ArticleJournal of neuroinflammation2015
β-Lapachone suppresses neuroinflammation by modulating the expression of cytokines and matrix metalloproteinases in activated microglia.
Article in Journal of neuroinflammation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 89 citations in OpenAlex.
- Pharmacokinetic and safety evaluation of MB12066, an NQO1 substrate.Drug design, development and therapy · 2017Trial
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- Unraveling the anti-neuroinflammatory mechanisms of Cervus cucumis polypeptide injection in Alzheimer's disease: insights from network pharmacology, molecular docking, molecular dynamics simulation, and experimental validation.Frontiers in aging neuroscience · 2026Article
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- β-Lapachone Exerts Hypnotic Effects via Adenosine ABiomolecules & therapeutics · 2024Article
- NQO1 polymorphism and susceptibility to ischemic stroke in a Chinese population.BMC medical genomics · 2024Article
- An Elusive Target: Inhibitors of JC Polyomavirus Infection and Their Development as Therapeutics for the Treatment of Progressive Multifocal Leukoencephalopathy.International journal of molecular sciences · 2023Review
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- Investigation of DHA-Induced Regulation of Redox Homeostasis in Retinal Pigment Epithelium Cells through the Combination of Metabolic Imaging and Molecular Biology.Antioxidants (Basel, Switzerland) · 2022Article
- Anti-Inflammatory and Neuroprotective Mechanisms of GTS-21, an α7 Nicotinic Acetylcholine Receptor Agonist, in Neuroinflammation and Parkinson's Disease Mouse Models.International journal of molecular sciences · 2022Article
- Menthae Herba Attenuates Neuroinflammation by Regulating CREB/Nrf2/HO-1 Pathway in BV2 Microglial Cells.Antioxidants (Basel, Switzerland) · 2022Article
- The Potent PDE10A Inhibitor MP-10 (PF-2545920) Suppresses Microglial Activation in LPS-Induced Neuroinflammation and MPTP-Induced Parkinson's Disease Mouse Models.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Article
- Cypermethrin Induces the Activation of Rat Primary Microglia and Expression of Inflammatory Proteins.Journal of molecular neuroscience : MN · 2021Article
- Protective effect of recombinantJournal of Zhejiang University. Science. B · 2021Article
- Silencing TAK1 reduces MAPKs-MMP2/9 expression to reduce inflammation-driven neurohistological disruption post spinal cord injury.Cell death discovery · 2021Article
- Losartan improved hippocampal long-term potentiation impairment induced by repeated LPS injection in rats.Physiological reports · 2021Article
- β‑Lapachone ameliorates L‑DOPA‑induced dyskinesia in a 6‑OHDA‑induced mouse model of Parkinson's disease.Molecular medicine reports · 2021Article
- Microglia mediated neuroinflammation - signaling regulation and therapeutic considerations with special reference to some natural compounds.Histology and histopathology · 2020Review
- Effect of doxycycline and meloxicam on cytokines, brain-derived neurotrophic factor, matrix metalloproteinase-3, tissue inhibitor of metalloproteinase-3 and cyclooxygenase-2 in brain.Iranian journal of basic medical sciences · 2020Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundβ-Lapachone (β-LAP) is a natural naphthoquinone compound isolated from the lapacho tree (Tabebuia sp.), and it has been used for treatment of rheumatoid arthritis, infection, and cancer. In the present study, we investigated whether β-LAP has anti-inflammatory effects under in vitro and in vivo neuroinflammatory conditions.
methodsThe effects of β-LAP on the expression of inducible nitric oxide synthase (iNOS), cytokines, and matrix metalloproteinases (MMPs) were examined in lipopolysaccharide (LPS)-stimulated BV2 microglial cells and rat primary microglia by ELISA, reverse transcription polymerase chain reaction (RT-PCR), and Western blot analysis. Microglial activation and the expression levels of proinflammatory molecules were measured in the LPS-injected mouse brain by immunohistochemistry and RT-PCR analysis. The detailed molecular mechanism underlying the anti-inflammatory effects of β-LAP was analyzed by electrophoretic mobility shift assay, reporter gene assay, Western blot, and RT-PCR analysis.
resultsβ-LAP inhibited the expression of iNOS, proinflammatory cytokines, and MMPs (MMP-3, MMP-8, MMP-9) at mRNA and protein levels in LPS-stimulated microglia. On the other hand, β-LAP upregulated the expressions of anti-inflammatory molecules such as IL-10, heme oxygenase-1 (HO-1), and the tissue inhibitor of metalloproteinase-2 (TIMP-2). The anti-inflammatory effect of β-LAP was confirmed in an LPS-induced systemic inflammation mouse model. Thus, β-LAP inhibited microglial activation and the expressions of iNOS, proinflammatory cytokines, and MMPs in the LPS-injected mouse brain. Further mechanistic studies revealed that β-LAP exerts anti-inflammatory effects by inhibiting MAPKs, PI3K/AKT, and NF-κB/AP-1 signaling pathways in LPS-stimulated microglia. β-LAP also inhibited reactive oxygen species (ROS) production by suppressing the expression and/or phosphorylation of NADPH oxidase subunit proteins, such as p47(phox) and gp91(phox). The anti-oxidant effects of β-LAP appeared to be related with the increase of HO-1 and NQO1 via the Nrf2/anti-oxidant response element (ARE) pathway and/or the PKA pathway.
conclusionsThe strong anti-inflammatory/anti-oxidant effects of β-LAP may provide preventive therapeutic potential for various neuroinflammatory disorders.
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