TY  - JOUR
AU  - Božić, Iva
AU  - Savić, Danijela
AU  - Laketa, Danijela
AU  - Bjelobaba, Ivana
AU  - Milenkovic, Ivan
AU  - Peković, Sanja
AU  - Nedeljkovic, Nadezda
AU  - Lavrnja, Irena
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2001
AB  - 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 a (TNF-alpha), 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-kappa B) 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.
T2  - Plos One
T1  - Benfotiamine Attenuates Inflammatory Response in LPS Stimulated BV-2
 Microglia
IS  - e0118372
VL  - 10
DO  - 10.1371/journal.pone.0118372
ER  - 

@article{
author = "Božić, Iva and Savić, Danijela and Laketa, Danijela and Bjelobaba, Ivana and Milenkovic, Ivan and Peković, Sanja and Nedeljkovic, Nadezda and Lavrnja, Irena",
year = "2015",
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 a (TNF-alpha), 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-kappa B) 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.",
journal = "Plos One",
title = "Benfotiamine Attenuates Inflammatory Response in LPS Stimulated BV-2
 Microglia",
number = "e0118372",
volume = "10",
doi = "10.1371/journal.pone.0118372"
}

Božić, I., Savić, D., Laketa, D., Bjelobaba, I., Milenkovic, I., Peković, S., Nedeljkovic, N.,& Lavrnja, I.. (2015). Benfotiamine Attenuates Inflammatory Response in LPS Stimulated BV-2
 Microglia. in Plos One, 10(e0118372).
https://doi.org/10.1371/journal.pone.0118372

Božić I, Savić D, Laketa D, Bjelobaba I, Milenkovic I, Peković S, Nedeljkovic N, Lavrnja I. Benfotiamine Attenuates Inflammatory Response in LPS Stimulated BV-2
 Microglia. in Plos One. 2015;10(e0118372).
doi:10.1371/journal.pone.0118372 .

Božić, Iva, Savić, Danijela, Laketa, Danijela, Bjelobaba, Ivana, Milenkovic, Ivan, Peković, Sanja, Nedeljkovic, Nadezda, Lavrnja, Irena, "Benfotiamine Attenuates Inflammatory Response in LPS Stimulated BV-2
 Microglia" in Plos One, 10, no. e0118372 (2015),
https://doi.org/10.1371/journal.pone.0118372 . .