ReferenceID 1208
Arctigenin protects against depression by inhibiting microglial activation and neuroinflammation via HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB pathways
Br J Pharmacol
BACKGROUND AND PURPOSE: Arctigenin, a major bioactive component of Fructus arctii, has been reported to have antidepressant-like effects. However, the mechanisms underlying these effects are still unclear. Neuroinflammat
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- Reference Id
- 1208
- Evidence Id
- 17798
- Core Evidence Id
- 17798
- Source Reference Id
- 2404
- Herb2 Reference Id
- HBREF003201
- Subject Paper Key
- HBIN016609_32964428
- Pubmed Id
- 32964428
- Doi
- 10.1111/bph.15261
- Paper Title
- Arctigenin protects against depression by inhibiting microglial activation and neuroinflammation via HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB pathways
- Paper Abstract
- BACKGROUND AND PURPOSE: Arctigenin, a major bioactive component of Fructus arctii, has been reported to have antidepressant-like effects. However, the mechanisms underlying these effects are still unclear. Neuroinflammation can be caused by excessive production of proinflammatory cytokines in microglia via high-mobility group box 1 (HMGB1)/TLR4/NF-kappaB and TNF-alpha/TNFR1/NF-kappaB signalling pathways, leading to depression. In this study, we have investigated the antidepressant mechanism of arctigenin by conducting in vitro and in vivo studies. EXPERIMENTAL APPROACH: The effects of chronic unpredictable mild stress (CUMS) on wild-type (WT) and TLR4-/- mice were examined. Antidepressant-like effects of arctigenin were tested using the CUMS-induced model of depression in WT mice. The effects of arctigenin were assessed on the HMGB1/TLR4/NF-kappaB and TNF-alpha/TNFR1/NF-kappaB signalling pathways in the prefrontal cortex (PFC) of mouse brain and HMGB1- or TNF-alpha-stimulated primary cultured microglia. The interaction between HMGB1 and TLR4 or TNF-alpha and TNFR1 with or without arctigenin was examined by localized surface plasmon resonance (LSPR) and co-immunoprecipitation assays. KEY RESULTS: The immobility times in the tail suspension test (TST) and forced swimming test (FST) were reduced in TLR4-/- mice, compared with WT mice. Arctigenin exhibited antidepressant-like effects. Arctigenin also inhibited microglia activation and inflammatory responses in the PFC of mouse brain. Arctigenin inhibited HMGB1 and TLR4 or TNF-alpha and TNFR1 interactions, and suppressed both HMGB1/TLR4/NF-kappaB and TNF-alpha/TNFR1/NF-kappaB signalling pathways. CONCLUSIONS AND IMPLICATIONS: Arctigenin has antidepressant-like effects by attenuating excessive microglial activation and neuroinflammation through the HMGB1/TLR4/NF-kappaB and TNF-alpha/TNFR1/NF-kappaB signalling pathways. This suggests that arctigenin has potential as a new drug candidate suitable for clinical trials to treat depression.
- Journal
- Br J Pharmacol
- Publish Year
- 2020
- Experiment Subject
- mouse; tnf-alpha-stimulated primary cultured microglia
- Experiment Type
- Animal Experiment
- Phenotype Related
- Neuroinflammation
- Paper Title Cn
- Paper Title En
- Arctigenin protects against depression by inhibiting microglial activation and neuroinflammation via HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB pathways
- Bilingual Status
- semi_complete