Journal
LIFE SCIENCES
Volume 264, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2020.118499
Keywords
Ischemic stroke; Biscoumarin derivative; Oxidative damage; Apoptosis; Cerebral ischemic reperfusion injury
Funding
- Shaanxi Science and Technology Innovation Project [KTCL0303]
- Science and Technology Department, Shaanxi Province
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The novel biscoumarin derivative Comp. B has been shown to alleviate mitochondrial oxidative damage and apoptosis in ischemic stroke models, improving neurobehavioral outcomes in mice and suggesting its potential as a treatment for ischemic stroke.
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 mu g/ml and the optimal protective concentration was 20 mu g/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.
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