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      Marrubium vulgare L. Leave Extract: Phytochemical Composition, Antioxidant and Wound Healing Properties

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          Abstract

          Several factors contribute in wound generation, e.g., accidental traumas or surgery, and in certain cases, this dermal injury may have a devastating outcome. When skin damage occurs, the human body puts in place a sophisticated choreography, which involves numerous repairing processes to restore physiological conditions. Nevertheless, natural healing mechanisms are ineffective towards chronic or non-healing wounds and thus, therapeutic strategies may represent the only beneficial alternative to counteract these tissue insults. Over the years, numerous studies showed the great potential of plants in promoting wound healing, by virtue of their high contents in antioxidant species. These compounds trigger a molecular cascade that collimate into the promotion of reparative processes. In this article, we report on the potential effect on wound healing of Marrubium vulgare L., a medicinal plant well known for several pharmaceutical activities. To this aim, the methanolic extract was prepared and subjected to a phytochemical investigation, quantifying the amount of marrubiin via NMR and drawing the phytochemical fingerprint via high performance liquid chromatography—ultra violet/photodiode-array detection-electrospray/mass (HPLC-UV/PAD-ESI/MS) analysis. Lastly, the antioxidant properties and wound healing potential have been evaluated.

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          Wound healing: an overview of acute, fibrotic and delayed healing.

          Acute wounds normally heal in a very orderly and efficient manner characterized by four distinct, but overlapping phases: hemostasis, inflammation, proliferation and remodeling. Specific biological markers characterize healing of acute wounds. Likewise, unique biologic markers also characterize pathologic responses resulting in fibrosis and chronic non-healing ulcers. This review describes the major biological processes associated with both normal and pathologic healing. The normal healing response begins the moment the tissue is injured. As the blood components spill into the site of injury, the platelets come into contact with exposed collagen and other elements of the extracellular matrix. This contact triggers the platelets to release clotting factors as well as essential growth factors and cytokines such as platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF-beta). Following hemostasis, the neutrophils then enter the wound site and begin the critical task of phagocytosis to remove foreign materials, bacteria and damaged tissue. As part of this inflammatory phase, the macrophages appear and continue the process of phagocytosis as well as releasing more PDGF and TGF beta. Once the wound site is cleaned out, fibroblasts migrate in to begin the proliferative phase and deposit new extracellular matrix. The new collagen matrix then becomes cross-linked and organized during the final remodeling phase. In order for this efficient and highly controlled repair process to take place, there are numerous cell-signaling events that are required. In pathologic conditions such as non-healing pressure ulcers, this efficient and orderly process is lost and the ulcers are locked into a state of chronic inflammation characterized by abundant neutrophil infiltration with associated reactive oxygen species and destructive enzymes. Healing proceeds only after the inflammation is controlled. On the opposite end of the spectrum, fibrosis is characterized by excessive matrix deposition and reduced remodeling. Often fibrotic lesions are associated with increased densities of mast cells. By understanding the functional relationships of these biological processes of normal compared to abnormal wound healing, hopefully new strategies can be designed to treat the pathological conditions.
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            Wound healing: an overview of acute, fibrotic and delayed healing

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              Nitric oxide and wound repair: role of cytokines?

              Wound healing involves platelets, inflammatory cells, fibroblasts, and epithelial cells. All of these cell types are capable of producing nitric oxide (NO), either constitutively or in response to inflammatory cytokines, through the activity of nitric oxide synthases (NOSs): eNOS (NOS3; endothelial NOS) and iNOS (NOS2; inducible NOS), respectively. Indeed, pharmacological inhibition or gene deletion of these enzymes impairs wound healing. The wound healing mechanisms that are triggered by NO appear to be diverse, involving inflammation, angiogenesis, and cell proliferation. All of these processes are controlled by defined cytokine cascades; in many cases, NO appears to modulate these cytokines. In this review, we summarize the history and present state of research on the role of NO in wound healing within the framework of modulation of cytokines. Copyright 2002 Elsevier Science (USA)
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                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
                MDPI
                1420-3049
                28 October 2017
                November 2017
                : 22
                : 11
                : 1851
                Affiliations
                [1 ]Département de Biologie, Faculté des Sciences de Tunis el Manar, Unité de recherche ‘Nutrition et métabolismes azoté et protéines de stress’ (99 UR/09-20), 1002 Tunis, Tunisia; bedisamri@ 123456gmail.com (B.A.); leila.bk@ 123456planet.tn (L.B.B.-K.)
                [2 ]Department of Earth and Environmental Sciences, University of Pavia, Via S. Epifanio 14, 27100 Pavia, Italy
                [3 ]Centre for Health Technologies (CHT), University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy; silvia.rossi@ 123456unipv.it
                [4 ]Indena S.p.A., Via Don Minzoni, 6, 20090 Settala, Italy; francesca.vitulo@ 123456indena.com
                [5 ]Centro Grandi Strumenti (CGS), University of Pavia, Via Bassi 21, 27100 Pavia, Italy; federica.corana@ 123456unipv.it
                [6 ]Department of Drug Sciences, Medicinal Chemistry section, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy; marta.rui01@ 123456universitadipavia.it (M.R.); daniela.rossi@ 123456unipv.it (D.R.); michela.mori@ 123456unipv.it (M.M.)
                Author notes
                [* ]Correspondence: emanuela.martino@ 123456unipv.it (E.M.); simona.collina@ 123456unipv.it (S.C.); Tel.: +39-0382-987-379 (S.C.)
                Author information
                https://orcid.org/0000-0001-9591-4996
                https://orcid.org/0000-0003-3688-1666
                https://orcid.org/0000-0001-9511-3857
                https://orcid.org/0000-0002-2954-7558
                Article
                molecules-22-01851
                10.3390/molecules22111851
                6150401
                29143793
                f5c24ac1-fa93-4c78-bd0d-17a2f7d238f7
                © 2017 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 (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 06 September 2017
                : 26 October 2017
                Categories
                Article

                wound healing,marrubium vulgare l. leave extract,q-nmr,antioxidant properties,hplc-uv/pad ms analysis

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