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Sci Rep. 2017 Aug 30;7(1):10052. doi: 10.1038/s41598-017-10283-4.

(S)-Oxiracetam is the Active Ingredient in Oxiracetam that Alleviates the Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion in Rats.

Li W1,2, Liu H3, Jiang H1,2, Wang C1,2, Guo Y1,2, Sun Y1,2, Zhao X1,2, Xiong X4, Zhang X4, Zhang K1,2, Nie Z5, Pu X6,7.

Author information

1
National Key Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, P. R. China.
2
Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, P. R. China.
3
Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.
4
Department of Pharmacy, Peking University Third Hospital, Beijing, 100191, P. R. China.
5
Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China. znie@iccas.ac.cn.
6
National Key Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, P. R. China. 11956170@pku.edu.cn.
7
Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, P. R. China. 11956170@pku.edu.cn.

Abstract

Chronic cerebral hypoperfusion is a pathological state that is associated with the cognitive impairments in vascular dementia. Oxiracetam is a nootropic drug that is commonly used to treat cognitive deficits of cerebrovascular origins. However, oxiracetam is currently used as a racemic mixture whose effective ingredient has not been identified to date. In this study, we first identified that (S)-oxiracetam, but not (R)-oxiracetam, was the effective ingredient that alleviated the impairments of spatial learning and memory by ameliorating neuron damage and white matter lesions, increasing the cerebral blood flow, and inhibiting astrocyte activation in chronic cerebral hypoperfused rats. Furthermore, using MALDI-MSI and LC-MS/MS, we demonstrated that (S)-oxiracetam regulated ATP metabolism, glutamine-glutamate and anti-oxidants in the cortex region of hypoperfused rats. Altogether, our results strongly suggest that (S)-oxiracetam alone could be a nootropic drug for the treatment of cognitive impairments caused by cerebral hypoperfusion.

PMID:
28855592
PMCID:
PMC5577264
DOI:
10.1038/s41598-017-10283-4
[Indexed for MEDLINE]
Free PMC Article

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