(+)-catechin attenuates NF-κB activation through regulation of Akt, MAPK, and AMPK signaling pathways in LPS-induced BV-2 microglial cells

Sharifah Salwa Syed Hussein, Muhamad Noor Alfarizal Kamarudin, Habsah Abdul Kadir

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61 Citations (Scopus)

Abstract

(+)-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.

Original languageEnglish
Pages (from-to)927-952
Number of pages26
JournalAmerican Journal Of Chinese Medicine
Volume43
Issue number5
DOIs
Publication statusPublished - 28 Aug 2015
Externally publishedYes

Keywords

  • (+)-Catechin
  • Akt
  • AMPK α1
  • ERK1/2
  • Inflammatory Cytokines
  • LPS
  • NF-κB
  • p38 MAPK

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