title: Brain-derived neurotrophic factor signalling mediates the antidepressant-like effect of piperine in chronically stressed mice.
abstract: Previous studies in our laboratory have demonstrated that piperine produced antidepressant-like action in various mouse models of behavioral despair. This study aimed to investigate the role of brain-derived neurotrophic factor (BDNF) signalling in the antidepressant-like effect of piperine in mice exposed to chronic unpredictable mild stress (CUMS). The results showed that CUMS caused depression-like behavior in mice, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. It was also found that BDNF protein expression in the hippocampus and frontal cortex were significantly decreased in CUMS-treated mice. Chronic treatment of piperine at the dose of 10mg/kg significantly ameliorated behavioural deficits of CUMS-treated mice in the sucrose preference test and forced swim test. Piperine treatment also significantly decreased immobility time in the forced swim test in naive mice. In parallel, chronic piperine treatment significantly increased BDNF protein expression in the hippocampus and frontal cortex of both naive and CUMS-treated mice. In addition, inhibition of BDNF signalling by injection of K252a, an inhibitor of the BDNF receptor TrkB, significantly blocked the antidepressant-like effect of piperine in the sucrose preference test and forced swim test of CUMS-treated mice. Taken together, this study suggests that BDNF signalling is an essential mediator for the antidepressant-like effect of piperine.
authors.affiliation: School of Chinese Medicine, The Chinese University of Hong Kong, Shatin N.T., Hong Kong; College of Pharmacy, Zhejiang Chinese Medicine University, Hangzhou, 310053, Zhejiang, China.
authors.forename: Qing-Qiu
authors.initials: QQ
authors.lastname: Mao
authors.affiliation: College of Pharmacy, Zhejiang Chinese Medicine University, Hangzhou, 310053, Zhejiang, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Huang
authors.affiliation: College of Pharmacy, Zhejiang Chinese Medicine University, Hangzhou, 310053, Zhejiang, China.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Zhong
authors.affiliation: School of Chinese Medicine, The Chinese University of Hong Kong, Shatin N.T., Hong Kong.
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Xian
authors.affiliation: School of Chinese Medicine, The Chinese University of Hong Kong, Shatin N.T., Hong Kong. Electronic address: paulip@cuhk.edu.hk.
authors.forename: Siu-Po
authors.initials: SP
authors.lastname: Ip
mesh_terms: D000470:Alkaloids / Q000627:therapeutic use*; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D052117:Benzodioxoles / Q000627:therapeutic use*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002227:Carbazoles / Q000494:pharmacology; D002908:Chronic Disease; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005518:Food Preferences / Q000187:drug effects; D026121:Indole Alkaloids / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010880:Piperidines / Q000627:therapeutic use*; D053284:Polyunsaturated Alkamides / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects*; D013315:Stress, Psychological / Q000188:drug therapy* / Q000378:metabolism*; D013395:Sucrose / Q000008:administration & dosage; D013549:Sweetening Agents / Q000008:administration & dosage; D013997:Time Factors
chemical_list: D000470:Alkaloids; D000928:Antidepressive Agents; D052117:Benzodioxoles; D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D013549:Sweetening Agents; D013395:Sucrose; C049985:staurosporine aglycone; C008922:piperine
keywords: Antidepressant; Brain-derived neurotrophic factor; Chronic unpredictable mild stress; Mice; Piperine