title: Umbelliferone reverses depression-like behavior in chronic unpredictable mild stress-induced rats by attenuating neuronal apoptosis via regulating ROCK/Akt pathway.
abstract: There is increasing evidence that major depressive disorder (MDD) is also a progressive neurodegeneration disorder and neuronal damage is the major pathology of MDD. Umbelliferone, a coumarin derivative, was found in a range of plants with proved anti-oxidative, anti-inflammatory and neuroprotective effects. The primary purpose of this investigation was to evaluate whether umbelliferone could confer an antidepressant-like effect on the depressive model in rats developed by chronic unpredictable mild stress (CUMS) and explore the possible mechanism involved in its neuroprotective effects. We found that treatments with umbelliferone (15mg/kg, 30mg/kg) significantly ameliorated CUMS-induced depressive-like behaviors, such as decreased sucrose consumption, reduced locomotor activity and prolonged immobility time. Rats under CUMS stimulation treated with umbelliferone (15mg/kg, 30mg/kg) showed reduced neuronal apoptosis, as well as inhibited inflammatory cytokines levels by down-regulating Rho-associated protein kinase (ROCK) signaling and up-regulating protein kinase B (Akt) signaling. In conclusion, umbelliferone showed neuroprotective effects on CUMS-induced model of depression, which was associated with the inhibition of neuronal apoptosis modulated by ROCK/Akt pathway.
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Qin
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Meiting
authors.initials: M
authors.lastname: Song
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Ruipeng
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: mazhanqiang0427@163.com.
authors.forename: Zhanqiang
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: spma@cpu.edu.cn.
authors.forename: Shiping
authors.initials: S
authors.lastname: Ma
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D003863:Depression / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005106:Exploratory Behavior; D005518:Food Preferences; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013315:Stress, Psychological / Q000150:complications; D013395:Sucrose / Q000008:administration & dosage; D013550:Swimming / Q000523:psychology; D014468:Umbelliferones / Q000627:therapeutic use*; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D014468:Umbelliferones; D013395:Sucrose; C031477:7-hydroxycoumarin; D051058:Oncogene Protein v-akt; D054460:rho-Associated Kinases
keywords: Chronic unpredictable mild stress; Depression; Neuronal apoptosis; ROCK/Akt pathway; Umbelliferone