Enhanced hypoxic tolerance by Seabuckthorn is due to upregulation of HIF-1? and attenuation of er stress

Abstract

An imbalance in the redox homeostasis causes activation of multifaceted signaling responses which may be protective or deleterious. Amelioration of oxidative stress is one of the major modes of action of herbal supplements like Seabuckthorn (SBT). While the antioxidant potential of SBT is known, investigations into its effect on stress inducible signaling cascades are in progress. Here, we examine the impact of SBTonhypoxic tolerance and the mechanism behind its cardioprotective action. The efficacy of SBT was evaluated using the onset of gasping time (GT) at an altitude of 9754 m as the indicator for hypoxic tolerance. SBT led to a 100% increase in GT and curtailed hypoxia induced cardiac damage and free radical production. SBT upregulated HIF-1? and ledtoatwo-fold increasein HO-1. A 100% increase in NO levels was observed. SBT reduced protein carbonylation and enhanced HSP70 levels. A statistically significant decline was seen in the markers of ER stress, GRP78, PERK and CHOP. SBT potentiated anti-inflammatory effects and downregulated NF-?B and TNF-a. Our study provides a novel insight into the mechanism behind the pro-survival effects of SBT against hypoxia, highlighting the cross talk between key adaptive responses mediated by HIF-1? and ER stress. © 2015 Faculty of Health and Social Studies, University of South Bohemia in Ceske Budejovice. Published by Elsevier Sp. z o.o. All rights reserved.