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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Main Authors: Lan Li, Jie-hong Yang, Chang Li, Hui-fen Zhou, Li Yu, Xiao-long Wu, Yi-hang Lu, Yu He, Hai-tong Wan
Format: Article
Language:English
Published: Elsevier 2023-07-01
Series:Biomedicine & Pharmacotherapy
Subjects:
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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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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