Ashwagandha and Its Active Ingredient, Withanolide A, Increase Activation of the Phosphatidylinositol 3’ Kinase/Akt Cascade in Hippocampal Neurons
Journal Title: European Journal of Medicinal Plants - Year 2017, Vol 20, Issue 2
Abstract
Aims: To determine if whether, in a hippocampal neuron culture model subjected to nutrient deprivation stress (simulating degenerative disease state), Ashwagandha and/or two of its putative active ingredients, withanolide A or withaferin A, affect any of the following: neurite outgrowth, neuronal survival, activation of the pro-survival PI-3K/Akt and MAPK cascades, phosphorylation of CREB and expression of brain-derived neurotrophic factor (BDNF). Study Design: To primary rat embryonic hippocampal neurons in culture, half of which were subjected to nutrient deprivation stress, inhibitors of the PI-3K/Akt and MAPK cascade (LY294002 and PD98059, respectively) were applied, followed by Ashwagandha, withanolide A or withaferin A. Methodology: Neuronal survival was determined by using fluorescently labeled markers for live vs dead cells and by lactate dehydrogenase assay. Average neurite length was measured under phase-contrast microscopy. And intracellular signal transduction activity was determined by Western blotting. Results: Ashwagandha increased average neurite length. Ashwagandha, withanolide A and withaferin A all increased neuron survival in nutrient deprived conditions. Ashwagandha and withanolide A increased phosphorylation of Akt, but not MAPK, in both nutrient-adequate and nutrient-deprived conditions. Withaferin A increased BDNF expression under nutrient-deprived conditions, but decreased BDNF expression under adequate nutrient conditions; withaferin A still activated Akt under both types of nutrient conditions. Conclusion: Using our model of nutrient deprivation stress, we showed that withaferin A helps cells adapt to stressful conditions, such as by increasing expression of BDNF, while withanolide A, continues to maintain cell survival and neural protection by increasing baseline levels of PI-3K/Akt. Our results are in agreement with extant literature on the effects of Ashwagandha or withaferin A on disease, such as cancer.
Authors and Affiliations
Dahae Hwang, Isabel Vasquez, Leticia Galvez, Huong Do, Anthony Lopez de Santa Ana, Shane Matta, Feimeng Zhou, Michael Chen, Amelia Russo-Neustadt
Keywords
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- EP ID EP327126
- DOI 10.9734/EJMP/2017/35355
- Views 133
- Downloads 0
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