Abstract
Salvianolate lyophilized injection (SLI) and Xueshuantong injection (lyophilized) (XST) are two herbal standardized preparations that have been widely used in China for the treatment of acute cerebral infarction. In this study, we investigated the neuroprotective effects of SLI combined with XST in a rat model of middle cerebral artery occlusion-reperfusion (MCAO/R). Wistar rats were subjected to 1.5 h of MCAO followed by reperfusion for 3 h, then were treated with SLI or XST alone, or with their combinations via tail vein injection daily for 3 d. Edaravone (EDI, 6 mg·kg−1·d−1) was used as a positive control drug, We showed that administration of a combination of 1X1S (XST 100 mg·kg−1·d−1 plus SLI 21 mg·kg−1·d−1) more effectively protected the ischemic brains than SLI or XST used alone. Administration of 1X1S not only significantly decreased neurological deficit scores and infarct volumes and increased regional cerebral blood flow, but also inhibited the activation of both microglia and astrocytes in the hippocampus. Furthermore, administration of 1X1S significantly decreased the levels of MDA and ROS with concomitant increases in the levels of antioxidant activity (SOD, CAT and GSH) in the brain tissues as compared with SLI and XST used alone. Moreover, administration of 1X1S remarkably upregulated the expression of Nrf-2, HO-1 and NQO-1, and downregulated the expression of Keap1 and facilitated the nuclear translocation of Nrf-2 in the brain tissues as compared with XST used alone. Our study demonstrates that a combination of 1X1S effectively protects MCAO/R injury via suppressing oxidative stress and the Nrf-2/Keap1 pathway.
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Acknowledgements
This study was supported by the Major New Drugs Innovation and Development (2012zx09101202), the National Natural Sciences Foundation of China (8157140605 and 815740052), the Natural Science Foundation of Tianjin (14JCYBJC28900), the Tianjin Technology Innovation System and the Condition of Platform Construction Plan (16PTSYJC00120).
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Wang, Fj., Wang, Sx., Chai, Lj. et al. Xueshuantong injection (lyophilized) combined with salvianolate lyophilized injection protects against focal cerebral ischemia/reperfusion injury in rats through attenuation of oxidative stress. Acta Pharmacol Sin 39, 998–1011 (2018). https://doi.org/10.1038/aps.2017.128
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DOI: https://doi.org/10.1038/aps.2017.128
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