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.

高良姜 氧化叶Miq。（AOM）是用于改善中风后卒中治疗的认知功能的草药，但其功效和潜在机制尚不清楚。在本研究中，我们测试了AOM可以诱导成人海马神经发生并改善中风后认知障碍的假设通过诱导脑源性神经营养因子（BDNF）信号通路。为了检验假设，我们执行了两个体内 使用短暂性大脑中动脉闭塞（MCAO）模型的大鼠实验和 体外神经干细胞（NSC）实验，使用氧葡萄糖剥夺加复氧。首先，AOM治疗可显着上调海马中BDNF，原霉素受体激酶B（TrkB）和磷酸化AKT（p-AKT）的表达，增强成年海马神经发生，并改善其空间学习/记忆和认知功能MCAO后缺血大鼠体内。下一个，体外 研究证实 p-香豆酸（P-CA）是从AOM提取物中鉴定出的最有效的化合物，具有激活BDNF / TrkB / AKT信号传导途径和促进NSC增殖的特性。BDNF / TrkB特异性抑制剂ANA12的共同治疗消除了P-CA诱导BDNF / TrkB / AKT活化和NSC增殖的作用。最后，动物实验表明，P-CA处理可增强短暂MCAO缺血大鼠海马神经元的增殖和分化，改善空间学习和记忆功能，并减轻其焦虑。总之，P-CA是AOM的代表化合物，具有激活BDNF / TrkB / AKT信号通路，促进海马神经发生，改善认知功能和减轻缺血性中风后大鼠焦虑的生物活性。