Exposure-Response Analysis and Mechanism of Ginkgolide B’s Neuroprotective Effect in Acute Cerebral Ischemia/Reperfusion Stage in Rat
| Autor: | Dake, Cai, Zhongxing, Luo, Jiyan, Su, Haining, Gan, Zhi, Wang, Xiaolin, Liu, Siyi, Li, Jingjing, Wu, Jiangying, Chen, Renqiang, Ma, Min, Huang, Guoping, Zhong |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Biological and Pharmaceutical Bulletin. 45:409-420 |
| ISSN: | 1347-5215 0918-6158 |
| DOI: | 10.1248/bpb.b21-00781 |
| Popis: | Ginkgolide B (GKB) is a well-established neuroprotectant for acute ischemia stroke. However, its cerebral exposure and real-time response remain elusive in acute ischemia/reperfusion stage, and it hinders its usage in therapeutic window of ischemia stroke. Therefore, we investigate the exposure-response relationship of GKB (10 mg/kg, intravenously (i.v.)) as well as its neuroprotective mechanism in acute ischemia/reperfusion rats. Cerebral and plasma exposure of GKB is comparatively explored in both of normal rats and acute ischemia/reperfusion rats. Correspondingly, neurological function and brain jury indexes were assessed at each time point, and superoxide dismutase (SOD), malondialdehyde (MDA), platelet activator factor (PAF) and thromboxane A2 (TXA2) are indexed as pharmacological response to GKB. Exposure-response relationships are analyzed by using linear regression. Additionally, cerebral expressions of proteins in PAF-regulated pathways are tested at each time point. Results show cerebral and plasma concentrations of GKB are much higher in acute ischemia/reperfusion rats than those in normal rats. Cerebral infarction, neurological function (NF) score, abnormal PAF and excessive MDA are significantly alleviated in 24 h after GKB injection, and PAF is reduced in exposure-response manner with significant concentration-response relationship (R |
| Databáze: | OpenAIRE |
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