Abstract
Inflammation and oxidative stress have been reported to play critical roles in the pathogenesis of neurodegenerative disease. Forsythiaside A, a phenylethanoside product isolated from air-dried fruits of Forsythia suspensa, has been reported to have anti-inflammatory and antioxidant effects. In this study, the anti-inflammatory effects of forsythiaside A on LPS-stimulated BV2 microglia cells and primary microglia cells were investigated. The production of inflammatory mediators TNF-α, IL-1β, NO and PGE2 were detected in this study. NF-κB, nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) expression were detected by western blot analysis. Our results showed that forsythiaside A significantly inhibited LPS-induced inflammatory mediators TNF-α, IL-1β, NO and PGE2 production. LPS-induced NF-κB activation was suppressed by forsythiaside A. Furthermore, forsythiaside A was found to up-regulate the expression of Nrf2 and HO-1. In conclusion, this study demonstrates that forsythiaside A inhibits LPS-induced inflammatory responses in BV2 microglia cells and primary microglia cells through inhibition of NF-κB activation and activation of Nrf2/HO-1 signaling pathway.
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References
Hirsch EC, Hunot S (2009) Neuroinflammation in Parkinson’s disease: a target for neuroprotection? Lancet Neurol 8:382–397
Mosley RL, Benner EJ, Kadiu I, Thomas M, Boska MD, Hasan K et al (2006) Neuroinflammation, oxidative stress and the pathogenesis of Parkinson’s disease. Clin Neurosci Res 6:261–281
Liu B, Hong JS (2003) Role of microglia in inflammation-mediated neurodegenerative diseases: mechanisms and strategies for therapeutic intervention. J Pharmacol Exp Ther 304:1–7
Park HY, Han MH, Park C, Jin CY, Kim GY, Choi IW et al (2011) Anti-inflammatory effects of fucoidan through inhibition of NF-kappa B, MAPK and Akt activation in lipopolysaccharide-induced BV2 microglia cells. Food Chem Toxicol 49:1745–1752
Zhong LM, Zong Y, Sun L, Guo JZ, Zhang W, He Y et al (2012) Resveratrol inhibits inflammatory responses via the mammalian target of rapamycin signaling pathway in cultured LPS-stimulated microglial cells. Plos One 7:e32195
Yu Z, Tang L, Chen L, Li J, Wu W, Hu C (2015) Capillarisin suppresses lipopolysaccharide-induced inflammatory mediators in BV2 microglial cells by suppressing TLR4-mediated NF-kappaB and MAPKs signaling pathway. Neurochem Res 40:1095–1101
Zhang Y, Chen WA (2015) Biochanin A inhibits lipopolysaccharide-induced inflammatory cytokines and mediators production in BV2 microglia. Neurochem Res 40:165–171
Qu H, Zhang Y, Wang Y, Li B, Sun W (2008) Antioxidant and antibacterial activity of two compounds (forsythiaside and forsythin) isolated from Forsythia suspensa. J Pharm Pharmacol 60:261–266
Kim JM, Kim S, Kim DH, Lee CH, Park SJ, Jung JW et al (2011) Neuroprotective effect of forsythiaside against transient cerebral global ischemia in gerbil. Eur J Pharmacol 660:326–333
Huang C, Lin Y, Su H, Ye D (2015) Forsythiaside protects against hydrogen peroxide-induced oxidative stress and apoptosis in PC12 cell. Neurochem Res 40:27–35
Cheng G, Zhao Y, Li H, Wu Y, Li X, Han Q et al (2014) Forsythiaside attenuates lipopolysaccharide-induced inflammatory responses in the bursa of Fabricius of chickens by downregulating the NF-κB signaling pathway. Exp Ther Med 7:179–184
Pan C-W, Zhou G-Y, Chen W-L, Zhuge L, Jin L-X, Zheng Y et al (2015) Protective effect of forsythiaside A on lipopolysaccharide/d-galactosamine-induced liver injury. Int Immunopharmacol 26:80–85
Zhou L, Yang H, Ai Y, Xie Y, Fu Y (2014) Protective effect of forsythiaside A on acute lung injure induced by lipopolysaccharide in mice. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 30:151–154
Park J, Min JS, Kim B, Chae UB, Yun JW, Choi MS et al (2015) Mitochondrial ROS govern the LPS-induced pro-inflammatory response in microglia cells by regulating MAPK and NF-kappaB pathways. Neurosci Lett 584:191–196
Monji A, Kato TA, Mizoguchi Y, Horikawa H, Seki Y, Kasai M et al (2013) Neuroinflammation in schizophrenia especially focused on the role of microglia. Prog Neuropsychopharmacol Biol Psychiatry 42:115–121
Scheld WM, Koedel U, Nathan B, Pfister H-W (2002) Pathophysiology of bacterial meningitis: mechanism (s) of neuronal injury. J Infect Dis 186:S225–S233
Qin L, Li G, Qian X, Liu Y, Wu X, Liu B et al (2005) Interactive role of the toll-like receptor 4 and reactive oxygen species in LPS-induced microglia activation. Glia 52:78–84
Wang AL, Albert C, Lau LT, Lee C, Tso MO (2005) Minocycline inhibits LPS-induced retinal microglia activation. Neurochem Int 47:152–158
Im NK, Zhou W, Na M, Jeong GS (2015) Pierisformoside B exhibits neuroprotective and anti-inflammatory effects in murine hippocampal and microglial cells via the HO-1/Nrf2-mediated pathway. Int Immunopharmacol 24:353–360
Munoz L, Ammit AJ (2010) Targeting p38 MAPK pathway for the treatment of Alzheimer’s disease. Neuropharmacology 58:561–568
Wang CX, Shuaib A (2002) Involvement of inflammatory cytokines in central nervous system injury. Prog Neurobiol 67:161–172
Shakibaei M, John T, Seifarth C, Mobasheri A (2007) Resveratrol inhibits IL-1β-induced stimulation of caspase-3 and cleavage of PARP in human articular chondrocytes in vitro. Ann N Y Acad Sci 1095:554–563
Sanz-Rosa D, Oubina MP, Cediel E, de las Heras N, Vegazo O, Jimenez J et al (2005) Effect of AT1 receptor antagonism on vascular and circulating inflammatory mediators in SHR: role of NF-κB/IκB system. Am J Physiol Heart Circ Physiol 288:H111–H115
Lee I-S, Lim J, Gal J, Kang JC, Kim HJ, Kang BY et al (2011) Anti-inflammatory activity of xanthohumol involves heme oxygenase-1 induction via NRF2-ARE signaling in microglial BV2 cells. Neurochem Int 58:153–160
Lee S, Suk K (2007) Heme oxygenase-1 mediates cytoprotective effects of immunostimulation in microglia. Biochem Pharmacol 74:723–729
Li WG, Khor TO, Xu CJ, Shen GX, Jeong WS, Yu S et al (2008) Activation of Nrf2-antioxidant signaling attenuates NF kappa B-inflammatory response and elicits apoptosis. Biochem Pharmacol 76:1485–1489
Ishii T, Itoh K, Takahashi S, Sato H, Yanagawa T, Katoh Y et al (2000) Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages. J Biol Chem 275:16023–16029
Acknowledgments
This study was supported by Grants from the ‘Neuroprotective effects of microRNA-124 on dopaminergic neurons in Parkinson’s disease and its related mechanism (81371397)’ and The Guangdong Provincial Clinical Medical Centre for Neurosurgery (No. 2013B0204000 05).
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Wang, Y., Zhao, H., Lin, C. et al. Forsythiaside A Exhibits Anti-inflammatory Effects in LPS-Stimulated BV2 Microglia Cells Through Activation of Nrf2/HO-1 Signaling Pathway. Neurochem Res 41, 659–665 (2016). https://doi.org/10.1007/s11064-015-1731-x
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DOI: https://doi.org/10.1007/s11064-015-1731-x