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Antidepressant-Like Effect and Mechanism of Action of Honokiol on the Mouse Lipopolysaccharide (LPS) Depression Model
- Source :
- Molecules, Vol 24, Iss 11, p 2035 (2019), Molecules, Volume 24, Issue 11
- Publication Year :
- 2019
- Publisher :
- MDPI AG, 2019.
-
Abstract
- 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-&kappa<br />B activation in the hippocampus and significantly reduced the levels of the pro-inflammatory cytokines<br />tumor necrosis factor &alpha<br />(TNF-&alpha<br />), interleukin 1&beta<br />(IL-1&beta<br />), and interferon &gamma<br />(IFN-&gamma<br />). 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-&kappa<br />B signaling pathway, reducing the levels of related pro-inflammatory cytokines, and furthermore, this may affect tryptophan metabolism and increase neuroprotective metabolites.
- Subjects :
- Lipopolysaccharides
Honokiol
Pharmaceutical Science
Pharmacology
honokiol
NF-κB
Analytical Chemistry
IDO
chemistry.chemical_compound
0302 clinical medicine
Drug Discovery
Kynurenine
anti-inflammatory
Mice, Inbred ICR
0303 health sciences
biology
Depression
NF-kappa B
Tryptophan
Brain
Antidepressive Agents
Hindlimb Suspension
Chemistry (miscellaneous)
Cytokines
Molecular Medicine
Inflammation Mediators
medicine.symptom
medicine.drug_class
antidepressant effect
Autonomic Nervous System
Article
Lignans
Anti-inflammatory
lcsh:QD241-441
Immobilization
03 medical and health sciences
lcsh:Organic chemistry
medicine
Animals
Indoleamine-Pyrrole 2,3,-Dioxygenase
RNA, Messenger
Physical and Theoretical Chemistry
Swimming
Neuroinflammation
030304 developmental biology
tryptophan–kynurenine pathway
Biphenyl Compounds
Organic Chemistry
biology.organism_classification
Tail suspension test
Disease Models, Animal
Magnolia officinalis
chemistry
Mechanism of action
Calcium
030217 neurology & neurosurgery
Quinolinic acid
Behavioural despair test
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Volume :
- 24
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Molecules
- Accession number :
- edsair.doi.dedup.....2ec2d710f9d964bb0f126d22d28f4e06