J Appl Biomed 14:71-83, 2016 | DOI: 10.1016/j.jab.2015.10.001

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

Kanika Jain, Geetha Suryakumar^*, Rajendra Prasad, Lilly Ganju, Shashi Bala Singh

Cellular Biochemistry Division, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi 110 054, India

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 SBT on hypoxic 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-1α and led to a two-fold increase in 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-κB and TNF-α. 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-1α and ER stress.

Keywords: Oxidative stress; Hypoxia; HIF-1α; Nitric oxide; Caspase

Received: May 20, 2015; Revised: October 2, 2015; Accepted: October 5, 2015; Published: February 1, 2016  Show citation