A New Neolignan Derivative, Balanophonin Isolated from Firmiana simplex Delays the Progress of Neuronal Cell Death by Inhibiting Microglial Activation.
10.4062/biomolther.2016.224
- Author:
Soo Young LIM
1
;
Lalita SUBEDI
;
Dongyun SHIN
;
Chung Sub KIM
;
Kang Ro LEE
;
Sun Yeou KIM
Author Information
1. College of Pharmacy, Gachon University, Incheon 21936, Republic of Korea. sunnykim@gachon.ac.kr
- Publication Type:Original Article
- Keywords:
Firmiana simplex;
Neuroinflammation;
Balanophonin;
Microglia;
Neuroprotection;
Apoptosis
- MeSH:
Apoptosis;
Caspase 3;
Cell Death*;
Cyclooxygenase 2;
Dinoprostone;
JNK Mitogen-Activated Protein Kinases;
Microglia;
Mitogen-Activated Protein Kinases;
Necrosis;
Nerve Degeneration;
Neurodegenerative Diseases;
Neurons*;
Neuroprotection;
Nitric Oxide;
Nitric Oxide Synthase Type II;
p38 Mitogen-Activated Protein Kinases;
Phosphotransferases;
Poly(ADP-ribose) Polymerases
- From:Biomolecules & Therapeutics
2017;25(5):519-527
- CountryRepublic of Korea
- Language:English
-
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-1β (IL-1β), and tumor necrosis factor-α (TNF-α), 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.
