title: Lyophilized Powder of Catalpol and Puerarin Protected Cerebral Vessels from Ischemia by Its Anti-apoptosis on Endothelial Cells.
abstract: Catalpol and puerarin are two monomers ofRehmannia glutinosaandLobed Kudzuvine Root, which are two herbs commonly used together in ancient prescriptions of traditional Chinese medicine for cerebral ischemia. Our previous study shows that the lyophilized powder of the two monomers improved the outcome of cerebral ischemia excellently in rodents. However, if it protects vessels from ischemia is unknown. The present research studied the protection of lyophilized powder of catalpol and puerarin (CP) on endothelial cells and the relative mechanismin vivoandin vitro. Middle cerebral artery occlusion (MCAO) rats were used to study the improvement of CP on neurological deficiency, regional cerebral blood flow (rCBF), and infarct volume. The morphology of vessels and the apoptosis of brain vascular endothelial cells (BVECs) were observed and detected by immunohistochemistry approaches. To study how CP protected primary BVECs (pBVECs) from ischemic penumbra, oxygen glucose deprivation (OGD)-damaged pBVECs were cultured in the condition of insufficient nutrition and low oxygen which recapitulate the low perfusion of ischemic penumbra. Using the cell model, the mechanism by which CP protected pBVECs was studied by shRNA and pathway inhibitors. CP at the dose of 65.4 mg/kg increased regional cerebral blood flow (rCBF), reduced infarct volume, protected vessel integrity and inhibited endothelial cell apoptosisin vivo. But it only improved rCBF, vessel integrity and BVECs apoptosis at the dose of 32.7 mg/kg.In vitro, the protection of CP on pBVECs was proved to be ERK/HIF-1a- and PI3K/AKT/mTOR/HIF-1a-dependent. This study indicates a possibility of CP being a new drug for cerebral ischemia. Besides, this research provides an alternative cell model for penumbra ECs study.
authors.affiliation: College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing 400715, China; Institute of Chinese Medicine, Southwest University, Chongqing 400715, China; Chongqing Engineering Research Centre for Pharmacological Evaluation, Chongqing 400715, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing 400715, China; Institute of Chinese Medicine, Southwest University, Chongqing 400715, China; Chongqing Engineering Research Centre for Pharmacological Evaluation, Chongqing 400715, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Tang
authors.affiliation: College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing 400715, China; Institute of Chinese Medicine, Southwest University, Chongqing 400715, China; Chongqing Engineering Research Centre for Pharmacological Evaluation, Chongqing 400715, China.
authors.forename: Siying
authors.initials: S
authors.lastname: Shao
authors.affiliation: College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing 400715, China; Institute of Chinese Medicine, Southwest University, Chongqing 400715, China; Chongqing Engineering Research Centre for Pharmacological Evaluation, Chongqing 400715, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Faculty of Psychology, Southwest University, Chongqing, 400715, China.
authors.forename: Weihai
authors.initials: W
authors.lastname: Chen
authors.affiliation: College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing 400715, China; Institute of Chinese Medicine, Southwest University, Chongqing 400715, China; Chongqing Engineering Research Centre for Pharmacological Evaluation, Chongqing 400715, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism; D057888:Iridoid Glucosides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D010100:Oxygen / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D032267:Rehmannia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D057888:Iridoid Glucosides; D007529:Isoflavones; D018696:Neuroprotective Agents; D034741:RNA, Small Interfering; C078040:catalpol; D005947:Glucose; D010100:Oxygen; C033607:puerarin
keywords: Catalpol; Endothelial cell; Puerarin; apoptosis; cerebral ischemia; vessel