TY - JOUR
T1 - (+)-catechin attenuates NF-κB activation through regulation of Akt, MAPK, and AMPK signaling pathways in LPS-induced BV-2 microglial cells
AU - Hussein, Sharifah Salwa Syed
AU - Kamarudin, Muhamad Noor Alfarizal
AU - Kadir, Habsah Abdul
N1 - Funding Information:
This research is supported by High Impact Research Chancellory Grant UM.C/625/1/ HIR/175 from the University of Malaya, MoE Fundamental Research Grant Scheme (MO001-2014) and University of Malaya Postgraduate Research Fund (PG11820-2013A).
Publisher Copyright:
© 2015 World Scientific Publishing Company & Institute for Advanced Research in Asian Science and Medicine.
Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2015/8/28
Y1 - 2015/8/28
N2 - (+)-catechin is a flavanol that possesses various health and medicinal values, which include neuroprotection, anti-oxidation, antitumor and antihepatitis activities. This study investigated the modulatory effects of (+)-catechin on the lipopolysaccharides (LPS)-stimulated BV-2 cells. (+)-catechin attenuated LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and inhibited microglial NO and ROS production. Additionally, (+)-catechin suppressed the production of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, while augmenting IL-4. (+)-catechin attenuated LPS-induced nuclear factor-κB (NF-κB) p65 nuclear translocation via the inhibition of IκB-α phosphorylation. Moreover, (+)-catechin blocked the activation of Akt and its inhibition was shown to play a crucial role in LPS-induced inflammation in BV-2 microglial cells. (+)-catechin also attenuated the LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK1/2), and p-38 mitogen activated protein kinases (p38 MAPK) and specific inhibitors of ERK1/2 (UO126) and p38 MAPK (SB202190) subsequently down-regulated the expression of the proinflammatory mediators iNOS and COX-2. Further mechanistic study revealed that (+)-catechin acted through the amelioration of the LPS-induced suppression of adenosine monophosphate-activated protein kinase (AMPK) activity. Taken together, our data indicate that (+)-catechin exhibits anti-inflammatory effects in BV-2 cells by suppressing the production of proinflammatory mediators and mitigation of NF-κB through Akt, ERK, p38 MAPK, and AMPK pathways.
AB - (+)-catechin is a flavanol that possesses various health and medicinal values, which include neuroprotection, anti-oxidation, antitumor and antihepatitis activities. This study investigated the modulatory effects of (+)-catechin on the lipopolysaccharides (LPS)-stimulated BV-2 cells. (+)-catechin attenuated LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and inhibited microglial NO and ROS production. Additionally, (+)-catechin suppressed the production of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, while augmenting IL-4. (+)-catechin attenuated LPS-induced nuclear factor-κB (NF-κB) p65 nuclear translocation via the inhibition of IκB-α phosphorylation. Moreover, (+)-catechin blocked the activation of Akt and its inhibition was shown to play a crucial role in LPS-induced inflammation in BV-2 microglial cells. (+)-catechin also attenuated the LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK1/2), and p-38 mitogen activated protein kinases (p38 MAPK) and specific inhibitors of ERK1/2 (UO126) and p38 MAPK (SB202190) subsequently down-regulated the expression of the proinflammatory mediators iNOS and COX-2. Further mechanistic study revealed that (+)-catechin acted through the amelioration of the LPS-induced suppression of adenosine monophosphate-activated protein kinase (AMPK) activity. Taken together, our data indicate that (+)-catechin exhibits anti-inflammatory effects in BV-2 cells by suppressing the production of proinflammatory mediators and mitigation of NF-κB through Akt, ERK, p38 MAPK, and AMPK pathways.
KW - (+)-Catechin
KW - Akt
KW - AMPK α1
KW - ERK1/2
KW - Inflammatory Cytokines
KW - LPS
KW - NF-κB
KW - p38 MAPK
UR - http://www.scopus.com/inward/record.url?scp=84940395852&partnerID=8YFLogxK
U2 - 10.1142/S0192415X15500548
DO - 10.1142/S0192415X15500548
M3 - Article
C2 - 26227399
AN - SCOPUS:84940395852
SN - 0192-415X
VL - 43
SP - 927
EP - 952
JO - American Journal Of Chinese Medicine
JF - American Journal Of Chinese Medicine
IS - 5
ER -