Pretreatment with Danhong injection protects the brain against ischemia-reperfusion injury
Shaoxia Wang1, Hong Guo2, Xumei Wang1, Lijuan Chai1, Limin Hu1, Tao Zhao3, Buchang Zhao3, Xiaoxu Tan2, Feifei Jia2
1 Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
2 Tianjin Key Laboratory of Chinese Medicine Pharmacology, Tianjin University of Traditional Chinese Medicine, Tianjin, China
3 Buchang Pharmaceutical Co., Ltd., Xi'an, Shaanxi Province, China
Ph.D., Tianjin State Key Laboratory of Modern Chinese Medicine, Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin 300193
Source of Support: This study was supported by the National Natural Science Foundation of China, No. 81173592; National Science and Technology Major Project of the Ministry of Science and Technology of China, No. 2011ZX09201-201, 2012ZX09101201-004, 2012ZX09101202, NCET-13-0935, 2013ZX09201020; Tianjin Municipal Applied Basic Research and Cutting-Edge Technology Research Scheme of China, No. 14JCYBJC28900; and Program for Innovation Team Training in Universities in Tianjin, No. TD12-5035., Conflict of Interest: None
Danhong injection (DHI), a Chinese Materia Medica standardized product extracted from Radix Salviae miltiorrhizae and Flos Carthami tinctorii, is widely used in China for treating acute ischemic stroke. In the present study, we explored the neuroprotective efficacy of DHI in a rat model of temporary middle cerebral artery occlusion, and evaluated the potential mechanisms underlying its effects. Pretreatment with DHI (0.9 and 1.8 mL/kg) resulted in a significantly smaller infarct volume and better neurological scores than pretreatment with saline. Furthermore, DHI significantly reduced the permeability of the blood-brain barrier, increased occludin protein expression and decreased neutrophil infiltration, as well as profoundly suppressing the upregulation of matrix metallopeptidase-9 expression seen in rats that had received vehicle. Matrix metallopeptidase-2 expression was not affected by ischemia or DHI. Moreover, DHI (1.8 mL/kg) administered 3 hours after the onset of ischemia also improved neurological scores and reduced infarct size. Our results indicate that the neuroprotective efficacy of DHI in a rat model of cerebral ischemia-reperfusion injury is mediated by a protective effect on the blood-brain barrier and the reversal of neutrophil infiltration.