Available online 17 October 2015
Highlights
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- Seabuckthorn (SBT) leaf extract improves hypoxic tolerance.
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- Cardioprotective action of SBT may be due to the upregulation of HIF-1α and its regulated proteins.
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- SBT enhances NO production and reduces endothelin-1 levels.
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- SBT ameliorates hypoxia induced ER stress.
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- SBT extracts displays anti-inflammatory and anti-apoptotic properties.
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 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.
Graphical abstract
Abbreviations
- AOPP, advanced oxidation protein products;
- CHOP, C/EBP homologous protein;
- CK-MB, creatine kinase-MB;
- DCFH-DA, 2′,7′-dichlorofluorescein-diacetate;
- eIF2, eukaryotic initiation factor 2;
- eNOS, endothelial nitric oxide synthase;
- ER, endoplasmic reticulum;
- GLUT-1, glucose transporter-1;
- GRP78, glucose regulated protein 78;
- HIF-1, hypoxia inducible factor-1α;
- HO-1, heme oxygenase-1;
- HSP, heat shock proteins;
- HSR, heat shock response;
- iNOS, inducible nitric oxide synthase;
- NF-κB, nuclear factor-κB;
- NO, nitric oxide;
- PERK, protein kinase-like ER kinase;
- ROS, reactive oxygen species;
- SBT, Seabuckthorn;
- UPR, unfolded protein response;
- VEGF, vascular endothelial growth factor
Keywords
- Oxidative stress;
- Hypoxia;
- HIF-1α;
- Nitric oxide;
- Caspase
- Corresponding author. Tel.:
+91 11 23883311; fax: +91 11 23914790.
Copyright
© 2015 Faculty of Health and Social Studies, University of South
Bohemia in Ceske Budejovice. Published by Elsevier Urban & Partner
Sp. z.o.o. All rights reserved.
