Biomolecules & Therapeutics  
A New Neolignan Derivative, Balanophonin Isolated from Firmiana simplex Delays the Progress of Neuronal Cell Death by Inhibiting Microglial Activation
Soo Young Lim1,2,†, Lalita Subedi1,2,†, Dongyun Shin1,2, Chung Sub Kim4, Kang Ro Lee4 and Sun Yeou Kim1,2,3,*
1College of Pharmacy, Gachon University, Incheon 21936,
2Gachon Institute of Pharmaceutical Science, Gachon University, Incheon 21936,
3Gachon Medical Research Institute, Gil Medical Center, Incheon 21565,
4Natural Products Laboratory, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
E-mail: sunnykim@gachon.ac.kr
Tel: +82-32-899-6411, Fax: +82-32-899-8962
The first two authors contributed equally to this work.
Received: September 30, 2016; Revised: January 17, 2017; Accepted: February 20, 2017; Published online: May 30, 2017.
© The Korean Society of Applied Pharmacology. All rights reserved.

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.
Keywords: Firmiana simplex, Neuroinflammation, Balanophonin, Microglia, Neuroprotection, Apoptosis


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