Antidepressant-Like Effect and Mechanism of Action of Honokiol on the Mouse Lipopolysaccharide (LPS) Depression Model

Molecules. 2019 May 28;24(11):2035. doi: 10.3390/molecules24112035.


There is growing evidence that neuroinflammation is closely linked to depression. Honokiol, a biologically active substance extracted from Magnolia officinalis, which is widely used in traditional Chinese medicine, has been shown to exert significant anti-inflammatory effects and improve depression-like behavior caused by inflammation. However, the specific mechanism of action of this activity is still unclear. In this study, the lipopolysaccharide (LPS) mouse model was used to study the effect of honokiol on depression-like behavior induced by LPS in mice and its potential mechanism. A single administration of LPS (1 mg/kg, intraperitoneal injection) increased the immobility time in the forced swimming test (FST) and tail suspension test (TST), without affecting autonomous activity. Pretreatment with honokiol (10 mg/kg, oral administration) for 11 consecutive days significantly improved the immobility time of depressed mice in the FST and TST experiments. Moreover, honokiol ameliorated LPS-induced NF-κB activation in the hippocampus and significantly reduced the levels of the pro-inflammatory cytokines; tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interferon γ (IFN-γ). In addition, honokiol inhibited LPS-induced indoleamine 2,3-dioxygenase (IDO) activation and quinolinic acid (a toxic product) increase and reduced the level of free calcium in brain tissue, thereby inhibiting calcium overload. In summary, our results indicate that the anti-depressant-like effects of honokiol are mediated by its anti-inflammatory effects. Honokiol may inhibit the LPS-induced neuroinflammatory response through the NF-κB signaling pathway, reducing the levels of related pro-inflammatory cytokines, and furthermore, this may affect tryptophan metabolism and increase neuroprotective metabolites.

Keywords: IDO; NF-κB; anti-inflammatory; antidepressant effect; honokiol; tryptophan–kynurenine pathway.

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use*
  • Autonomic Nervous System / drug effects
  • Biphenyl Compounds / pharmacology
  • Biphenyl Compounds / therapeutic use*
  • Brain / metabolism
  • Calcium / metabolism
  • Cytokines / blood
  • Depression / drug therapy*
  • Depression / physiopathology
  • Disease Models, Animal
  • Hindlimb Suspension
  • Immobilization
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Inflammation Mediators / blood
  • Kynurenine / metabolism
  • Lignans / pharmacology
  • Lignans / therapeutic use*
  • Lipopolysaccharides
  • Mice, Inbred ICR
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Swimming
  • Tryptophan / metabolism


  • Antidepressive Agents
  • Biphenyl Compounds
  • Cytokines
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Inflammation Mediators
  • Lignans
  • Lipopolysaccharides
  • NF-kappa B
  • RNA, Messenger
  • honokiol
  • Kynurenine
  • Tryptophan
  • Calcium