Antidepressant like effects of piperine in chronic mild stress treated mice and its possible mechanisms.
In this study, we investigated the antidepressant-like effect of piperine in mice exposed to chronic mild stress (CMS) procedure. Repeated administration of piperine for 14 days at the doses of 2.5, 5 and 10 mg/kg reversed the CMS-induced changes in sucrose consumption, plasma corticosterone level and open field activity. Furthermore, the decreased proliferation of hippocampal progenitor cells was ameliorated and the level of brain-derived neurotrophic factor (BDNF) in hippocampus of CMS stressed mice was up-regulated by piperine treatment in the same time course. In addition, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactic dehydrogenase (LDH) assays showed that piperine (6.25-25 microM) or fluoxetine (FLU, 1 microM) dose-dependently protected primary cultured hippocampal neurons from the lesion induced by 10 microM corticosterone (CORT). Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the messenger ribonucleic acid (mRNA) level of BDNF in cultured neurons. Treatment with piperine (6.25-25 microM) for 72 h reversed the CORT-induced reduction of BDNF mRNA expression in cultured hippocampal neurons. In summary, up-regulation of the progenitor cell proliferation of hippocampus and cytoprotective activity might be mechanisms involved in the antidepressant-like effect of piperine, which may be closely related to the elevation of hippocampal BDNF level.
Li
Song
S
Laboratory for Brain and Mind, Institute of Neuroinformatics, Dalian University of Technology, Dalian, 116023,China. lisong_spu2005@yahoo.com
Wang
Che
C
Wang
Minwei
M
Li
Wei
W
Matsumoto
Kinzo
K
Tang
Yiyuan
Y
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents; D052117:Benzodioxoles / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002908:Chronic Disease; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology; D003863:Depression / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology*; D006624:Hippocampus / Q000473:pathology; D007150:Immunohistochemistry; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000187:drug effects; D013315:Stress, Psychological / Q000150:complications* / Q000473:pathology / Q000523:psychology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D015430:Weight Gain
D000470:Alkaloids; D000928:Antidepressive Agents; D052117:Benzodioxoles; D019208:Brain-Derived Neurotrophic Factor; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D013778:Tetrazolium Salts; D013844:Thiazoles; D007770:L-Lactate Dehydrogenase; C022616:thiazolyl blue; C008922:piperine; D003345:Corticosterone