Neurovascular unit(NVU)is organized multi-cellular and multi-component networks that are essential for brain health and brain homeostasis maintaining.Neurovascular unit dysfunction is the central pathogenesis process of ischemic stroke.Thus integrated protection of NVU holds great therapeutic potential for ischemic stroke.Catalpol,classified into the iridoid monosaccharide glycoside,is the main active ingredient of the radix from traditional Chinese medicine,Rehmannia glutinosa Libosch,that exhibits protective effects in several brain-related diseases.In the present study,we investigated whether catalpol exerted protective effects for NVU in ischemic stroke and the underlying mechanisms.MCAO rats were administered catalpol(2.5,5.0,10.0 mg·kg-1·d-1,i.v.)for 14 days.We showed that catalpol treatment dose-dependently reduced the infarction volume and significantly attenuated neurological deficits score in MCAO rats.Furthermore,catalpol treatment significantly ameliorated impaired NVU in ischemic region by protecting vessel-neuron-astrocyte structures and morphology,and promoting angiogenesis and neurogenesis to replenish lost vessels and neurons.Moreover,catalpol treatment significantly increased the expression of vascular endothelial growth factor(VEGF)through up-regulating PI3K/AKT signaling,followed by increasing FAK and Paxillin and activating PI3K/AKT and MEK1/2/ERK1/2 pathways.The protective mechanisms of catalpol were confirmed in an in vitro three-dimensional NVU model subjected to oxygen-glucose deprivation.In conclusion,catalpol protects NVU in ischemic region via activation of PI3K/AKT signaling and increased VEGF production;VEGF further enhances PI3K/AKT and MEK1/2/ERK1/2 signaling,which may trigger a partly feed-forward loop to protect NVU from ischemic stroke.

Hong-jin Wang;Hai-feng Ran;Yue Yin;Xiao-gang Xu;Bao-xiang Jiang;Shi-qi Yu;Yi-jin Chen;Hui-jing Ren;Shan Feng;Ji-fen Zhang;Yi Chen;Qiang Xue;Xiao-yu Xu

College of Pharmaceutical Sciences&Chinese Medicine,Southwest University,Chongqing 400715,China;Chongqing Key Laboratory of New Drug Screening from Traditional Chinese Medicine,Chongqing 400715,China;Pharmacology of Chinese Materia Medica-the Key Discipline Constructed by the State Administration of Traditional Chinese Medicine,Chongqing 400715,China;Chongqing Medical and Pharmaceutical College,Chongqing 401331,China;Southwest University Hospital,Chongqing 400715,China

中国药理学报（英文版）

[1]Hong-jin Wang;Hai-feng Ran;Yue Yin;Xiao-gang Xu;Bao-xiang Jiang;Shi-qi Yu;Yi-jin Chen;Hui-jing Ren;Shan Feng;Ji-fen Zhang;Yi Chen;Qiang Xue;Xiao-yu Xu-.Catalpol improves impaired neurovascular unit in ischemic stroke rats via enhancing VEGF-PI3K/AKT and VEGF-MEK1/2/ERK1/2 signaling)[J].中国药理学报（英文版）,2022(07):1670-1685

Catalpol,iridoid,catalpol

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