Abstract In this study, the synergistic effects of jujube polysaccharide (JP) and flavonoid (JF) on aging mice were investigated. Sub-acutely aging mouse models were established using D-galactose. Eighty experimental mice were randomly assigned to normal, model, vitamin C (200 mg/kg), JP (200 mg/kg), JF (200 mg/kg) and JP + JF (low (100 mg/kg), medium (200 mg/kg), and high-dose (300 mg/kg)) groups (10 mice in per group). After 35 days, the physiological aging indices of mice were measured. JP and JF displayed significantly positive synergistic antiaging effects. Compared with an aging model control group, groups administered JP and JF showed increased indices for the thymus and spleen and significantly increased activities of SOD and GSH-PX in the heart, liver, spleen, and brain (R2 > 0.99, P < 0.01; R2 > 0.98, P < 0.01). The contents of MDA in heart, liver, spleen, brain and serum were significantly decreased (R2 > 0.95, P < 0.01), while those of HYP in skin and serum were significantly increased. The concentrations of neurotransmitters (NE, DA, 5-HT, 5-HIAA) in the brain and serum of mice were significantly increased (P < 0.01). These results indicated that JP and JF acted not only on relevant tissues or organs of mice, but on all body systems.

Abstract To determine the synergistic anti-inflammatory effects of resveratrol (RES) combined with vitamin E (VE) and its mechanism. Lipopolysaccharide (LPS)-induced RAW264.7 cells were used to determine the effect of resveratrol, vitamin E and their combination on the production of cellular inflammatory mediators, including NO, IL-6, TNF-α, IL-1β, TLR4 and p-NF-κBp65. The synergistic anti-inflammatory effect of the combination was evaluated by ELISA, and the effect of the combination on the TLR4, p-NF-κBp65 and p-IĸBα pathway by Western blot. The results showed that resveratrol combined with vitamin E synergistically inhibited the production of NO, LDH, MPO and inflammatory factors IL-6, TNF-α, IL-1β and TLR4 by LPS-stimulated macrophages, and effectively inhibited the expression of TLR4, p-NF-κBp65 (P<0.01). Resveratrol combined with vitamin E have a synergistic anti-inflammatory effect. They can inhibit the expression of inflammatory mediators and further suppress the activation of TLR4, p-NF-κBp65 and p-IĸBα signaling pathway in LPS-induced RAW264.7 cell, which might provide a new effective way for inflammation treatment.

Resumo Fundamento: É sabido que a resistência à insulina e a hiperglicemia são causas patológicas importantes no desenvolvimento de cardiomiopatia diabética (CMD). Entretanto, seus mecanismos moleculares precisos na patogênese da CMD ainda não estão claros. Objetivos: Estudos recentes revelam que os microRNAs (miRNAs) desempenham papéis essenciais na patogênese da CMD. Este projeto tem o objetivo de determinar os papéis de miR-34a e miR-125b na morte celular de cardiomiócitos causada por hiperglicemia. Métodos: Cardiomiócitos primários de ratos foram isolados e expostos a concentrações de glicose normais e altas. A viabilidade das células foi medida utilizando-se o ensaio MTT. As expressões de miR-34a e miR-125b foram detectadas por qRT-PCR. Alvos potenciais de miR-34a e miR-125b foram previstos pelo www.Targetscan.org, e validados a partir de tecidos cardíacos humanos. Um p<0,05 foi considerado significância estatística. Resultados: Demonstra-se neste estudo que o miR-34a e o miR-125b têm resposta celular reduzida no coração humano diabético. Além disso, os dados in vitro de cardiomiócitos primários de ratos demonstraram que o tratamento com glicose alta em curto prazo estimula a expressão de miR-34a e miR-125b. Demonstrou-se que, em condições de glicose alta, os cardiomiócitos de ratos apresentaram metabolismo de glicose intracelular, e a captação de glicose e a produção de lactato aumentaram significativamente. Foi identificado que as principais enzimas metabólicas da glicose, hexoquinase 2 (HK2) e lactato desidrogenase-A (LDHA) eram alvos diretos de miR-125b e miR-34a, respectivamente. A superexpressão de miR-125b e miR-34a poderia evitar a morte de celular de cardiomiócitos causada por hiperglicemia. Por fim, a recuperação de HK2 e LDHA em cardiomiócitos com superexpressão de miR-125b e miR-34a restaurou a sensibilidade de cardiomiócitos à hiperglicemia. Conclusões: Nossos resultados propõem um mecanismo molecular para proteção cardiovascular diabética mediada por microRNA e contribuirão para o desenvolvimento de estratégias de tratamento de disfunção cardiovascular associada a diabetes.

Abstract Background: It is well-known that insulin resistance and hyperglycemia are important pathological causes for the development of diabetic cardiomyopathy (DCM). However, its precise molecular mechanisms in the pathogenesis of DCM remain unclear. Objectives: Recent studies reveal that microRNAs (miRNA) play essential roles in the pathogenesis of DCM. This project aimed to determine the roles of miR-34a and miR-125b in hyperglycemia-induced cardiomyocyte cell death. Methods: Rat primary cardiomyocytes were isolated and exposed to normal and high concentrations of glucose. Cell viability was measured using MTT assay. Expressions of miR-34a and miR-125b were detected by qRT-PCR. Potential targets of miR-34a and miR-125b were predicted from www.Targetscan.org and validated from human heart tissues. A statistical significance of p<0.05 was considered. Results: The present study shows that miR-34a and miR-125b are downregulated in a human diabetic heart. Moreover, in vitro data from rat primary cardiomyocytes showed that short-term high glucose treatment stimulates miR-34a and miR-125b expressions. Under high glucose, it was found that rat cardiomyocytes displayed increased intracellular glucose metabolism, and glucose uptake and lactate production were significantly increased. It was also found that the key glucose metabolic enzymes, Hexokinase 2 (HK2) and Lactate dehydrogenase-A (LDHA), were direct targets of miR-125b and miR-34a, respectively. Overexpression of miR-125b and miR-34a could prevent hyperglycemia-induced cardiomyocyte cell death. Finally, the restoration of HK2 and LDHA in miR-125b and miR-34a overexpressed cardiomyocytes recovered the cardiomyocytes’ sensitivity to hyperglycemia. Conclusion: Our results proposed a molecular mechanism for the microRNA-mediated diabetic cardiovascular protection and will contribute to developing treatment strategies for diabetes-associated cardiovascular dysfunction.