RESUMO
Insufficient vessel maintenance adversely impacts patients in terms of tissue reperfusion following stroke or myocardial infarction, as well as during wound healing. Angiogenesis impairment is a feature typical of metabolic disorders acting at the cardiovascular level, such as diabetes. Therapeutic angiogenesis regulation offers promising clinical implications, and natural compounds as pro-angiogenic nutraceuticals hold valuable applications in regenerative medicine. By using cultured endothelial cells from human umbilical veins (HUVEC) we studied functional and molecular responses following exposure to erucin, a natural isothiocyanate derived from Brassicaceae plants and extracted from the seeds of rocket. Erucin (at nanomolar concentrations) promotes cell migration and tube formation, similar to vascular endothelial growth factor (VEGF), through mobilizing paxillin at endothelial edges. At the molecular level, erucin induces signaling pathways typical of angiogenesis activation, namely Ras, PI3K/AKT, and ERK1/2, leading to VEGF expression and triggering its autocrine production, as pharmacological inhibition of soluble VEGF and VEGFR2 dampens endothelial functions. Furthermore, erucin, alone and together with VEGF, preserves endothelial angiogenic functions under pathological conditions, such as those induced in HUVEC by high glucose (HG) exposure. Erucin emerges as a compelling candidate for therapeutic revascularization applications, showcasing promising prospects for natural compounds in regenerative medicine, particularly in addressing angiogenesis-related disorders.
Assuntos
Movimento Celular , Glucose , Células Endoteliais da Veia Umbilical Humana , Isotiocianatos , Fator A de Crescimento do Endotélio Vascular , Humanos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Isotiocianatos/farmacologia , Movimento Celular/efeitos dos fármacos , Paxilina/metabolismo , Indutores da Angiogênese/farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Brassicaceae/química , Neovascularização Fisiológica/efeitos dos fármacos , Sulfetos , TiocianatosRESUMO
: Recently the use of food by-products as natural sources of biologically active substances has been extensively investigated especially for the development of functional foods fortified with natural antioxidants. Due to their content of bioactive compounds, such as carotenoids, flavonoids and limonoids, citrus peels could be suitable to formulate enriched olive oils able to boost healthy nutrition. The aim of this study was: (i) to determine the compositional and sensory profiles of citrus olive oil; and (ii) to evaluate its nutraceutical properties in rats with high fat diet-induced metabolic syndrome and oxidative stress. The results obtained show the potential of using citrus peels as a source of bioactive compounds to improve the sensory profile as well as the phytochemical composition of olive oil. We demonstrated that the production system of Citrus x aurantium olive oil and Citrus limon olive oil improves its organoleptic properties without altering its beneficial effects, which, like control extra virgin olive oil, showed protective effects relating to glucose and serum lipid levels, metabolic activity of adipocytes, myocardial tissue functionality, oxidative stress markers and endothelial function at blood vessel level.
Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Citrus/química , Suplementos Nutricionais , Azeite de Oliva/farmacologia , Extratos Vegetais/farmacologia , Óleos de Plantas/farmacologia , Tecido Adiposo , Adulto , Animais , Antioxidantes/farmacologia , Biomarcadores , Carotenoides/farmacologia , Feminino , Flavonoides/farmacologia , Humanos , Limoninas/farmacologia , Masculino , Síndrome Metabólica , Pessoa de Meia-Idade , Azeite de Oliva/química , Estresse Oxidativo/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Ratos , Adulto JovemRESUMO
Neuropathic pain is characterized by an uncertain etiology and by a poor response to common therapies. The ineffectiveness and the frequent side effects of the drugs used to counteract neuropathic pain call for the discovery of new therapeutic strategies. Laser therapy proved to be effective for reducing pain sensitivity thus improving the quality of life. However, its application parameters and efficacy in chronic pain must be further analyzed. We investigated the pain relieving and protective effect of Photobiomodulation Therapy in a rat model of compressive mononeuropathy induced by Chronic Constriction Injury of the sciatic nerve (CCI). Laser (MLS-MiS) applications started 7 days after surgery and were performed ten times over a three week period showing a reduction in mechanical hypersensitivity and spontaneous pain that started from the first laser treatment until the end of the experiment. The ex vivo analysis highlighted the protective role of laser through the myelin sheath recovery in the sciatic nerve, inhibition of iNOS expression and enhancement of EAAT-2 levels in the spinal cord. In conclusion, this study supports laser treatment as a future therapeutic strategy in patients suffering from neuropathic pain induced by trauma.
Assuntos
Lasers , Terapia com Luz de Baixa Intensidade/métodos , Bainha de Mielina/efeitos da radiação , Neuralgia/radioterapia , Animais , Comportamento Animal , Transportador 2 de Aminoácido Excitatório/metabolismo , Hiperalgesia/complicações , Inflamação , Masculino , Proteína Básica da Mielina/metabolismo , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Limiar da Dor , Pressão , Qualidade de Vida , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/lesões , Medula Espinal/efeitos da radiaçãoRESUMO
Lymphatic leakage can be seen as a detrimental phenomenon associated with fluid retention and deposition as well as gain of weight. Moreover, lymphatic dysfunction is associated with an inflammatory environment and can be a substrate for other health conditions. A number of treatments can ameliorate lymphatic vasculature: natural substances have been used as treatment options particularly suitable for their consolidated effectiveness and safety profile. Here we report the protective effect of AdipoDren®, an association of a series of plant-derived natural complexes, on lymphatic endothelium permeability promoted by interleukin-1 beta (IL-1ß) and the associated molecular mechanisms. AdipoDren® demonstrated a protective effect on dermal lymphatic endothelial cell permeability increased by IL-1ß. Reduced permeability was due to the maintenance of tight junctions and cell-cell localisation of occludin and zonula occludens-1 (ZO-1). Moreover, AdipoDren® reduced the expression of the inflammatory key element cyclooxygenase-2 (COX-2), while not altering the levels of endothelial and inducible nitric oxide synthases (eNOS and iNOS). The upregulation of antioxidant enzymatic systems (catalase and superoxide dismutase-1, SOD-1) and the downregulation of pro-oxidant markers (p22 phox subunit of NADPH oxidase) were also evident. In conclusion, AdipoDren® would be useful to ameliorate conditions of altered lymphatic vasculature and to support the physiological functionality of the lymphatic endothelium.