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Upregulation of heme oxygenase-1 and activation of Nrf2 by the phytochemicals in protandim




Reuland, Danielle Judith, author
Hamilton, Karyn L., advisor
Miller, Benjamin F., committee member
Frye, Melinda A., committee member

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Increased production of reactive oxygen species has been implicated in the pathogenesis of cardiovascular disease (CVD), with enhanced endogenous antioxidants proposed as a potential mechanism for promoting redox balance. Protandim is a well-defined combination of five widely studied medicinal plants derived from botanical sources [Bacopa monniera, Silybum marianum (milk thistle), Withania somnifera (Ashwagandha), Camellia sinensis (green tea), and Curcuma longa (turmeric)]. The purpose of this study was to determine if treatment of cardiomyocytes with Protandim induces phase II detoxification enzymes, including the endogenous antioxidant heme oxygenase-1 (HO-1), with activation of nuclear factor E2 p45-related factor 2 (Nrf2), and protection from oxidative stress induced apoptosis. In cultured cardiomyocytes, treatment with Protandim was associated with activation of Nrf2 and a significant increase in HO-1. Protandim supplemented cells were protected against hydrogen peroxide-induced apoptosis as assessed by TUNEL (35% apoptotic in untreated vs. 5% apoptotic in Protandim treated). These findings support the use of Protandim as a potential method for upregulation of antioxidant defenses and protection of heart cells against an oxidative challenge. Future studies will focus on optimizing phytochemical induction of Nrf2-mediated antioxidant defenses in relevant in vivo models of CVD.


Department Head: Richard Gay Israel.

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