 mM) or methacholine (10 μM), and cumulative concentrations of curcumin (12.5, 25, 50, and 100 mg/mL) or theophylline (0.2, 0.4, 0.6, and 0.8 mM, as positive control) were added to organ bath. The relaxant effect of curcumin was examined in non-incubated or incubated tissues with atropine (1 μM), chlorpheniramine (1 μM), indomethacin (1 μM), and papaverine (100 μM).

          Results: In non-incubated TSM, curcumin showed significant relaxant effects on KCl-induced contraction in a concentration-dependent manner ( p < 0.001 for all concentrations). The relaxant effects of curcumin 12.5, 25, and 50 mg/mL were significantly lower in atropine-incubated tissue compared to non-incubated TSM ( p < 0.05 to p < 0.001). A significant difference was observed in EC 50 between atropine-incubated (48.10 ± 2.55) and non-incubated (41.65 ± 1.81) tissues ( p < 0.05). Theophylline showed a significant relaxant effect on both KCl and methacholine-induced contraction in a concentration-dependent manner ( p < 0.001 for all cases).

          Conclusions: The results indicated a relatively potent relaxant effect of curcumin on TSM, which was less marked than the effect of theophylline. Calcium channel blocking and/or potassium channel opening properties of curcumin may be responsible for TSM relaxation.

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          Targeting breast stem cells with the cancer preventive compounds curcumin and piperine.

          The cancer stem cell hypothesis asserts that malignancies arise in tissue stem and/or progenitor cells through the dysregulation or acquisition of self-renewal. In order to determine whether the dietary polyphenols, curcumin, and piperine are able to modulate the self-renewal of normal and malignant breast stem cells, we examined the effects of these compounds on mammosphere formation, expression of the breast stem cell marker aldehyde dehydrogenase (ALDH), and Wnt signaling. Mammosphere formation assays were performed after curcumin, piperine, and control treatment in unsorted normal breast epithelial cells and normal stem and early progenitor cells, selected by ALDH positivity. Wnt signaling was examined using a Topflash assay. Both curcumin and piperine inhibited mammosphere formation, serial passaging, and percent of ALDH+ cells by 50% at 5 microM and completely at 10 microM concentration in normal and malignant breast cells. There was no effect on cellular differentiation. Wnt signaling was inhibited by both curcumin and piperine by 50% at 5 microM and completely at 10 microM. Curcumin and piperine separately, and in combination, inhibit breast stem cell self-renewal but do not cause toxicity to differentiated cells. These compounds could be potential cancer preventive agents. Mammosphere formation assays may be a quantifiable biomarker to assess cancer preventive agent efficacy and Wnt signaling assessment can be a mechanistic biomarker for use in human clinical trials.
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            Curcumin, a Curcuma longa constituent, acts on MAPK p38 pathway modulating COX-2 and iNOS expression in chronic experimental colitis.

            Ulcerative colitis (UC) is a nonspecific inflammatory disorder characterized by oxidative and nitrosative stress, leucocyte infiltration and up-regulation of pro-inflammatory cytokines. Mitogen-activated protein kinases (MAPKs), such as the p38 and the c-Jun N-terminal kinase (JNK) modulate the transcription of many genes involved in the inflammatory process. Curcumin is a polyphenol derived from Curcuma longa, which is known to have anti-inflammatory activity. The aim of this study was to study the effects and mechanisms of action of curcumin, on chronic colitis in rats. Inflammation response was assessed by histology and myeloperoxidase activity (MPO). We determined the production of Th1 and Th2 cytokines and nitrites in colon mucosa, as well as the expression of inducible nitric oxide synthase (iNOS), cyclo-oxygenase(COX)-1 and-2 by western blotting and inmmunohistochemistry. Finally, we studied the involvement of MAPKs signaling in the protective effect of curcumin in chronic colonic inflammation. Curcumin (50-100 mg/kg/day) were administered by oral gavage 24 h after trinitrobenzensulfonic acid (TNBS) instillation, and daily during 2 weeks before sacrifice. Curcumin significantly attenuated the damage and caused substantial reductions of the rise in MPO activity and tumour necrosis factor alpha (TNF)-alpha. Also curcumine was able to reduce nitrites colonic levels and induced down-regulation of COX-2 and iNOS expression, and a reduction in the activation of p38 MAPK; however, no changes in the activation of JNK could be observed. In conclusion, we suggest that inhibition of p38 MAPK signaling by curcumin could explain the reduced COX-2 and iNOS immunosignals and the nitrite production in colonic mucosa reducing the development of chronic experimental colitis.
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              Curcumin: A new candidate for melanoma therapy?

              Melanoma remains among the most lethal cancers and, in spite of great attempts that have been made to increase the life span of patients with metastatic disease, durable and complete remissions are rare. Plants and plant extracts have long been used to treat a variety of human conditions; however, in many cases, effective doses of herbal remedies are associated with serious adverse effects. Curcumin is a natural polyphenol that shows a variety of pharmacological activities including anti-cancer effects, and only minimal adverse effects have been reported for this phytochemical. The anti-cancer effects of curcumin are the result of its anti-angiogenic, pro-apoptotic and immunomodulatory properties. At the molecular and cellular level, curcumin can blunt epithelial-to-mesenchymal transition and affect many targets that are involved in melanoma initiation and progression (e.g., BCl2, MAPKS, p21 and some microRNAs). However, curcumin has a low oral bioavailability that may limit its maximal benefits. The emergence of tailored formulations of curcumin and new delivery systems such as nanoparticles, liposomes, micelles and phospholipid complexes has led to the enhancement of curcumin bioavailability. Although in vitro and in vivo studies have demonstrated that curcumin and its analogues can be used as novel therapeutic agents in melanoma, curcumin has not yet been tested against melanoma in clinical practice. In this review, we summarized reported anti-melanoma effects of curcumin as well as studies on new curcumin formulations and delivery systems that show increased bioavailability. Such tailored delivery systems could pave the way for enhancement of the anti-melanoma effects of curcumin.
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                Author and article information

                Journal
                Pharm Biol
                Pharm Biol
                IPHB
                iphb20
                Pharmaceutical Biology
                Taylor & Francis
                1388-0209
                1744-5116
                2020
                25 March 2020
                : 58
                : 1
                : 257-264
                Affiliations
                [a ]Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences , Mashhad, Iran;
                [b ]Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences , Bojnurd, Iran;
                [c ]Department of Physiology, School of Medicine, Mashhad University of Medical Sciences , Mashhad, Iran;
                [d ]Department of Physiology, School of Medicine, Zahedan University of Medical Sciences , Zahedan, Iran;
                [e ]Dental Materials Research Center and Department of Pediatric Dentistry, School of Dentistry, Mashhad University of Medical Sciences , Mashhad, Iran;
                [f ]Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences , Mashhad, Iran
                Author notes
                CONTACT Mohammad Hossein Boskabady boskabadymh@ 123456mums.ac.ir Neurogenic Inflammation Research Center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences , Mashhad, Iran.
                Article
                1723647
                10.1080/13880209.2020.1723647
                7170316
                32208946
                b235dc2e-f69d-4728-95ae-67136c63d895
                © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 June 2019
                : 11 January 2020
                : 26 January 2020
                Page count
                Figures: 6, Tables: 3, Pages: 8, Words: 4649
                Funding
                Funded by: Research Council of Mashhad University of Medical Sciences
                This study was financially supported by a grant from Research Council of Mashhad University of Medical Sciences.
                Categories
                Research Article

                relaxation,isometric contraction,bronchodilator agents,ion channels

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