A novel biscoumarin derivative dephosphorylates ERK and alleviates apoptosis induced by mitochondrial oxidative damage in ischemic stroke mice.

Abstract

AIM:

We previously reported the protective effects of biscoumarin derivatives against oxidative stress, but effects of the derivative on mitochondrial oxidative damage induced apoptosis in ischemic stroke remains unknown.

METHODS:

Primary neurons were subjected to oxygen and glucose deprivation (OGD) for the in vitro simulation of ischemic stroke, and an ischemic stroke model was established in mice by operation of middle cerebral artery occlusion (MCAO).

RESULTS:

The results indicated that the nontoxic concentration range of biscoumarin derivative Comp. B in neurons was from 0 to 30 μg/ml and the optimal protective concentration was 20 μg/ml. Treatment with Comp. B increased the cell survival rate and alleviated mitochondrial oxidative damage and apoptosis in OGD-treated neurons. Comp. B reduced the ratio of Bax/Bcl-2, inhibited the phosphorylation of ERK, and thus alleviated apoptosis in OGD-treated neurons. Further research demonstrated that the dephosphorylation effect on ERK of Comp. B is a key factor in alleviating apoptosis in neurons induced by OGD injury. Furthermore, Comp. B reduced the infarct volume, improved neurobehavioural score, and alleviated morphological changes and brain apoptosis in MCAO mice.

CONCLUSION:

The novel biscoumarin derivative Comp. B alleviates mitochondrial oxidative damage and apoptosis in ischemic stroke mice. These findings might provide new insights that will aid in elucidating the effect of biscoumarin derivative against cerebral ischemic reperfusion injury and support the new development of Comp. B as a potential treatment for ischemic stroke.

• Authors: Jun Wang, Wentong Zhang, Bo Ma, Hongchen Zhang, Zhaoyang Fan, Mingkai Li, Xia Li
• Journal: Life sciences (Life Sci) Vol. 264 Pg. 118499 (Jan 01 2021) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 33141045 (Publication Type: Journal Article)
• Copyright: Copyright © 2020. Published by Elsevier Inc.

Chemical References

• Coumarins
• coumarin

Topics

• Animals
• Apoptosis (drug effects, physiology)
• Cells, Cultured
• Coumarins (chemistry, pharmacology, therapeutic use)
• Dose-Response Relationship, Drug
• Ischemic Stroke (drug therapy, metabolism, pathology)
• MAP Kinase Signaling System (drug effects, physiology)
• Male
• Mice
• Mice, Inbred C57BL
• Mitochondria (drug effects, metabolism, pathology)
• Oxidative Stress (drug effects, physiology)
• Phosphorylation (drug effects, physiology)