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

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-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.

Gαq protein signaling in the bed nucleus of the stria terminalis regulate the lipopolysaccharide-induced despair-like behavior in mice

“…This study was approved by the mice intended for guide cannula implantation into the skull were handled individually once daily for the 4 days before surgery, and then twice daily during the 2 days after recovery from anesthesia until the behavioral tests were performed. LPS was dissolved in sterile endotoxin-free isotonic saline and administered intraperitoneally on the first day at a dose of 1.2 mg/kg which dose is an adequate range for inducing the LPS-induced depressive-like behaviors [16] , [29] , [30] , [31] .…”

Xiaoyao Pills Attenuate Inflammation and Nerve Injury Induced by Lipopolysaccharide in Hippocampal Neurons In Vitro

“…And activation of the inflammatory pathway in the brain reduces neurotrophic support and altered glutamate release/reuptake, as well as oxidative stress, leading to excitotoxicity, consistent with neuropathological findings of depression characteristics [ 27 ]. The proinflammatory cytokines can cause sickness behavior and cellular damage [ 28 , 29 ]. An increase of inflammation can lead to negative emotion, which was also supported by studies that induced inflammation through the injection of LPS.…”

Application of Traditional Chinese Medicines in Postoperative Abdominal Adhesion

“…Honokiol, a biologically active substance derived from the bark of magnolia trees, has been shown to exert significant anti-inflammatory, antioxidative, antitumour and neuroprotective effects [31][32][33]. Agacayak et al [34] found that treatment with 1 mg/kg honokiol for 14 days was effective in prevention of PAA in a rat model.…”