Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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A New Neolignan Derivative, Balanophonin Isolated from Firmiana simplex Delays the Progress of Neuronal Cell Death by Inhibiting Microglial Activation

  • Lim, Soo Young (College of Pharmacy, Gachon University) ;
  • Subedi, Lalita (College of Pharmacy, Gachon University) ;
  • Shin, Dongyun (College of Pharmacy, Gachon University) ;
  • Kim, Chung Sub (Natural Products Laboratory, School of Pharmacy, Sungkyunkwan University) ;
  • Lee, Kang Ro (Natural Products Laboratory, School of Pharmacy, Sungkyunkwan University) ;
  • Kim, Sun Yeou (College of Pharmacy, Gachon University)
  • Received : 2016.09.30
  • Accepted : 2017.02.20
  • Published : 2017.09.01
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Abstract

Excessive activation of microglia causes the continuous production of neurotoxic mediators, which further causes neuron degeneration. Therefore, inhibition of microglial activation is a possible target for the treatment of neurodegenerative disorders. Balanophonin, a natural neolignoid from Firmiana simplex, has been reported to have anti-inflammatory and anti-cancer effects. In this study, we aimed to evaluate the anti-neuroinflammatory effects and mechanism of balanophonin in lipopolysaccharide (LPS)-stimulated BV2 microglia cells. BV2 microglia cells were stimulated with LPS in the presence or absence of balanophonin. The results indicated that balanophonin reduced not only the LPS-mediated TLR4 activation but also the production of inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), $Interleukin-1{\beta}$ ($IL-1{\beta}$), and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), in BV2 cells. Balanophonin also inhibited LPS-induced inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX2) protein expression and mitogen activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 MAPK. Interestingly, it also inhibited neuronal cell death resulting from LPS-activated microglia by regulating cleaved caspase-3 and poly ADP ribose polymerase (PARP) cleavage in N2a cells. In conclusion, our data indicated that balanophonin may delay the progression of neuronal cell death by inhibiting microglial activation.

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References

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