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Biol Pharm Bull. 2019 Mar 13. doi: 10.1248/bpb.b18-00854. [Epub ahead of print]

Astragaloside IV regulates the PI3K/Akt/HO-1 signaling pathway and inhibits H9c2 cardiomyocyte injury induced by hypoxia-reoxygenation.

Author information

1
Ningbo college of health sciences.
2
The Affiliated Hospital of Medical School of Ningbo University.

Abstract

Astragaloside IV (AS-IV) is one of the main pharmacologically active compounds found in Astragalus membranaceus. AS-IV has protective effects against ischemia-reperfusion injury (IRI), but its mechanism of action has not yet been determined. This study aims to investigate the effect of AS-IV on IRI and its effect on the PI3K/Akt/HO-1 signaling pathway through in vitro experiments. Firstly, a cell culture model of myocardiocyte hypoxia-reoxygenation (H/R) injury was replicated. After AS-IV treatment, cell viability, reactive oxygen species ( ROS) levels, as well as the content or activity of the cellular factors lactate dehydrogenase(LDH), superoxide dismutase (SOD), malondialdehyde (MDA), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), were measured to evaluate the effect of treatment with AS-IV. The effect of AS-IV on HO-1 protein expression and nuclear Nrf2 and Bach1 protein expression was determined by Western blotting. Finally, a reversal of the effect of AS-IV treatment was observed following co-incubation with a PI3K inhibitor. Our results show that AS-IV has good protective effect on H/R injury and has anti-oxidative stress and anti-inflammatory effects. It can regulate the expression of Nrf2 and Bach1 proteins in the nucleus and promote the expression of HO-1 protein, while a PI3K inhibitor can partially reverse the above effects. This study suggests that the PI3K/Akt/HO-1 signaling pathway may be a key signaling pathway for the anti-IRI effect of AS-IV.

KEYWORDS:

Astragaloside IV; H9c2 cardiomyocyte; Heme oxygenase (HO-1); Phosphadylinositol 3-kinase/Akt pathway; hypoxia-reoxygenation injury

PMID:
30867343
DOI:
10.1248/bpb.b18-00854
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