RESUMEN
Proanthocyanidins are phenolic compounds abundant in the diet, commonly found in grapes and derivatives, foods known for their health-promoting benefits. There is previous evidence showing the antidiabetic activity of proanthocyanidins, however, their mechanisms of action have not been fully elucidated. This study evaluated the capacity of grape seed proanthocyanidins extract (GSPE) to modulate oxidative stress, nitric oxide levels, mitochondrial dysfunction, apoptosis, and sirtuin expression in endothelial cells EA.hy926 under high glucose condition. In addition, the possible toxic effects of GSPE was evaluated in a zebrafish embryos model. The results showed that GSPE was able to enhance cell viability and avoid the disturbance in redox metabolism induced by high glucose. Moreover, GSPE was able to avoid mitochondria dysfunction and the increased in p53 and poly-(ADP-ribose) polymerase expression induced by high glucose exposition. These effects were attributed to the increase in expression of sirtuin 3, a protein able to regulate mitochondrial function. GSPE in an effective concentration did not show toxic effects in zebrafish embryos model. Taken together, these data elucidate the key molecular target of GSPE for future pharmacological interventions in diabetic patients.
Asunto(s)
Extracto de Semillas de Uva/farmacología , Estrés Oxidativo/efectos de los fármacos , Proantocianidinas/farmacología , Sirtuina 3/metabolismo , Animales , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Células Endoteliales/metabolismo , Glucosa/metabolismo , Extracto de Semillas de Uva/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Modelos Animales , Óxido Nítrico/metabolismo , Proantocianidinas/metabolismo , Vitis/metabolismo , Pez CebraRESUMEN
Grape proanthocyanidins are compounds widely ingested in the diet. This study evaluated their effects on mitochondrial function, apoptosis, and sirtuin 1 and 3 expressions in HEK-293 cells exposed to H2 O2 . High-resolution mass spectrometry and high-performance liquid chromatography characterized the proanthocyanidins extract and the presence of procyanidins B and C was detected. The extract prevented H2 O2 -induced oxidative damage to proteins and lipids and depletion in superoxide dismutase activity. Moreover, it was able to regulate the expression of NADH: Ubiquinone oxidoreductase core subunit S7 and prevent mitochondrial electron transport chain dysfunction, ATP depletion, and apoptosis induced by H2 O2 . Finally, the extract was able to regulate sirtuin 1 and 3 expressions, thus maintaining cell viability. These data show that the grape seed proanthocyanidins can target mitochondrial proteins, which may represent an important approach for the management of numerous chronic illnesses associated with mitochondrial dysfunction. PRACTICAL APPLICATIONS: Proanthocyanidins are phenolic compounds abundant in regular diet, commonly found in grapes and derivatives, pomegranates, apples, and red fruits, all foods known for their beneficial effects on health. The current study highlights the role of proanthocyanidins as mitochondrial modulators that may explain the biological activity attributed to these compounds. This study brings evidence that proanthocyanidins might be considered as a value-added agent for the development of new nutraceutical and or pharmaceutical approaches.
Asunto(s)
Extracto de Semillas de Uva , Proantocianidinas , Apoptosis , Extracto de Semillas de Uva/farmacología , Células HEK293 , Humanos , Riñón , Mitocondrias , Proantocianidinas/farmacología , Sirtuina 1RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Ethnopharmacological knowledge is important for the identification of active compounds from natural products. Pain may have different aetiologies with complex mechanisms. Tabernaemontana catharinensis A. DC. is well known for indole alkaloids, being used empirically in folk medicine, with antimicrobial and anti-inflammatory as well as antiofidic actions among others. AIM OF THE STUDY: This work aims to evaluate the antinociceptive and antioxidant effect in mice of the alkaloids extract from leaves of Tabernaemontana catharinensis A. DC. (AITc). MATERIALS AND METHODS: The AITc was produced by ultrasound and acid-base extraction, and the chemical composition was evaluated by high resolution mass spectrometry. Male mice (Mus musculus), Swiss, were used for in vivo tests. The AITc was administrated at doses of 1.0, 5.0, and 10.0â¯mg/kg in acetic acid model, formalin, tail-immersion, hot plate, and open field tests, and compared to saline, morphine, or diazepam controls, depending on the test. The toxicological, biochemical, haemogram and antioxidant effect were evaluated in mouse organs such as liver, brain, kidneys, spleen and stomach. RESULTS: In total, 10 compounds were identified in the AITc, being from the indole alkaloids from the ibogan and corynanthean classes. The extract in doses ranging from 5.0 to 10.0â¯mg/kg showed an antinociceptive effect for acetic acid, inhibiting by 47.7% and 61.6%. In the same line, reductions of 47.1% (first phase) and 43.6% (second phase) were observed for the 5.0â¯mg/kg dose in the formalin test. However, tail-immersion and hot plate tests did not show considerable modifications in the latency period, while in the open field test there was an inhibition of only 5.1%. It was observed no differences in NO levels and total antioxidant status of the mice in any of the studie tissues. CONCLUSIONS: The results justify the use of this plant in traditional medicine. in vivo tests indicate that these compounds possess central and peripheral mechanisms of action. This is study that reports the nociceptive action of these alkaloids, also including toxicity tests, which are intended to guarantee the safety of use of extracts of this plant.