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

J Ethnopharmacol. 2017 Mar 6:199:9-19. doi: 10.1016/j.jep.2017.01.037. Epub 2017 Jan 23.

Abstract

Ethnopharmacological relevance: 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.

Materials and 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.

Keywords: Antidepressant; BDNF; CREB-ERK; FST; Piper sarmentosum.

MeSH terms

  • Animals
  • Antidepressive Agents / isolation & purification
  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents / therapeutic use
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Depression / drug therapy
  • Depression / metabolism
  • Dose-Response Relationship, Drug
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / metabolism*
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Piper*
  • Pituitary-Adrenal System / drug effects
  • Pituitary-Adrenal System / metabolism*
  • Plant Components, Aerial
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Antidepressive Agents
  • Brain-Derived Neurotrophic Factor
  • Creb1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • Plant Extracts