ArticlePsychopharmacology2019
Tetramethylpyrazine ameliorates depression by inhibiting TLR4-NLRP3 inflammasome signal pathway in mice.
Article in Psychopharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 74 citations in OpenAlex.
- The NLRP3 inflammasome: pathophysiology and therapeutic implications for schizophrenia and neuropsychiatric disorders.Molecular psychiatry · 2026Review
- Mechanism of Microbiota-Gut-Brain in Perimenopausal Depression: An Inflammatory Perspective.Expert reviews in molecular medicine · 2025Review
- Discovery of Herbal Remedies and Key Components for Major Depressive Disorder Through Biased Random Walk Analysis on a Multiscale Network.International journal of molecular sciences · 2025Article
- Xiangshao Granules Ameliorate Post-stroke Depression by Inhibiting Activation of Microglia and IDO1 Expression in Hippocampus and Prefrontal Cortex.Chinese journal of integrative medicine · 2025Article
- From a traditional medicine monomer to a modern neurotherapeutic scaffold: a review of SAR-Driven tetramethylpyrazine derivatives for cerebrovascular and cognitive health.Frontiers in pharmacology · 2025Review
- NLRP3 Inflammasome: A New Target for the Treatment of CVD and Depression Comorbidity.Mediators of inflammation · 2025Review
- Review
- Chronic Stress-Induced Neuroinflammation: Relevance of Rodent Models to Human Disease.International journal of molecular sciences · 2024Review
- Berberine ameliorates depression-like behaviors in mice via inhibiting NLRP3 inflammasome-mediated neuroinflammation and preventing neuroplasticity disruption.Journal of neuroinflammation · 2023Article
- Echinacoside exerts antidepressant-like effects through enhancing BDNF-CREB pathway and inhibiting neuroinflammationFrontiers in pharmacology · 2022Article
- Regulatory mechanisms of tetramethylpyrazine on central nervous system diseases: A review.Frontiers in pharmacology · 2022Review
- Microglial Inflammatory-Metabolic Pathways and Their Potential Therapeutic Implication in Major Depressive Disorder.Frontiers in psychiatry · 2022Review
- Chinese Herbal Medicine in the Treatment of Depression in Parkinson's Disease: From Molecules to Systems.Frontiers in pharmacology · 2022Review
- The Role of Neutrophil Extracellular Traps in Lipopolysaccharide-Induced Depression-like Behaviors in Mice.Brain sciences · 2021Article
- Salidroside inhibits NLRP3 inflammasome activation and apoptosis in microglia induced by cerebral ischemia/reperfusion injury by inhibiting the TLR4/NF-κB signaling pathway.Annals of translational medicine · 2021Article
- Protective effects of tetramethylpyrazine on dysfunction of the locus coeruleus in rats exposed to single prolonged stress by anti-ER stress mechanism.Psychopharmacology · 2021Article
- Effects of Toll-like receptor 4 inhibition on spatial memory and cell proliferation in male and female adult and aged mice.Brain, behavior, and immunity · 2021Article
- Glycogen Synthase Kinase-3: A Focal Point for Advancing Pathogenic Inflammation in Depression.Cells · 2021Review
- Immune receptor toll-like receptor 4 contributes to stress-induced affective responses in a sex-specific manner.Brain, behavior, & immunity - health · 2021Article
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Depression is a common but serious mental illness; meanwhile, it is also an inflammatory disorder. Toll-like receptor 4 (TLR4), as the pattern recognition receptor, has been shown to play a vital role in neuroinflammation. The nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome acts as an important signaling molecule downstream of TLR4 and can promote the maturation of inflammatory cytokines, such as interleukin-1β (IL-1β). Tetramethylpyrazine (TMP) is a natural compound with neuroprotective effects but with unknown mechanisms on its antidepressant-like effect. In this study, we hypothesized that TMP ameliorates depression may be through the inhibition of the TLR4-NF-κB-NLRP3 signal pathway. Our results have shown that chronic unpredictable mild stress (CUMS) that induced the decreased sucrose preference and increased immobile time was prominently reversed by TMP and fluoxetine. Additionally, we also found that CUMS induced the upregulation of proinflammatory cytokines; TLR4 and NLRP3-associated proteins were significantly suppressed by TMP in the prefrontal cortex and hippocampus. TMP also exhibited potent antioxidant effects and increased the monoamine levels in the serum and brain, such as increasing the activity of SOD and GSH-Px, and reducing the activity of MDA in the serum, and elevating the 5-HT and NE concentration in the serum and brain. Moreover, treatment with Cli-095 (TLR4 inhibitor) also markedly inhibited CUMS-induced depression-like behaviors. Taken together, our findings suggested that TMP exerted a potential antidepressant-like effect in CUMS mice, and the molecular mechanisms may relate to inhibit the TLR4-NF-κB-NLRP3 signaling pathway in the brain.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.