Cited by 101Neuroinflammation and Neurodegeneration MechanismsPain Mechanisms and TreatmentsNeurological Disease Mechanisms and Treatments

Benfotiamine Attenuates Inflammatory Response in LPS Stimulated BV-2 Microglia

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Bozic, Iva, Savic, Danijela, Laketa, Danijela, Bjelobaba, Ivana, Milenkovic, Ivan, Pekovic, Sanja, Nedeljkovic, Nadezda, Lavrnja, Irena·2015·PLOS ONE

Abstract

Microglial cells are resident immune cells of the central nervous system (CNS), recognized as key elements in the regulation of neural homeostasis and the response to injury and repair. As excessive activation of microglia may lead to neurodegeneration, therapeutic strategies targeting its inhibition were shown to improve treatment of most neurodegenerative diseases. Benfotiamine is a synthetic vitamin B1 (thiamine) derivate exerting potentially anti-inflammatory effects. Despite the encouraging results regarding benfotiamine potential to alleviate diabetic microangiopathy, neuropathy and other oxidative stress-induced pathological conditions, its activities and cellular mechanisms during microglial activation have yet to be elucidated. In the present study, the anti-inflammatory effects of benfotiamine were investigated in lipopolysaccharide (LPS)-stimulated murine BV-2 microglia. We determined that benfotiamine remodels activated microglia to acquire the shape that is characteristic of non-stimulated BV-2 cells. In addition, benfotiamine significantly decreased production of pro-inflammatory mediators such as inducible form of nitric oxide synthase (iNOS) and NO; cyclooxygenase-2 (COX-2), heat-shock protein 70 (Hsp70), tumor necrosis factor alpha α (TNF-α), interleukin-6 (IL-6), whereas it increased anti-inflammatory interleukin-10 (IL-10) production in LPS stimulated BV-2 microglia. Moreover, benfotiamine suppressed the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinases (JNK) and protein kinase B Akt/PKB. Treatment with specific inhibitors revealed that benfotiamine-mediated suppression of NO production was via JNK1/2 and Akt pathway, while the cytokine suppression includes ERK1/2, JNK1/2 and Akt pathways. Finally, the potentially protective effect is mediated by the suppression of translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the nucleus. Therefore, benfotiamine may have therapeutic potential for neurodegenerative diseases by inhibiting inflammatory mediators and enhancing anti-inflammatory factor production in activated microglia.

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Authors
Bozic, I., Savic, D., Laketa, D., Bjelobaba, I., Milenkovic, I., Pekovic, S., Nedeljkovic, N., & Lavrnja, I.
Affiliations
University of Belgrade (RS)
Corresponding author
Lavrnja, Irena
Venue
PLOS ONE
Published
2015-02-19
Volume
10
Issue
2
Pages
e0118372
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2090822573
Cited by
101
References
75
Citations by year
2026: 10 · 2025: 7 · 2024: 4 · 2023: 11 · 2022: 6 · 2021: 6 · 2020: 14 · 2019: 12 · 2018: 5 · 2017: 13 · 2016: 8 · 2015: 5
FWCI
5.11
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
  • Digital Repository of Archived Publications (University of Belgrade, Institute for Biological Research Sinisa Stankovic) (submittedVersion)
Funders
Ministarstvo Prosvete, Nauke i Tehnološkog Razvoja (III 41014, 41014)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
benfotiamine, microglial activation, neuroinflammation, lipopolysaccharide, BV-2 cells, anti-inflammatory activity, nitric oxide, inducible nitric oxide synthase, cyclooxygenase-2, TNF-α, interleukin-6, IL-10, ERK signaling, JNK signaling, Akt signaling, NF-κB nuclear translocation, neurodegenerative diseases
MeSH terms
Animals, Anti-Inflammatory Agents, Cell Line, Cell Survival, Cytoskeleton, Lipopolysaccharides, Microscopy, Fluorescence, Nitric Oxide, Thiamine, Blotting, Western, Signal Transduction, Cytokines, Microglia, HSP70 Heat-Shock Proteins, Mitogen-Activated Protein Kinases, Protein Kinase Inhibitors, Proto-Oncogene Proteins c-akt, Mice, Cyclooxygenase 2, Nitric Oxide Synthase Type II

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