Ashwagandha and Its Active Ingredient, Withanolide A, Increase Activation of the Phosphatidylinositol 3’ Kinase/Akt Cascade in Hippocampal Neurons | Chapter 04 | Recent Advances in Biological Research Vol. 5
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.
Author(s) Details
Michael Chen
Department of Biological Sciences, California State
University, Los Angeles, 5151 State University Dr., Los Angeles, CA 90032, USA.
Amelia Russo-Neustadt
Department of Biological Sciences, California State
University, Los Angeles, 5151 State University Dr., Los Angeles, CA 90032, USA.
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