title: 2-(3',5'-Dimethoxybenzylidene) cyclopentanone, a novel synthetic small-molecule compound, provides neuroprotective effects against ischemic stroke.
abstract: 2-(3',5'-Dimethoxybenzylidene) cyclopentanone (DMBC) is a novel small-molecule compound synthesized by our group. Here, we found that in rat models of permanent middle cerebral artery occlusion (pMCAO), intraperitoneal injection (ip) of DMBC at 1h after ischemia reduced infarct volume, improved neurological deficits and increased the protein levels of microtubule-associated protein 2 (MAP 2) and glial fibrillary acid protein (GFAP) in the ischemic cortex. Post-treatment of DMBC still produced neuroprotective effects even when administered at 6h after ischemia. In the oxygen-glucose deprivation (OGD)-induced astrocytes or HT22 cell injury, DMBC treatment decreased the OGD-induced lactate dehydrogenase (LDH) leakage and increased the GFAP levels in astrocytes. In addition, Annexin-V-Fluos staining analysis revealed that DMBC treatment attenuated both OGD-induced apoptosis and necrosis in astrocytes. Western blotting analysis showed DMBC treatment inhibited the ischemia or OGD-induced increases in active cathepsin B in the ischemic cortex or in astrocytes or HT22 cells. Immunofluorescence analysis demonstrated that DMBC treatment blocked the ischemia or OGD-induced release of cathepsin B from the lysosomes into the cytoplasm in the ischemic cortex or in astrocytes or HT22 cells. Taken together, our results indicate that DMBC can offer neuroprotective effects against cerebral ischemia with an extended therapeutic window and its mechanism might be associated with inhibition of the cathepsin B activation.
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Department of Pharmacology, Laboratory of Cerebrovascular Pharmacology, College of Pharmaceutical Science, Soochow University, Suzhou 215123, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou 215123, China.
authors.forename: W W
authors.initials: WW
authors.lastname: Gu
authors.affiliation: Department of Emergency, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors.forename: S Q
authors.initials: SQ
authors.lastname: Lu
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Department of Pharmacology, Laboratory of Cerebrovascular Pharmacology, College of Pharmaceutical Science, Soochow University, Suzhou 215123, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou 215123, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Ni
authors.affiliation: Guangzhou Institute of Traumatic Surgery, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou 510220, China.
authors.forename: Z H
authors.initials: ZH
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Department of Pharmacology, Laboratory of Cerebrovascular Pharmacology, College of Pharmaceutical Science, Soochow University, Suzhou 215123, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou 215123, China.
authors.forename: X Y
authors.initials: XY
authors.lastname: Zhou
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Department of Pharmacology, Laboratory of Cerebrovascular Pharmacology, College of Pharmaceutical Science, Soochow University, Suzhou 215123, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou 215123, China.
authors.forename: Y M
authors.initials: YM
authors.lastname: Zhu
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Department of Pharmacology, Laboratory of Cerebrovascular Pharmacology, College of Pharmaceutical Science, Soochow University, Suzhou 215123, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou 215123, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Department of Pharmacology, Laboratory of Cerebrovascular Pharmacology, College of Pharmaceutical Science, Soochow University, Suzhou 215123, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou 215123, China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Department of Pharmacology, Laboratory of Cerebrovascular Pharmacology, College of Pharmaceutical Science, Soochow University, Suzhou 215123, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou 215123, China.
authors.forename: L S
authors.initials: LS
authors.lastname: Li
authors.affiliation: The Second High School Attached to Beijing Normal University, Beijing 100091, China.
authors.forename: W Z
authors.initials: WZ
authors.lastname: Sun
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Department of Pharmacology, Laboratory of Cerebrovascular Pharmacology, College of Pharmaceutical Science, Soochow University, Suzhou 215123, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou 215123, China. Electronic address: huilingzhang07@hotmail.com.
authors.forename: H L
authors.initials: HL
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Department of Pharmacology, Laboratory of Cerebrovascular Pharmacology, College of Pharmaceutical Science, Soochow University, Suzhou 215123, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou 215123, China. Electronic address: aoguizhen@suda.edu.cn.
authors.forename: G Z
authors.initials: GZ
authors.lastname: Ao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects; D001597:Benzylidene Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003517:Cyclopentanes / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005947:Glucose / Q000172:deficiency; D000860:Hypoxia; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology; D053580:Muscle Strength / Q000187:drug effects; D009460:Neurologic Examination; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: C000589425:2-(3',5'-dimethoxybenzylidene)cyclopentanone; D001597:Benzylidene Compounds; D003517:Cyclopentanes; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D005947:Glucose
keywords: 2-(3′,5′-Dimethoxybenzylidene) cyclopentanone; HT 22 cell; astrocyte; cathepsin B; cerebral ischemia; neuroprotection