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Background: Wound healing is a complex and dynamic process that includes 3 different phases: inflammation, proliferation, and remodeling. Kinins are vasoactive peptides released after tissue injury, and are directly involved in the development and maintenance of inflammatory processes, and their actions are mediated by the activation of receptors called B1 and B2., Objective: We aimed to evaluate the involvement of kinin receptors in the skin healing process., Methods: Knockout mice for kinin receptors (KOB1, KOB2 and KOB1B2) and wild type controls (WT) were subjected to a skin excision model, and tissue repair process was evaluated during different phases of wound healing., Results: In knockout animals for kinin receptors differences were observed in the resolution period of injury exceeding 17 days for the total closure of wounds. The absence of kinin receptors promotes a significant reduction in infiltration of polymorphonuclear cells on day 2 of the inflammatory phase. Already at the late stage of this phase (3 days) there was a negative influence on the infiltration of polymorphonuclear and mononuclear cells at the site of injury in comparison to WT. Collagen was significantly diminished in tissue of KOB1, KOB2 and KOB1B2 from day two to the end of the healing process. Moreover, wound tissue from KOB2 and KOB1B2, but not KOB1, presented impaired parameters of re-epitheliazation, reduced proliferation of cells (PCNA immunostaining), and a lower number of myofibroblasts (α-SMA immunostaining)., Conclusion: These data reveal the involvement of kinin receptors in processes of skin repair. Both kinin receptors participate especially during the inflammatory phase, while B2 receptors seem to be more relevant in the quality of the wound scar. Thus, a better understanding of the contribution of kinins to skin wound healing may reveal novel options for therapy., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Ethnopharmacological Relevance: Combretum leprosum is a species that is popularly used in Brazil as a healing agent to treat skin problems and lesions. In this study we investigated the possible potential of this extract to treat inflammatory and hyperproliferative skin conditions., Materials and Methods: Classical models of skin inflammation such as TPA- and croton oil-induced mouse ear oedema were applied in order to verify the potential topical anti-inflammatory activity of the ethanolic extract from flowers of Combretum leprosum., Results: Topical application of ethanolic extract promoted a dose-dependent inhibition of phorbol ester-induced ear oedema, reduced myeloperoxidase activity and IL-6 tissue levels with inhibition comparable to dexamethasone (positive control). Histological and immunohistochemical analysis revealed that ethanolic extract also suppressed cell infiltration. Ethanolic extract altered inflammatory parameters on a chronic skin inflammation model induced by repeated applications of croton oil, decreasing ear oedema, epidermal hyperproliferation and cell infiltration. In addition, immunohistochemical analysis showed that the extract decreased PCNA expression on the epidermis., Conclusion: Taken together, these results suggest that the extract from flowers of Combretum leprosum could be considered as a new potential tool for the treatment of several skin inflammatory diseases since it reversed the skin inflammatory and hyperproliferative process in a very significant manner. Further investigations are needed in order to verify the cellular mechanism and safety of Combretum leprosum extract., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

A significant involvement of nitric oxide (NO) in the process of keratinocyte proliferation is reported with many divergences. To determine the involvement of NO in the hyperproliferative process of epidermis in vivo, non-selective inhibitor (N(G)-nitro-L-arginine-methyl ester.HCl: L-NAME) and selective inhibitors for inducible NO synthase (iNOS) and neuronal NO synthase (nNOS) (Aminoguanidine: AG and 7-Nitroindazole: 7-NI, respectively) and a NO-donor (Sodium nitroprusside: SNP) were topically applied twice a day in mice ear treated with multiple applications of croton oil. L-NAME and 7-NI treatments decreased and SNP increased ear edema formation. However, ear weight was reduced in groups that received L-NAME and 7-NI, while the AG and SNP groups presented an increment. The histological evaluation of epidermis thickness showed that all NOS inhibitors were able to prevent the increase in epidermis width caused by croton oil, while SNP contributed to enlargement. The same results were observed in the PCNA staining, where treatments with NOS inhibitors caused a reduction in the number of cells in the epidermis, while SNP caused an enhancement. 7-NI treatment reduced polymorphonuclear and mononuclear leukocytes migration when compared to the control group. The AG application increased the migration of polymorphonuclear and mononuclear cells, while the SNP enhanced only the polymorphonuclear cells. Therefore, in the skin NO produced by nNOS is involved in the control of keratinocyte hyperproliferation, with the contribution of iNOS. In the animal model of cutaneous chronic inflammation by croton oil, NO is involved in the exudation and leukocyte migration, with participation of all three enzymes., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Aim of the Study: The present work intended to study the antitumoral and antioxidant effects of Uncaria tomentosa (UT) hydroalcoholic extract in the Walker-256 cancer model., Methods and Materials: Walker-256 cells were subcutaneously inoculated in the pelvic limb of male Wistar rats. Daily gavage with UT extract (10, 50 or 100 mg kg(-1), Groups UT) or saline solution (Control, Group C) was subsequently initiated, until 14 days afterwards. For some parameters, a group of healthy rats (Baseline, Group B) was added. At the end of treatment the following parameters were evaluated: (a) tumor volume and mass; (b) plasmatic concentration of urea, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT) and lactate dehydrogenase (LDH); (c) hepatic and tumoral activity of catalase (CAT) and superoxide dismutase (SOD), as well as the rate of lipid peroxidation (LPO) and gluthatione (GSH); and (d) hepatic glutathione-S-transferase (GST) activity. The reactivity of UT extract with the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) was assessed in parallel., Results: UT hydroalcoholic extract successfully reduced the tumor growth. In addition, treatment with UT reduced the activity of AST, which had been increased as a result of tumor inoculation, thus attempting to return it to normal levels. UT did not reverse the increase of LDH and GGT plasma levels, although all doses were remarkably effective in reducing urea plasma levels. An important in vitro free radical-scavenging activity was detected at various concentrations of UT extract (1-300 microg mL(-1)). Treatment also resulted in increased CAT activity in liver, while decreasing it in tumor tissue. SOD activity was reduced in liver as well as in tumor, compared to Group C. No statistical significance concerning ALT, GST, LPO or GSH were observed., Conclusions: This data represent an in vivo demonstration of both antitumoral and antioxidant effects of UT hydroalcoholic extract. The antineoplastic activity may result, partially at least, from the ability of UT to regulate redox and metabolism homeostasis., (Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.)