TY - JOUR
T1 - Alpinia oxyphylla Miq. and Its Active Compound P-Coumaric Acid Promote Brain-Derived Neurotrophic Factor Signaling for Inducing Hippocampal Neurogenesis and Improving Post-cerebral Ischemic Spatial Cognitive Functions
AU - He, Yacong
AU - Chen, Shuang
AU - Tsoi, Bun
AU - Qi, Shuhua
AU - Gu, Bing
AU - Wang, Zhenxing
AU - Peng, Cheng
AU - Shen, Jiangang
N1 - Funding Information:
This work was supported by the grant of Areas of Excellence Scheme 2016/17, Research Grants Council, Hong Kong SAR (JS, AoE/P-705/16), General Research Fund (GRF), Research Grants Council, Hong Kong SAR (JS, no.17118717), Seed Fund for Basic Research, University of Hong Kong (JS, no. 201811159037), and State Key Project for Joint Region Innovation Development Scheme, National Natural Science Foundation of China (CP, U19A2010).
Funding Information:
We thank Faculty Core Facility, Li Ka Shing Faculty of Medicine, the University of Hong Kong to supply Carl Zeiss LSM 800 for capturing confocal fluorescent images and GE6500 for high content screening study. Funding. This work was supported by the grant of Areas of Excellence Scheme 2016/17, Research Grants Council, Hong Kong SAR (JS, AoE/P-705/16), General Research Fund (GRF), Research Grants Council, Hong Kong SAR (JS, no.17118717), Seed Fund for Basic Research, University of Hong Kong (JS, no. 201811159037), and State Key Project for Joint Region Innovation Development Scheme, National Natural Science Foundation of China (CP, U19A2010).
Publisher Copyright:
© Copyright © 2021 He, Chen, Tsoi, Qi, Gu, Wang, Peng and Shen.
PY - 2021/1/18
Y1 - 2021/1/18
N2 - Alpinia oxyphylla Miq. (AOM) is a medicinal herb for improving cognitive functions in traditional Chinese medicine for poststroke treatment, but its efficacies and underlying mechanisms remain unknown. In the present study, we tested the hypothesis that AOM could induce adult hippocampal neurogenesis and improve poststroke cognitive impairment via inducing brain-derived neurotrophic factor (BDNF) signaling pathway. In order to test the hypothesis, we performed both in vivo rat experiments using transient middle cerebral artery occlusion (MCAO) model and in vitro neural stem cell (NSC) experiments using oxygen–glucose deprivation plus reoxygenation. First, AOM treatment significantly up-regulated the expression of BDNF, tropomycin receptor kinase B (TrkB), and phosphorylated AKT (p-AKT) in the hippocampus, enhanced adult hippocampal neurogenesis, and improved the spatial learning/memory and cognitive functions in the post-MCAO ischemic rats in vivo. Next, in vitro studies confirmed p-coumaric acid (P-CA) to be the most effective compound identified from AOM extract with the properties of activating BDNF/TrkB/AKT signaling pathway and promoting NSC proliferation. Cotreatment of BDNF/TrkB-specific inhibitor ANA12 abolished the effects of P-CA on inducing BDNF/TrkB/AKT activation and the NSC proliferation. Finally, animal experiments showed that P-CA treatment enhanced the neuronal proliferation and differentiation in the hippocampus, improved spatial learning and memory functions, and reduced anxiety in the transient MCAO ischemic rats. In conclusion, P-CA is a representative compound from AOM for its bioactivities of activating BDNF/TrkB/AKT signaling pathway, promoting hippocampal neurogenesis, improving cognitive functions, and reducing anxiety in post–ischemic stroke rats.
AB - Alpinia oxyphylla Miq. (AOM) is a medicinal herb for improving cognitive functions in traditional Chinese medicine for poststroke treatment, but its efficacies and underlying mechanisms remain unknown. In the present study, we tested the hypothesis that AOM could induce adult hippocampal neurogenesis and improve poststroke cognitive impairment via inducing brain-derived neurotrophic factor (BDNF) signaling pathway. In order to test the hypothesis, we performed both in vivo rat experiments using transient middle cerebral artery occlusion (MCAO) model and in vitro neural stem cell (NSC) experiments using oxygen–glucose deprivation plus reoxygenation. First, AOM treatment significantly up-regulated the expression of BDNF, tropomycin receptor kinase B (TrkB), and phosphorylated AKT (p-AKT) in the hippocampus, enhanced adult hippocampal neurogenesis, and improved the spatial learning/memory and cognitive functions in the post-MCAO ischemic rats in vivo. Next, in vitro studies confirmed p-coumaric acid (P-CA) to be the most effective compound identified from AOM extract with the properties of activating BDNF/TrkB/AKT signaling pathway and promoting NSC proliferation. Cotreatment of BDNF/TrkB-specific inhibitor ANA12 abolished the effects of P-CA on inducing BDNF/TrkB/AKT activation and the NSC proliferation. Finally, animal experiments showed that P-CA treatment enhanced the neuronal proliferation and differentiation in the hippocampus, improved spatial learning and memory functions, and reduced anxiety in the transient MCAO ischemic rats. In conclusion, P-CA is a representative compound from AOM for its bioactivities of activating BDNF/TrkB/AKT signaling pathway, promoting hippocampal neurogenesis, improving cognitive functions, and reducing anxiety in post–ischemic stroke rats.
KW - Alpinia oxyphyllaMiq
KW - brain-derived neurotrophic factor
KW - hippocampal neurogenesis
KW - ischemic stroke
KW - p-coumaric acid
UR - http://www.scopus.com/inward/record.url?scp=85100571423&partnerID=8YFLogxK
U2 - 10.3389/fcell.2020.577790
DO - 10.3389/fcell.2020.577790
M3 - Journal article
AN - SCOPUS:85100571423
SN - 2296-634X
VL - 8
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
M1 - 577790
ER -