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
Related Articles
- EP ID EP327126
- DOI 10.9734/EJMP/2017/35355
- Views 117
- Downloads 0
Anti-ulcer Activity of Ethanol Root Extracts of Cassia sieberiana D.C. in Albino Rats
Aims: The study was aimed at investigating the anti-ulcer activity of Cassia sieberiana fractionated root extracts using ethanol induction model in laboratory rats. Study Design: This is an experimental laboratory repor...
In vitro Modulation of Pancreatic Insulin Secretion and Extra Pancreatic Insulin Action, Enzymatic Starch Digestion and Protein Glycation by Terminalia chebula Extracts
Aim: Traditional plant treatments have been used throughout the world for the therapy of diabetes mellitus. Study Design: Using multiple in vitro models; this study was designed to investigate the efficacy and mode of a...
Acute and Sub-Acute Toxicological Evaluation of Aqueous Leaf Extract of Nauclea latifolia (Rubiaceae) in Albino Rats
Objective: Parts of Nauclea latifolia Smith (Rubiaceae) have been used extensively in ethnomedicine. Despite increasing popularity, there is paucity of information regarding its safety. We therefore evaluated the toxicol...
In vitro Shoot Multiplication of Medicinally Important Plant Andrographis lineata Nees via Nodal Explants
Andrographis lineata Nees (Acanthaceae) is an endemic herb rich in flavonoids and diterpenoids which have pharmaceutical importance. Seedling explants source has not been studied for micropropagation and hence the presen...
Toxicity of Anchomanes difformis, An Antimalarial Herb in Murine Models
Aim: Anchomanes difformis (A. difformis) is commonly used in folkloric medicine for the treatment of malaria. However, there had been no scientific evidence to substantiate this folkloric claim in murine models; hence th...