Danhong injection improves neurological function in rats with ischemic stroke by enhancing neurogenesis and activating BDNF/AKT/CREB signaling pathway
Danhong injection (DHI) is a traditional Chinese medicine injection that promotes blood circulation and removes blood stasis and has been widely used in the treatment of stroke. Many studies have focused on the mechanism of DHI in acute ischemic stroke (IS); however, few studies have thoroughly expl...
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Elsevier
2023-07-01
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Series: | Biomedicine & Pharmacotherapy |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223006777 |
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author | Lan Li Jie-hong Yang Chang Li Hui-fen Zhou Li Yu Xiao-long Wu Yi-hang Lu Yu He Hai-tong Wan |
author_facet | Lan Li Jie-hong Yang Chang Li Hui-fen Zhou Li Yu Xiao-long Wu Yi-hang Lu Yu He Hai-tong Wan |
author_sort | Lan Li |
collection | DOAJ |
description | Danhong injection (DHI) is a traditional Chinese medicine injection that promotes blood circulation and removes blood stasis and has been widely used in the treatment of stroke. Many studies have focused on the mechanism of DHI in acute ischemic stroke (IS); however, few studies have thoroughly explored its role during recovery. In this study, we aimed to determine the effect of DHI on long-term neurological function recovery after cerebral ischemia and explored the related mechanisms. Middle cerebral artery occlusion (MCAO) was used to establish an IS model in rats. The efficacy of DHI was assessed using neurological severity scores, behaviors, cerebral infarction volume and histopathology. Immunofluorescence staining was performed to assess hippocampal neurogenesis. An in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) cell model was constructed and western-blot analyses were performed to verify the underlying mechanisms. Our results showed that DHI treatment greatly reduced the infarct volume, promoted neurological recovery and reversed brain pathological changes. Furthermore, DHI promoted neurogenesis by increasing the migration and proliferation of neural stem cells, and enhancing synaptic plasticity. Moreover, we found that the pro-neurogenic effects of DHI were related to an increase in brain-derived neurotrophic factor (BDNF) expression and the activation of AKT/CREB, which were attenuated by ANA-12 and LY294002, the inhibitors of the BDNF receptor and PI3K. These results suggest that DHI improves neurological function by enhancing neurogenesis and activating the BDNF/AKT/CREB signaling pathways. |
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institution | Directory Open Access Journal |
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language | English |
last_indexed | 2024-03-13T10:03:02Z |
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series | Biomedicine & Pharmacotherapy |
spelling | doaj.art-4046b26e6f5d4ed3b808ec617ba7c6c52023-05-23T04:21:23ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-07-01163114887Danhong injection improves neurological function in rats with ischemic stroke by enhancing neurogenesis and activating BDNF/AKT/CREB signaling pathwayLan Li0Jie-hong Yang1Chang Li2Hui-fen Zhou3Li Yu4Xiao-long Wu5Yi-hang Lu6Yu He7Hai-tong Wan8Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang province, ChinaZhejiang Chinese Medical University, Hangzhou 310053, Zhejiang province, ChinaZhejiang Chinese Medical University, Hangzhou 310053, Zhejiang province, ChinaZhejiang Chinese Medical University, Hangzhou 310053, Zhejiang province, ChinaZhejiang Chinese Medical University, Hangzhou 310053, Zhejiang province, ChinaZhejiang Chinese Medical University, Hangzhou 310053, Zhejiang province, ChinaZhejiang Chinese Medical University, Hangzhou 310053, Zhejiang province, ChinaCorresponding authors.; Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang province, ChinaCorresponding authors.; Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang province, ChinaDanhong injection (DHI) is a traditional Chinese medicine injection that promotes blood circulation and removes blood stasis and has been widely used in the treatment of stroke. Many studies have focused on the mechanism of DHI in acute ischemic stroke (IS); however, few studies have thoroughly explored its role during recovery. In this study, we aimed to determine the effect of DHI on long-term neurological function recovery after cerebral ischemia and explored the related mechanisms. Middle cerebral artery occlusion (MCAO) was used to establish an IS model in rats. The efficacy of DHI was assessed using neurological severity scores, behaviors, cerebral infarction volume and histopathology. Immunofluorescence staining was performed to assess hippocampal neurogenesis. An in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) cell model was constructed and western-blot analyses were performed to verify the underlying mechanisms. Our results showed that DHI treatment greatly reduced the infarct volume, promoted neurological recovery and reversed brain pathological changes. Furthermore, DHI promoted neurogenesis by increasing the migration and proliferation of neural stem cells, and enhancing synaptic plasticity. Moreover, we found that the pro-neurogenic effects of DHI were related to an increase in brain-derived neurotrophic factor (BDNF) expression and the activation of AKT/CREB, which were attenuated by ANA-12 and LY294002, the inhibitors of the BDNF receptor and PI3K. These results suggest that DHI improves neurological function by enhancing neurogenesis and activating the BDNF/AKT/CREB signaling pathways.http://www.sciencedirect.com/science/article/pii/S0753332223006777Danhong injectionIschemic strokeNeurological functionNeurogenesisSynaptic plasticityBrain-derived neurotrophic factor |
spellingShingle | Lan Li Jie-hong Yang Chang Li Hui-fen Zhou Li Yu Xiao-long Wu Yi-hang Lu Yu He Hai-tong Wan Danhong injection improves neurological function in rats with ischemic stroke by enhancing neurogenesis and activating BDNF/AKT/CREB signaling pathway Biomedicine & Pharmacotherapy Danhong injection Ischemic stroke Neurological function Neurogenesis Synaptic plasticity Brain-derived neurotrophic factor |
title | Danhong injection improves neurological function in rats with ischemic stroke by enhancing neurogenesis and activating BDNF/AKT/CREB signaling pathway |
title_full | Danhong injection improves neurological function in rats with ischemic stroke by enhancing neurogenesis and activating BDNF/AKT/CREB signaling pathway |
title_fullStr | Danhong injection improves neurological function in rats with ischemic stroke by enhancing neurogenesis and activating BDNF/AKT/CREB signaling pathway |
title_full_unstemmed | Danhong injection improves neurological function in rats with ischemic stroke by enhancing neurogenesis and activating BDNF/AKT/CREB signaling pathway |
title_short | Danhong injection improves neurological function in rats with ischemic stroke by enhancing neurogenesis and activating BDNF/AKT/CREB signaling pathway |
title_sort | danhong injection improves neurological function in rats with ischemic stroke by enhancing neurogenesis and activating bdnf akt creb signaling pathway |
topic | Danhong injection Ischemic stroke Neurological function Neurogenesis Synaptic plasticity Brain-derived neurotrophic factor |
url | http://www.sciencedirect.com/science/article/pii/S0753332223006777 |
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