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Danhong Injection Attenuates Ischemia/Reperfusion-Induced Brain Damage Which is Associating with Nrf2 Levels In Vivo and In Vitro

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Abstract

Danhong injection, a Chinese Materia Medica standardized product extracted from Radix Salviae miltiorrhizae and Flos Carthami tinctorii, is used extensively for the treatment of cerebrovascular diseases such as acutely cerebral infarction in clinic. In this study, we further investigated the mechanisms of Danhong injection on cerebral ischemia/reperfusion (I/R) damage relating to Nrf2/ARE signalling pathway in vivo and in vitro. For in vivo experiment, cerebral I/R injury was induced through middle cerebral artery occlusion. Rats were randomly divided into five groups: sham-operated group, I/R injury group, 6 mg/kg edaravone injection (positive control drug) group, 0.9 ml/kg Danhong injection (DHI-L) group, 1.8 ml/kg Danhong injection (DHI-H) group. The neurological score, cerebral infarction and brain edema were assessed while levels of superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) in brain tissue were also evaluated. Transcription levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase 1 (NQO1) were analysed by real-time polymerase chain reaction. For in vitro experiment, mouse Neuro-2A cells were wounded with H2O2 then cell viability and mRNA transcriptions levels of Nrf2, HO-1, NQO1 were detected. Protein expression level of Nrf2 was assayed by western blotting. The results showed that Danhong injection could ameliorate neurological score, cerebral infarction and brain edema. Also it can increase levels of SOD, GSH and decrease of MDA and upregulate expressions of Nrf2, HO-1, NQO1 in ischemic brain tissue in vivo. What’s more, it increased the mRNA transcription of Nrf2 and HO-1 and upregulated protein expression of Nrf2 in vitro. These findings suggested that Danhong injection could prevent I/R-induced brain damage through activating Nrf2/ARE signaling pathway.

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Acknowledgments

This research was supported by the Technology Major Projects (2012ZX09101201-004, 2011ZX09201, 2012ZX09101202) and Specialized Research Fund for the Doctoral Program of Higher Education (20121210120005), Program for Changjiang Scholars and Innovative Research Team in University.

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  1. Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin Key Laboratory of Traditional Chinese Medicine Pharmacology, #312 Anshan xi road, Nankai district, Tianjin, 300193, China

    Hong Guo, Mei-jiao Li, Qing-qing Liu, Li-li Guo, Meng-meng Ma, Shao-xia Wang, Bin Yu & Li-Min Hu

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  1. Hong Guo
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  2. Mei-jiao Li
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  3. Qing-qing Liu
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Correspondence to Li-Min Hu.

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Guo, H., Li, Mj., Liu, Qq. et al. Danhong Injection Attenuates Ischemia/Reperfusion-Induced Brain Damage Which is Associating with Nrf2 Levels In Vivo and In Vitro. Neurochem Res 39, 1817–1824 (2014). https://doi.org/10.1007/s11064-014-1384-1

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  • DOI: https://doi.org/10.1007/s11064-014-1384-1

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