From Inflammation to Current and Alternative Therapies Involved in Wound Healing

Wound healing is a complex event that develops in three overlapping phases: inflammatory, proliferative, and remodeling. These phases are distinct in function and histological characteristics. However, they depend on the interaction of cytokines, growth factors, chemokines, and chemical mediators from cells to perform regulatory events. In this article, we will review the pathway in the skin healing cascade, relating the major chemical inflammatory mediators, cellular and molecular, as well as demonstrating the local and systemic factors that interfere in healing and disorders associated with tissue repair deficiency. Finally, we will discuss the current therapeutic interventions in the wounds treatment, and the alternative therapies used as promising results in the development of new products with healing potential

Modulation of metabolic and inflammatory parameters by hydroalcoholic extract of Musa cavendish green peels in nonalcoholic fatty liver disease

Musa cavendish, comumente conhecido como banana, é uma fruta com estudos científicos limitados sobre as atividades biológicas das suas cascas. Assim, decidimos investigar a composição química e os efeitos do extrato hidroalcoólico das cascas verdes do fruto de Musa cavendish (EHB) como modelo de tratamento preventivo e farmacológico da doença do fígado gorduroso não alcoólico (NAFLD, do inglês) induzida por dieta hiperlipídica em camundongos. A composição química do EHB foi determinada por HPLC-UV/Vis e FIA-ESI-IT-MSn. Foram identificados 12 compostos de diferentes classes, incluindo derivados de ácidos fenólicos, flavonóides agliconas, flavonóides glicosídicos e catecolaminas. O efeito da administração preventiva e farmacológica do EHB sobre a NAFLD foi avaliado pela determinação da composição corporal, instalação de resistência insulínica periférica, além do monitoramento do perfil glicêmico, lipídico, hepático e hormonal plasmáticos. O comprometimento hepático foi avaliado por histologia, expressão gênica e conteúdo proteico de reguladores metabólicos e inflamatórios, assim como marcadores antioxidantes. Os animais tratados com o EHB apresentaram redução do peso corporal, dos tecidos adiposos e do Índice de Lee. O EHB diminuiu os níveis séricos de glicose, triglicerídeos, colesterol total, colesterol-LDL, ácidos graxos livres, aspartato aminotransferase (AST), insulina, leptina, peptídeo inibitório gástrico (GIP) total e resistina e aumentou os níveis séricos de colesterol-HDL. O tratamento modulou a expressão gênica de diversas enzimas envolvidas no metabolismo lipídico, como glicerol-3-fosfato aciltransferase-4 (GPAT4), diacilglicerol O-aciltransferase 2 (DGAT2), HMG-CoA redutase, acil-CoA oxidase (ACOX) e colesterol 7 alfa-hidroxilase (CYP7A1) no tecido hepático. Além disso, o tratamento preventivo com EHB aumentou o peso e o conteúdo de glicogênio no fígado. A análise histológica mostrou que o EHB reduziu a esteatose, a balonização e a inflamação lobular. A redução da inflamação foi confirmada pelo menor conteúdo de TNF-alfa, IL-6, MIP-2, IL-1beta e NF-capaB p65 nuclear e aumento de IL-10 e da atividade da enzima superóxido dismutase (SOD). Assim, nossos resultados indicam o potencial do EHB como agente protetor e terapêutico nos camundongos obesos com a doença do fígado gorduroso não alcoólico induzida por dieta hiperlipídica, modulando os parâmetros metabólicos e inflamatóriosMusa cavendish, commonly known as banana, is a fruit with limited scientific studies regarding the biological activities of its peels. Thus, we decided to investigate the chemical composition and effects of hydroalcoholic extract of Musa cavendish fruit green peels (EHB) as a model of preventive and pharmacological treatment of high fat dietinduced nonalcoholic fatty liver disease (NAFLD) in mice. The chemical composition of EHB was determined by HPLC-UV/Vis and FIA-ESI-IT-MSn. Twelve compounds of different classes were identified, including derivatives of phenolic acids, aglycone flavonoids, glycosidic flavonoids and catecholamines. The effect of preventive and pharmacological administration of EHB on NAFLD was assessed by determination of body composition, peripheral insulin resistance, and plasma glycemic, lipid, hepatic and hormonal profiles. Hepatic impairment was evaluated by histology, gene expression and protein content of metabolic and inflammatory regulators, as well as antioxidant markers. The animals treated with EHB showed reduction in body weight, adipose tissue and Lee Index. EHB decreased serum glucose, triglyceride, total cholesterol, LDL-cholesterol, free fatty acid, aspartate aminotransferase (AST), insulin, leptin, total gastric inhibitory peptide (GIP) and resistin levels and increased serum HDL-cholesterol levels. Treatment modulated gene expression of several enzymes involved in lipid metabolism, such as glycerol-3-phosphate acyltransferase-4 (GPAT4), diacylglycerol O-acyltransferase 2 (DGAT2), HMG-CoA reductase, acyl-CoA oxidase (ACOX) and cholesterol 7Alpha- hydroxylase (CYP7A1) in liver tissue. In addition, preventive EHB treatment increased liver weight and glycogen content. Histological analysis showed that EHB reduced steatosis, ballooning and lobular inflammation. Inflammation reduction was confirmed by lower content of TNF-Alpha, IL-6, MIP-2, IL-1Beta and nuclear NF-CapaB p65 and increased IL- 10 and superoxide dismutase (SOD) activity. Thus, our results indicate the potential of EHB as a protective and therapeutic agent in obese mice with non-alcoholic fatty liver disease induced by hyperlipidic diet, modulating metabolic and inflammatory parameter

PGC-1 alpha in regulating inflammatory in nonalcoholic steatohepatitis

A doença hepática gordurosa não-alcoólica (NAFLD, do inglês) é a manifestação clínica hepática da síndrome metabólica, cuja incidência aumenta consideravelmente em todo o mundo. A NAFLD pode progredir para um estado de esteatohepatite não-alcoólica (NASH, do inglês), caracterizado por inflamação hepatocelular, com ou sem fibrose. Dados na literatura mostram que o coativador-1 alfa do receptor ativado por proliferadores de peroxissoma gama (PGC-1alfa), além de estar envolvido em diversos processos metabólicos, representa uma estratégia terapêutica promissora na modulação da inflamação. Neste projeto investigamos as alterações inflamatórias no fígado induzida por dieta hiperlipídica e o papel do PGC-1alfa nesse processo. Camundongos C57black/6 receberam dieta hiperlipídica contendo 30% de gordura por 10 semanas. O peso dos animais foi avaliado semanalmente. Após a eutanásia, o tecido adiposo intra-abdominal (retroperitoneal e periepididimal) foi coletado e pesado. Analisamos o perfil glicêmico e lipídico sérico e expressão de genes envolvidos no metabolismo glicêmico e lipídico. Avaliou-se também o aspecto histológico e a inflamação do tecido hepático por quantificação das citocinas IL-6, TNF-alfa e IL-1beta. A dieta rica em gordura conduziu a um aumento dos depósitos de gordura intra-abdominal, hiperglicemia e hiperlipidemia. Os animais também apresentavam esteatohepatite, com aumento de citocinas pró-inflamatórias e diminuição na expressão de PGC-1alfa no tecido hepático. O envolvimento do PGC-1alfa na produção de mediadores inflamatórios por hepatócitos foi avaliado em células HepG2 utilizando RNA de interferência (RNAi). O knockdown da expressão de PGC-1alfa causou aumento na expressão e liberação de IL-6 em hepatócitos via aumento na fosforilação de IkBalfa e consequente ativação do NFkB. Portanto, nossos dados mostram que o PGC-1alfa inibe a produção de mediadores inflamatórios (IL-6) em hepatócitos, e fornecem novas evidências das conexões existentes entre as vias metabólicas e imunesNonalcoholic fatty liver disease (NAFLD) is the liver clinical manifestation of the metabolic syndrome, whose incidence increases considerably around the world. NAFLD may progress to a state of non-alcoholic steatohepatitis, characterized by hepatocellular inflammation, with or without fibrosis. Data in the literature show that the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1alfa), a protein involved in various metabolic processes, represents a promising therapeutic strategy in the modulation of inflammation. In this project, we investigate the inflammatory changes in the liver induced by high fat diet and the role of PGC-1alfa in this process. C57black/6 mice were fed a high fat diet containing 30% fat for 10 weeks. The weight of the animals was measured weekly. After euthanasia, the intra-abdominal adipose tissue (retroperitoneal and periepididymal) was collected and weighed. We have analyzed the glycemic and serum lipid profile and expression of genes involved in glucose and lipid metabolism. We also assessed liver morphology by HE staining and inflammation by quantification of the cytokines IL-6, TNF-alfa and IL-1beta. The high fat diet led to an increase in intra-abdominal fat deposits, hyperglycemia and hyperlipidemia. Animals also presented steatohepatitis, an increased proinflammatory cytokines and decreased PGC-1alfa expression in the hepatic tissue. The involvement of PGC-1alfa on inflammatory mediators production by hepatocytes was evaluated in HepG2 cells using RNA interference (RNAi). The knockdown of PGC-1alfa expression caused an increase in IL6 expression and release by hepatocytes via the increase in the IkBalfa phosphorylation and subsequent activation of NFkB. Therefore, our data show that PGC-1alfa inhibits the production of inflammatory mediators (IL-6) in hepatocytes and provide further evidence of the connections between the metabolic and immune pathway

From Inflammation to Current and Alternative Therapies Involved in Wound Healing

Wound healing is a complex event that develops in three overlapping phases: inflammatory, proliferative, and remodeling. These phases are distinct in function and histological characteristics. However, they depend on the interaction of cytokines, growth factors, chemokines, and chemical mediators from cells to perform regulatory events. In this article, we will review the pathway in the skin healing cascade, relating the major chemical inflammatory mediators, cellular and molecular, as well as demonstrating the local and systemic factors that interfere in healing and disorders associated with tissue repair deficiency. Finally, we will discuss the current therapeutic interventions in the wounds treatment, and the alternative therapies used as promising results in the development of new products with healing potential