RESUMEN
Moringa oleifera is widely grown throughout the tropics and increasingly used for its therapeutic and nutraceutical properties. These properties are attributed to potent antioxidant and metabolism regulators, including glucosinolates/isothiocyanates as well as flavonoids, polyphenols, and phenolic acids. Research to date largely consists of geographically limited studies that only examine material available locally. These practices make it unclear as to whether moringa samples from one area are superior to another, which would require identifying superior variants and distributing them globally. Alternatively, the finding that globally cultivated moringa material is essentially functionally equivalent means that users can easily sample material available locally. We brought together accessions of Moringa oleifera from four continents and nine countries and grew them together in a common garden. We performed a metabolomic analysis of leaf extracts (MOLE) using an LC-MSMS ZenoTOF 7600 mass spectrometry system. The antioxidant capacity of leaf samples evaluated using the Total Antioxidant Capacity assay did not show any significant difference between extracts. MOLE samples were then tested for their antioxidant activity on C2C12 myotubes challenged with an oxidative insult. Hydrogen peroxide (H2O2) was added to the myotubes after pretreatment with different extracts. H2O2 exposure caused an increase in cell death that was diminished in all samples pretreated with moringa extracts. Our results show that Moringa oleifera leaf extract is effective in reducing the damaging effect of H2O2 in C2C12 myotubes irrespective of geographical origin. These results are encouraging because they suggest that the use of moringa for its therapeutic benefits can proceed without the need for the lengthy and complex global exchange of materials between regions.
Asunto(s)
Antioxidantes , Metabolómica , Moringa oleifera , Fibras Musculares Esqueléticas , Extractos Vegetales , Hojas de la Planta , Moringa oleifera/química , Moringa oleifera/metabolismo , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/química , Metabolómica/métodos , Animales , Ratones , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/efectos de los fármacos , Línea Celular , Peróxido de Hidrógeno/metabolismo , Estrés Oxidativo/efectos de los fármacos , Metaboloma/efectos de los fármacosRESUMEN
Gender-related methodology in biomedical sciences receives considerable attention, with numerous studies highlighting biological differences between cisgender males and females. These differences influence the clinical symptoms of various diseases and impact therapeutic approaches. In this in vitro study, we investigate the potential role of sex-chromosome-related dimorphism on steroidogenic enzymes, androgen receptor (AR) expression, and cellular translocation in primary human skeletal muscle cells before and after exposure to testosterone. We analyzed 46XY and 46XX cells for 17ß-hydroxysteroid dehydrogenase (17ß-HSD), 5α-reductase (5α-R2), aromatase (Cyp-19), and AR gene expression. We also compared AR expression and intracellular translocation after increasing exposure to testosterone. At baseline, we observed higher mRNA expression for 5α-R2 and AR in 46XY cells and higher Cyp-19 mRNA expression in 46XX cells. Following testosterone exposure, we observed an increase in AR expression and translocation in 46XX cells, even at the lowest dose of 0.5 nM, while significant changes in 46XY cells were observed only from 10 nM. Our in vitro results demonstrate that the diverse sex chromosome assets reflect important differences in muscle steroidogenesis. They support the concept that chromosomal disparities between males and females, even in vitro, lead to pivotal variations in cellular physiology and response. This understanding represents a crucial starting point in gender medicine, ensuring a precise approach in clinical practice, sports, and exercise settings and facilitating the translation of in vitro data to in vivo applicability.
Asunto(s)
Receptores Androgénicos , Testosterona , Masculino , Femenino , Humanos , Testosterona/metabolismo , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Caracteres Sexuales , Andrógenos/metabolismo , Oxidorreductasas/metabolismo , Colestenona 5 alfa-Reductasa/genética , Músculo Esquelético/metabolismo , Cromosomas Sexuales/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Most anticancer treatments act on oxidative-stress pathways by producing reactive oxygen species (ROS) to kill cancer cells, commonly resulting in consequential drug-induced systemic cytotoxicity. Physical activity (PA) has arisen as an integrative cancer therapy, having positive health effects, including in redox-homeostasis. Here, we investigated the impact of an online supervised PA program on promoter-specific DNA methylation, and corresponding gene expression/activity, in 3 antioxidants- (SOD1, SOD2, and CAT) and 3 breast cancer (BC)-related genes (BRCA1, L3MBTL1 and RASSF1A) in a population-based sample of women diagnosed with primary BC, undergoing medical treatment. We further examined mechanisms involved in methylating and demethylating pathways, predicted biological pathways and interactions of exercise-modulated molecules, and the functional relevance of modulated antioxidant markers on parameters related to aerobic capacity/endurance, physical fatigue and quality of life (QoL). PA maintained levels of SOD activity in blood plasma, and at the cellular level significantly increased SOD2 mRNA (≈+77 %), contrary to their depletion due to medical treatment. This change was inversely correlated with DNA methylation in SOD2 promoter (≈-20 %). Similarly, we found a significant effect of PA only on L3MBTL1 promoter methylation (≈-25 %), which was inversely correlated with its mRNA (≈+43 %). Finally, PA increased TET1 mRNA levels (≈+15 %) and decreased expression of DNMT3B mRNA (≈-28 %). Our results suggest that PA-modulated DNA methylation affects several signalling pathways/biological activities involved in the cellular oxidative stress response, chromatin organization/regulation, antioxidant activity and DNA/protein binding. These changes may positively impact clinical outcomes and improve the response to cancer treatment in post-surgery BC patients.