Zhile Capsule Exerts Antidepressant-Like Effects through Upregulation of the BDNF Signaling Pathway and Neuroprotection

Int J Mol Sci. 2019 Jan 8;20(1):195. doi: 10.3390/ijms20010195.


Major depressive disorder is now becoming a common disease in daily life, and most patients do not have satisfactory treatment outcomes. We herein evaluated the therapeutic effects of Zhile capsule and clarified the molecular mechanism. A rat model of chronic unpredictable mild stress-induced depression was established to assess the antidepressant-like effects of Zhile by using the sucrose preference test, open field test, forced swim test, tail suspension test and HPLC. Systems pharmacology was then performed to unravel the underlying mechanism which was confirmed by western blot, enzyme-linked immunosorbent assay, and qPCR. Zhile alleviated depression-like behaviors by upregulating the cAMP-CREB-BDNF (brain-derived neurotrophic factor) axis to exert neuroprotective effects. It may be beneficial to depressive patients in clinical practice.

Keywords: brain-derived neurotrophic factor; chronic unpredictable mild stress; major depressive disorder; neuroprotection; systems pharmacology.

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use*
  • Apoptosis / drug effects
  • Behavior, Animal / drug effects
  • Biogenic Monoamines / metabolism
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Capsules
  • Chronic Disease
  • Cyclic AMP / metabolism
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Depression / complications
  • Depression / drug therapy*
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Hindlimb Suspension
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • Neuroprotection / drug effects*
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Neurotransmitter Agents / metabolism
  • Rats, Sprague-Dawley
  • Signal Transduction* / drug effects
  • Stress, Psychological / complications
  • Stress, Psychological / drug therapy
  • Up-Regulation*


  • Antidepressive Agents
  • Biogenic Monoamines
  • Brain-Derived Neurotrophic Factor
  • Capsules
  • Cyclic AMP Response Element-Binding Protein
  • Drugs, Chinese Herbal
  • Neuroprotective Agents
  • Neurotransmitter Agents
  • Cyclic AMP