title: Piper sarmentosum Roxb. produces antidepressant-like effects in rodents, associated with activation of the CREB-BDNF-ERK signaling pathway and reversal of HPA axis hyperactivity.
abstract: BACKGROUND
  There are many plants of genus Piper which have been reported to induce antidepressant-like effects, Piper sarmentosum (PS) is one of them. PS is a Chinese herbal medicine and a traditional edible vegetable.
  
  
  METHODS
  In the present study, the antidepressant-like effects of PS extracts and the ethyl acetate fraction of PS extracts (PSY) were assessed using the open field test (OFT), forced swimming test (FST), and tail suspension test (TST) in mice. Furthermore, we applied a 4 consecutive weeks of chronic unpredictable mild stress (CUMS) as a model of depression in rats, followed by a sucrose preference test. Then we examined the possible mechanisms of this action. The activity of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by detecting the serum corticosterone (CORT) concentrations, and the protein expression levels of brain-derived neurotrophic factor (BDNF), the phosphorylated form CREB and ERK1/2 were detected by qRT-PCR or Western blot.
  
  
  RESULTS
  The results showed that PS extracts (100, 200mg/kg) and PSY (12.5, 25, 50mg/kg) treatment produced antidepressant-like effects in mice similar to fluoxetine (20mg/kg), indicated by the reduced immobility time in the FST and TST, while both had no influence on the locomotor activity in the OFT. PSY treatment significantly increased sucrose preference and reduced serum CORT levels in CUMS rats. Moreover, PSY up-regulated BDNF protein levels, and increased CREB and ERK phosphorylation levels in the hippocampus on CUMS rats.
  
  
  CONCLUSIONS
  These findings suggest that the antidepressant-like effects of PS extracts and PSY are mediated, at least in part, by modulating HPA axis, BDNF, CREB and ERK phosphorylation and expression in the hippocampus.
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, PR China; The 102nd Hospital of PLA, 55 Heping North Road, Changzhou 213003, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: The 102nd Hospital of PLA, 55 Heping North Road, Changzhou 213003, PR China.
authors.forename: Fa-Lin
authors.initials: FL
authors.lastname: Qu
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, PR China.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Jiang
authors.affiliation: Faculty of Science, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool L3 3AF, UK.
authors.forename: Khalid
authors.initials: K
authors.lastname: Rahman
authors.affiliation: Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7568, United States.
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, PR China; Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7568, United States. Electronic address: than927@163.com.
authors.forename: Ting
authors.initials: T
authors.lastname: Han
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, PR China. Electronic address: qinluping@126.com.
authors.forename: Lu-Ping
authors.initials: LP
authors.lastname: Qin
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D003863:Depression / Q000188:drug therapy / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D031701:Piper; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism*; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D010936:Plant Extracts
keywords: Antidepressant; BDNF; CREB-ERK; FST; Piper sarmentosum