Effects of Ganoderic Acid A on Lipopolysaccharide-induced Proinflammatory Cytokine Release from Primary Mouse Microglia Cultures

Overview

Journal Exp Ther Med

Specialty Pathology

Date 2018 Feb 6

PMID 29399089

Citations 14

Authors

Baojin Chi

Shuqiu Wang

Sheng Bi

Wenbo Qin

Dongmei Wu

Zhenguo Luo

Shiliang Gui

Dongwei Wang

Xingzhong Yin

Fangfang Wang

Affiliations

Soon will be listed here.

Abstract

For several thousand years, (Ling-Zhi in Chinese and Reishi in Japanese) has been widely used as a traditional medication for the prevention and treatment of various diseases in Asia. Its major biologically active components, ganoderic acids (GAs), exhibit significant medicinal value due to their anti-inflammatory effects. Dysregulation of microglial function may cause seizures or promote epileptogenesis through release of proinflammatory cytokines, including interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α. At present, only little information is available on the effects of GAs on microglia-mediated inflammation and/or . The present study aimed to investigate the role of GA-A on microglia-mediated inflammation . In addition, the effect of GA-A on lipopolysaccharide (LPS)-evoked alterations in mitochondrial metabolic activity of microglia was evaluated. The results of the present study demonstrated that GA-A significantly decreased LPS-induced IL-1β, IL-6 and TNF-α release from mouse-derived primary cortical microglial cells in a concentration-dependent manner. GA-A treatment reduced LPS-induced expression of nuclear factor (NF)-κB (p65) and its inhibitor, demonstrating that non-toxic suppression of IL-1β, IL-6 and TNF-α production by GA-A is, at least in part, due to suppression of the NF-κB signaling pathway. In addition, the LPS-induced stimulation of mitochondrial activity of microglial cells was abolished by co-treatment with GA-A. Thus, GA-A treatment may be a potential therapeutic strategy for epilepsy prevention by suppressing microglia-derived proinflammatory mediators.

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References

Liu C, Dunkin D, Lai J, Song Y, Ceballos C, Benkov K . Anti-inflammatory Effects of Ganoderma lucidum Triterpenoid in Human Crohn's Disease Associated with Downregulation of NF-κB Signaling. Inflamm Bowel Dis. 2015; 21(8):1918-25. PMC: 4509964. DOI: 10.1097/MIB.0000000000000439. View

Li X, Han X, Bao J, Liu Y, Ye A, Thakur M . Nicotine increases eclampsia-like seizure threshold and attenuates microglial activity in rat hippocampus through the α7 nicotinic acetylcholine receptor. Brain Res. 2016; 1642:487-496. DOI: 10.1016/j.brainres.2016.04.043. View

Zhang F, Liu J, Shi J . Anti-inflammatory activities of resveratrol in the brain: role of resveratrol in microglial activation. Eur J Pharmacol. 2010; 636(1-3):1-7. DOI: 10.1016/j.ejphar.2010.03.043. View

Galic M, Riazi K, Heida J, Mouihate A, Fournier N, Spencer S . Postnatal inflammation increases seizure susceptibility in adult rats. J Neurosci. 2008; 28(27):6904-13. PMC: 3547980. DOI: 10.1523/JNEUROSCI.1901-08.2008. View

Kiyomoto M, Shinoda M, Honda K, Nakaya Y, Dezawa K, Katagiri A . p38 phosphorylation in medullary microglia mediates ectopic orofacial inflammatory pain in rats. Mol Pain. 2015; 11:48. PMC: 4531532. DOI: 10.1186/s12990-015-0053-y. View

Zhang B, Zou J, Han L, Rensing N, Wong M . Microglial activation during epileptogenesis in a mouse model of tuberous sclerosis complex. Epilepsia. 2016; 57(8):1317-25. PMC: 4972670. DOI: 10.1111/epi.13429. View

Chen H, Wang C, Wei X, Ding X, Ying W . Malate-Aspartate Shuttle Inhibitor Aminooxyacetate Acid Induces Apoptosis and Impairs Energy Metabolism of Both Resting Microglia and LPS-Activated Microglia. Neurochem Res. 2015; 40(6):1311-8. DOI: 10.1007/s11064-015-1589-y. View

Dolga A, Granic I, Blank T, Knaus H, Spiess J, Luiten P . TNF-alpha-mediates neuroprotection against glutamate-induced excitotoxicity via NF-kappaB-dependent up-regulation of K2.2 channels. J Neurochem. 2008; 107(4):1158-67. DOI: 10.1111/j.1471-4159.2008.05701.x. View

Kosonowska E, Janeczko K, Setkowicz Z . Inflammation induced at different developmental stages affects differently the range of microglial reactivity and the course of seizures evoked in the adult rat. Epilepsy Behav. 2015; 49:66-70. DOI: 10.1016/j.yebeh.2015.04.063. View

10.

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

11.

Dambach H, Hinkerohe D, Prochnow N, Stienen M, Moinfar Z, Haase C . Glia and epilepsy: experimental investigation of antiepileptic drugs in an astroglia/microglia co-culture model of inflammation. Epilepsia. 2013; 55(1):184-92. DOI: 10.1111/epi.12473. View

12.

Mecha M, Carrillo-Salinas F, Feliu A, Mestre L, Guaza C . Microglia activation states and cannabinoid system: Therapeutic implications. Pharmacol Ther. 2016; 166:40-55. DOI: 10.1016/j.pharmthera.2016.06.011. View

13.

Dudhgaonkar S, Thyagarajan A, Sliva D . Suppression of the inflammatory response by triterpenes isolated from the mushroom Ganoderma lucidum. Int Immunopharmacol. 2009; 9(11):1272-80. DOI: 10.1016/j.intimp.2009.07.011. View

14.

Vezzani A, Maroso M, Balosso S, Sanchez M, Bartfai T . IL-1 receptor/Toll-like receptor signaling in infection, inflammation, stress and neurodegeneration couples hyperexcitability and seizures. Brain Behav Immun. 2011; 25(7):1281-9. DOI: 10.1016/j.bbi.2011.03.018. View

15.

Pfluger P, Viau C, Coelho V, Berwig N, Staub R, Pereira P . Gamma-decanolactone inhibits iNOS and TNF-alpha production by lipopolysaccharide-activated microglia in N9 cells. Eur J Pharmacol. 2016; 780:38-45. DOI: 10.1016/j.ejphar.2016.03.029. View

16.

Tang W, Liu J, Zhao W, Wei D, Zhong J . Ganoderic acid T from Ganoderma lucidum mycelia induces mitochondria mediated apoptosis in lung cancer cells. Life Sci. 2006; 80(3):205-11. DOI: 10.1016/j.lfs.2006.09.001. View

17.

Rummel C . Inflammatory transcription factors as activation markers and functional readouts in immune-to-brain communication. Brain Behav Immun. 2015; 54:1-14. DOI: 10.1016/j.bbi.2015.09.003. View

18.

Lei H, Yang D, Li Y, Wang L, Zheng M . Association between human cytomegalovirus and onset of epilepsy. Int J Clin Exp Med. 2016; 8(11):20556-64. PMC: 4723818. View

19.

Maroso M, Balosso S, Ravizza T, Liu J, Bianchi M, Vezzani A . Interleukin-1 type 1 receptor/Toll-like receptor signalling in epilepsy: the importance of IL-1beta and high-mobility group box 1. J Intern Med. 2011; 270(4):319-26. DOI: 10.1111/j.1365-2796.2011.02431.x. View

20.

Cattepoel S, Schaub A, Ender M, Gaida A, Kropf A, Guggisberg U . Intravenous immunglobulin binds beta amyloid and modifies its aggregation, neurotoxicity and microglial phagocytosis in vitro. PLoS One. 2013; 8(5):e63162. PMC: 3656042. DOI: 10.1371/journal.pone.0063162. View