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Harpagide from Scrophularia protects rat cortical neurons from oxygen-glucose deprivation and reoxygenation-induced injury by decreasing endoplasmic reticulum stress.

Abstract：

ETHNOPHARMACOLOGICAL RELEVANCE:Harpagide is the main ingredient in Scrophularia ningpoensis Hemsl which is used for the therapeutic purpose of treating encephalopathy. Harpagide has shown promise in the treatment of oxygen-glucose deprivation and reoxygenation (OGD/R)-induced brain injury. However, the underlying mechanisms remain unclear. AIM OF STUDY:In this study, we aimed to determine the neuroprotective effect of harpagide on rat cortical neurons under OGD/R conditions that induce the development of ischaemia-reperfusion (I/R). MATERIALS AND METHODS:To explore the biological function of harpagide in cerebral ischaemia-reperfusion injury (CIRI), The CIRI model was established by oxygen-glucose deprivation and reoxygenation (OGD/R) on rat cortical neurons. It tested cell survival rate by 3-(4,5-dimethylthiazol-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, apoptosis by flow cytometry, intracellular Ca2+ concentration [Ca2+] i by cofocal laser, and expressions related to endoplasmic reticulum stress (ERS) by RT-PCR and Western blot. RESULTS:We found that pretreatment with harpagide (50 μM) prevented OGD/R-induced apoptotic cell death. Harpagide also significantly decreased the gene expression levels and protein production of ERS-related proteins. We found that harpagide also exerted a neuroprotective effect on TG-induced apoptosis in rat cortical neurons and decreased the gene expression levels and protein production of GRP78, caspase-12 and CHOP. We also measured the intracellular calcium ion concentration ([Ca2+]i) in neurons and found that harpagide significantly decreased the [Ca2+]i induced by OGD/R and TG. CONCLUSION:These results suggest that harpagide protects against OGD/R-induced cell apoptosis, likely by decreasing ERS. Collectively, harpagide was demonstrated to be a prominent suppressor of ERS and prevented the apoptosis of rat cortical neurons. Based on the results, harpagide could potentially serve as a therapeutic agent of ischaemia-like injury associated with excessive ERS and apoptosis.

journal_name

J Ethnopharmacol

journal_title

Journal of ethnopharmacology

authors

Wang K,Lou Y,Xu H,Zhong X,Huang Z

doi

10.1016/j.jep.2020.112614

subject

Has Abstract

pub_date

2020-05-10 00:00:00

pages

112614

eissn

0378-8741

issn

1872-7573

pii

S0378-8741(19)32822-3

journal_volume

253

pub_type

杂志文章

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Harpagide from Scrophularia protects rat cortical neurons from oxygen-glucose deprivation and reoxygenation-induced injury by decreasing endoplasmic reticulum stress.