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[This corrects the article DOI: 10.1155/2018/5386079.].
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BACKGROUND: Flavonoids have been characterized as a prominent class of compounds to treat thrombotic diseases through the inhibition of thiol isomerases. Syzygium cumini is a flavonoid-rich medicinal plant that contains myricetin and gallic acid. Little is known about the potential antiplatelet properties of S. cumini and its constituent flavonoids. OBJECTIVE: To evaluate the antiplatelet effects and mechanism of action of a polyphenol-rich extract (PESc) from S. cumini leaf and its most prevalent polyphenols, myricetin and gallic acid. METHODS: PESc, myricetin, and gallic acid were incubated with platelet-rich plasma and washed platelets to assess platelet aggregation and activation. In vitro platelet adhesion and thrombus formation as well as in vivo bleeding time were performed. Finally, myricetin was incubated with recombinant thiol isomerases to assess its potential to bind and inhibit these, while molecular docking studies predicted possible binding sites. RESULTS: PESc decreased platelet activation and aggregation induced by different agonists. Myricetin exerted potent antiplatelet effects, whereas gallic acid did not. Myricetin reduced the ability of platelets to spread on collagen, form thrombi in vitro without affecting hemostasis in vivo. Fluorescence quenching studies suggested myricetin binds to different thiol isomerases with similar affinity, despite inhibiting only protein disulfide isomerase (PDI) and ERp5 reductase activities. Finally, molecular docking studies suggested myricetin formed non-covalent bonds with PDI and ERp5. CONCLUSIONS: PESc and its most abundant flavonoid myricetin strongly inhibit platelet function. Additionally, myricetin is a novel inhibitor of ERp5 and PDI, unveiling a new therapeutic perspective for the treatment of thrombotic disorders.
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Syzygium cumini (L.) Skeels has been reported to exert anti-inflammatory and cardiometabolic activities due to its high content of polyphenols. We characterized the chemical composition and assessed the antidiabetic effects of a novel polyphenol-rich extract (PESc) obtained from S. cumini leaf. Rats were injected with alloxan (150 mg/kg, ip, ALX group) and followed up for 7 days. Some were orally treated with PESc (50 mg/kg/day) for 7 days before and after diabetes induction (ALX-PP) or only for 7 days after alloxan injection (ALX-P). ALX-P and ALX-PP decreased fasting glycemia in 37 and 43%, respectively, as compared to ALX. Triglycerides and total cholesterol serum levels were also significantly reduced in comparison to ALX. PESc presented high polyphenol concentration (71.78 ± 8.57 GAE/100 g), with flavonoid content of 8.21 ± 0.42 QE/100 g. Upon HPLC-MS/MS and MS/MS studies, five main polyphenols-gallic acid, quercetin, myricetin, and its derivatives-were identified. Myricetin was predominant (192.70 ± 16.50 µg/mg PESc), followed by measurable amounts of gallic acid (11.15 ± 0.90 µg/mg PESc) and quercetin (4.72 ± 0.06 µg/mg PESc). Kinetic assessment of total antioxidant capacity revealed PESc high potency, since maximum response was reached within 5 min reaction time in a concentration-dependent manner. Specific antioxidant activity of PESc was assessed against both DPPH⢠and ABTSâ¢+, showing strong activity (IC50: 3.88 ± 1.09 and 5.98 ± 1.19 µg/mL, resp.). PESc also inhibited lipoxygenase activity (IC50: 27.63 ± 8.47), confirming its antioxidant activity also on biologically relevant radicals. Finally, PESc induced insulin secretion by directly stimulating INS-1E ß cells in the absence of any cytotoxic effect. Overall, our results support that PESc is a potent antioxidant phytocomplex with potential pharmacological use as a preventive antidiabetic natural product.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Polifenóis/química , Syzygium/química , Animais , Antioxidantes/metabolismo , Glicemia/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus Experimental/metabolismo , Insulina/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Espectrometria de Massas em Tandem , Triglicerídeos/sangueRESUMO
Fundamento: A prevalência de hipertensão arterial (HA) tem apresentado valores significantes na adolescência, principalmente quando associada a outros fatores de risco cardiovasculares. Objetivos: O presente trabalho objetivou realizar um estudo preventivo e epidemiológico de HA associada a fatores de risco, como dislipidemias, diabetes e obesidade, em escolares da rede pública, com faixa etária de 14 a 17 anos, no Colégio Estadual DomPedroII, em Umuarama Paraná. Material e métodos:Foram avaliados 150 adolescentes, submetidos a dosagens bioquímicas de colesterol total (CT), triglicerídeos (TGC), glicose e exames físicos, como pressão arterial (PA) e índice de massa corpórea (IMC). Resultados:Osresultados das análisesdemonstraram uma prevalência de HA neste grupo estudado de 6,7%. Dos indivíduos com IMC elevado, 4 apresentaram associada a PA alterada, representando 21,1%. Em relação ao perfil lipídico alterado, 3 (18,8%) apresentaram CT e PA alterados, e 4 (17,4%) demonstraram TGC e PA elevados. Dos indivíduos com hiperglicemia, 2 (66,7%) também apresentaram PA alterada. Conclusão:Concluiu-se que é de extrema importância e necessidade a criação de medidas preventivas e profiláticas, proporcionando uma vida mais saudável, a fim de evitar que adolescentes da atualidade se tornem adultos hipertensos
Background: The prevalence of hypertension blood has made significant values in adolescence, especially when associated with other cardiovascular risk factors. Objective: The present study aimed to perform an epidemiological prevention study of hypertension blood associated with risk factors, such as dyslipidemia, diabetes and obesity, among public school pupils, aged from 14 to 17 years in Colégio Estadual Dom Pedro II, in Umuarama Paraná. Materials and methods:Weevaluated 150adolescents who underwent biochemical levels of total cholesterol (TC), triglycerides (TGC), glucose and physical examinations, such as blood pressure (PA) andbody mass index (BMI). Results: The results showed a prevalence of hypertension blood in this study group of 6.7%. Of those individuals with high BMI, 4 were associated with elevated blood pressure, representing 21.1%. In relation to the altered lipid profile, 3 (18.8%) had altered blood pressure and TC, and 4 (17.4%) showed elevated GCT and blood pressure. Among individuals with hyperglycemia, 2 (66.7%) also had abnormal blood pressure. Conclusion:Itwas concluded that it is extremely important and necessary to develop preventive and prophylactic measures, in orderto prevent teenagers becoming, hypertensive adults, providing a healthier life.