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Published in: Journal of Neuroinflammation 1/2011

Open Access 01-12-2011 | Short report

Methyl salicylate 2-O-β- D -lactoside, a novel salicylic acid analogue, acts as an anti-inflammatory agent on microglia and astrocytes

Authors: Xi Lan, Rui Liu, Lan Sun, Tiantai Zhang, Guanhua Du

Published in: Journal of Neuroinflammation | Issue 1/2011

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Abstract

Background

Neuroinflammation has been known to play a critical role in the pathogenesis of Alzheimer's disease (AD). Activation of microglia and astrocytes is a characteristic of brain inflammation. Epidemiological studies have shown that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) delays the onset of AD and suppresses its progression. Methyl salicylate-2-O-β-D-lactoside (DL0309) is a new molecule chemically related to salicylic acid. The present study aimed to evaluate the anti-inflammatory effects of DL0309.

Findings

Our studies show that DL0309 significantly inhibits lipopolysaccharide (LPS)-induced release of the pro-inflammatory cytokines IL-6, IL-1β, and TNF-α; and the expression of the inflammation-related proteins iNOS, COX-1, and COX-2 by microglia and astrocytes. At a concentration of 10 μM, DL0309 prominently inhibited LPS-induced activation of NF-κB in glial cells by blocking phosphorylation of IKK and p65, and by blocking IκB degradation.

Conclusions

We demonstrate here for the first time that DL0309 exerts anti-inflammatory effects in glial cells by suppressing different pro-inflammatory cytokines and iNOS/NO. Furthermore, it also regulates the NF-κB signaling pathway by blocking IKK and p65 activation and IκB degradation. DL0309 also acts as a non-selective COX inhibitor in glial cells. These studies suggest that DL0309 may be effective in the treatment of neuroinflammatory disorders, including AD.
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Literature
1.
go back to reference Maragakis NJ, Rothstein JD: Mechanisms of Disease: astrocytes in neurodegenerative disease. Nat Clin Pract Neurol. 2006, 2: 679-689.CrossRefPubMed Maragakis NJ, Rothstein JD: Mechanisms of Disease: astrocytes in neurodegenerative disease. Nat Clin Pract Neurol. 2006, 2: 679-689.CrossRefPubMed
2.
go back to reference Wyss-Coray T, Loike JD, Brionne TC, Lu E, Anankov R, Yan F, Silverstein SC, Husemann J: Adult mouse astrocytes degrade amyloid-beta in vitro and in situ. Nat Med. 2003, 9: 453-457. 10.1038/nm838.CrossRefPubMed Wyss-Coray T, Loike JD, Brionne TC, Lu E, Anankov R, Yan F, Silverstein SC, Husemann J: Adult mouse astrocytes degrade amyloid-beta in vitro and in situ. Nat Med. 2003, 9: 453-457. 10.1038/nm838.CrossRefPubMed
3.
go back to reference Wyss-Coray T: Inflammation in Alzheimer disease: driving force, bystander or beneficial response?. Nat Med. 2006, 12: 1005-1015.PubMed Wyss-Coray T: Inflammation in Alzheimer disease: driving force, bystander or beneficial response?. Nat Med. 2006, 12: 1005-1015.PubMed
4.
go back to reference Benveniste EN: Cytokines: influence on glial cell gene expression and function. Chem Immunol. 1997, 69: 31-75.CrossRefPubMed Benveniste EN: Cytokines: influence on glial cell gene expression and function. Chem Immunol. 1997, 69: 31-75.CrossRefPubMed
5.
go back to reference Streit WJ, Sammons NW, Kuhns AJ, Sparks DL: Dystrophic microglia in the aging human brain. Glia. 2004, 45: 208-212. 10.1002/glia.10319.CrossRefPubMed Streit WJ, Sammons NW, Kuhns AJ, Sparks DL: Dystrophic microglia in the aging human brain. Glia. 2004, 45: 208-212. 10.1002/glia.10319.CrossRefPubMed
6.
go back to reference Allaman I, Belanger M, Magistretti PJ: Astrocyte-neuron metabolic relationships: for better and for worse. Trends Neurosci. 2011, 34: 76-87. 10.1016/j.tins.2010.12.001.CrossRefPubMed Allaman I, Belanger M, Magistretti PJ: Astrocyte-neuron metabolic relationships: for better and for worse. Trends Neurosci. 2011, 34: 76-87. 10.1016/j.tins.2010.12.001.CrossRefPubMed
7.
go back to reference Pinnen F, Sozio P, Cacciatore I, Cornacchia C, Mollica A, Iannitelli DAE, Cataldi A, Zara S, Nasuti C, Di Stefano A: Ibuprofen and Glutathione Conjugate as a Potential Therapeutic Agent for Treating Alzheimer's Disease. Arch Pharm (Weinheim). 2010 Pinnen F, Sozio P, Cacciatore I, Cornacchia C, Mollica A, Iannitelli DAE, Cataldi A, Zara S, Nasuti C, Di Stefano A: Ibuprofen and Glutathione Conjugate as a Potential Therapeutic Agent for Treating Alzheimer's Disease. Arch Pharm (Weinheim). 2010
8.
go back to reference Ray B, Lahiri DK: Neuroinflammation in Alzheimer's disease: different molecular targets and potential therapeutic agents including curcumin. Curr Opin Pharmacol. 2009, 9: 434-444. 10.1016/j.coph.2009.06.012.CrossRefPubMed Ray B, Lahiri DK: Neuroinflammation in Alzheimer's disease: different molecular targets and potential therapeutic agents including curcumin. Curr Opin Pharmacol. 2009, 9: 434-444. 10.1016/j.coph.2009.06.012.CrossRefPubMed
9.
go back to reference Zhang D, Liu R, Sun L, Huang C, Wang C, Zhang DM, Zhang TT, Du GH: Anti-inflammatory activity of methyl salicylate glycosides isolated from Gaultheria yunnanensis (Franch.) Rehder. Molecules. 2011, 16: 3875-3884. 10.3390/molecules16053875.CrossRefPubMed Zhang D, Liu R, Sun L, Huang C, Wang C, Zhang DM, Zhang TT, Du GH: Anti-inflammatory activity of methyl salicylate glycosides isolated from Gaultheria yunnanensis (Franch.) Rehder. Molecules. 2011, 16: 3875-3884. 10.3390/molecules16053875.CrossRefPubMed
10.
go back to reference Zhang B, He XL, Ding Y, Du GH: Gaultherin, a natural salicylate derivative from Gaultheria yunnanensis: towards a better non-steroidal anti-inflammatory drug. Eur J Pharmacol. 2006, 530: 166-171. 10.1016/j.ejphar.2005.11.030.CrossRefPubMed Zhang B, He XL, Ding Y, Du GH: Gaultherin, a natural salicylate derivative from Gaultheria yunnanensis: towards a better non-steroidal anti-inflammatory drug. Eur J Pharmacol. 2006, 530: 166-171. 10.1016/j.ejphar.2005.11.030.CrossRefPubMed
11.
go back to reference McCarthy KD, de Vellis J: Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue. J Cell Biol. 1980, 85: 890-902. 10.1083/jcb.85.3.890.CrossRefPubMed McCarthy KD, de Vellis J: Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue. J Cell Biol. 1980, 85: 890-902. 10.1083/jcb.85.3.890.CrossRefPubMed
12.
go back to reference Drew PD, Chavis JA: The cyclopentone prostaglandin 15-deoxy-Delta(12,14) prostaglandin J2 represses nitric oxide, TNF-alpha, and IL-12 production by microglial cells. J Neuroimmunol. 2001, 115: 28-35. 10.1016/S0165-5728(01)00267-3.CrossRefPubMed Drew PD, Chavis JA: The cyclopentone prostaglandin 15-deoxy-Delta(12,14) prostaglandin J2 represses nitric oxide, TNF-alpha, and IL-12 production by microglial cells. J Neuroimmunol. 2001, 115: 28-35. 10.1016/S0165-5728(01)00267-3.CrossRefPubMed
13.
go back to reference Fiebich BL, Lieb K, Kammerer N, Hull M: Synergistic inhibitory effect of ascorbic acid and acetylsalicylic acid on prostaglandin E2 release in primary rat microglia. J Neurochem. 2003, 86: 173-178.CrossRefPubMed Fiebich BL, Lieb K, Kammerer N, Hull M: Synergistic inhibitory effect of ascorbic acid and acetylsalicylic acid on prostaglandin E2 release in primary rat microglia. J Neurochem. 2003, 86: 173-178.CrossRefPubMed
14.
go back to reference Candelario-Jalil E, de Oliveira AC, Graf S, Bhatia HS, Hull M, Munoz E, Fiebich BL: Resveratrol potently reduces prostaglandin E2 production and free radical formation in lipopolysaccharide-activated primary rat microglia. J Neuroinflammation. 2007, 4: 25-10.1186/1742-2094-4-25.PubMedCentralCrossRefPubMed Candelario-Jalil E, de Oliveira AC, Graf S, Bhatia HS, Hull M, Munoz E, Fiebich BL: Resveratrol potently reduces prostaglandin E2 production and free radical formation in lipopolysaccharide-activated primary rat microglia. J Neuroinflammation. 2007, 4: 25-10.1186/1742-2094-4-25.PubMedCentralCrossRefPubMed
15.
go back to reference Akundi RS, Candelario-Jalil E, Hess S, Hull M, Lieb K, Gebicke-Haerter PJ, Fiebich BL: Signal transduction pathways regulating cyclooxygenase-2 in lipopolysaccharide-activated primary rat microglia. Glia. 2005, 51: 199-208. 10.1002/glia.20198.CrossRefPubMed Akundi RS, Candelario-Jalil E, Hess S, Hull M, Lieb K, Gebicke-Haerter PJ, Fiebich BL: Signal transduction pathways regulating cyclooxygenase-2 in lipopolysaccharide-activated primary rat microglia. Glia. 2005, 51: 199-208. 10.1002/glia.20198.CrossRefPubMed
16.
go back to reference Brambilla R, Bracchi-Ricard V, Hu WH, Frydel B, Bramwell A, Karmally S, Green EJ, Bethea JR: Inhibition of astroglial nuclear factor kappaB reduces inflammation and improves functional recovery after spinal cord injury. J Exp Med. 2005, 202: 145-156. 10.1084/jem.20041918.PubMedCentralCrossRefPubMed Brambilla R, Bracchi-Ricard V, Hu WH, Frydel B, Bramwell A, Karmally S, Green EJ, Bethea JR: Inhibition of astroglial nuclear factor kappaB reduces inflammation and improves functional recovery after spinal cord injury. J Exp Med. 2005, 202: 145-156. 10.1084/jem.20041918.PubMedCentralCrossRefPubMed
17.
go back to reference Thomas T, Nadackal TG, Thomas K: Aspirin and non-steroidal anti-inflammatory drugs inhibit amyloid-beta aggregation. Neuroreport. 2001, 12: 3263-3267. 10.1097/00001756-200110290-00024.CrossRefPubMed Thomas T, Nadackal TG, Thomas K: Aspirin and non-steroidal anti-inflammatory drugs inhibit amyloid-beta aggregation. Neuroreport. 2001, 12: 3263-3267. 10.1097/00001756-200110290-00024.CrossRefPubMed
18.
go back to reference Cornelius C, Fastbom J, Winblad B, Viitanen M: Aspirin, NSAIDs, risk of dementia, and influence of the apolipoprotein E epsilon 4 allele in an elderly population. Neuroepidemiology. 2004, 23: 35-143.CrossRef Cornelius C, Fastbom J, Winblad B, Viitanen M: Aspirin, NSAIDs, risk of dementia, and influence of the apolipoprotein E epsilon 4 allele in an elderly population. Neuroepidemiology. 2004, 23: 35-143.CrossRef
19.
go back to reference Iwata Y, Nicole O, Zurakowski D, Okamura T, Jonas RA: Ibuprofen for neuroprotection after cerebral ischemia. J Thorac Cardiovasc Surg. 2010, 139: 489-493. 10.1016/j.jtcvs.2009.05.049.PubMedCentralCrossRefPubMed Iwata Y, Nicole O, Zurakowski D, Okamura T, Jonas RA: Ibuprofen for neuroprotection after cerebral ischemia. J Thorac Cardiovasc Surg. 2010, 139: 489-493. 10.1016/j.jtcvs.2009.05.049.PubMedCentralCrossRefPubMed
20.
go back to reference Zandi PP, Breitner JC, Anthony JC: Is pharmacological prevention of Alzheimer's a realistic goal?. Expert Opin Pharmacother. 2002, 3: 365-380. 10.1517/14656566.3.4.365.CrossRefPubMed Zandi PP, Breitner JC, Anthony JC: Is pharmacological prevention of Alzheimer's a realistic goal?. Expert Opin Pharmacother. 2002, 3: 365-380. 10.1517/14656566.3.4.365.CrossRefPubMed
21.
go back to reference Ferrera P, Arias C: Differential effects of COX inhibitors against beta-amyloid-induced neurotoxicity in human neuroblastoma cells. Neurochem Int. 2005, 47: 589-596. 10.1016/j.neuint.2005.06.012.CrossRefPubMed Ferrera P, Arias C: Differential effects of COX inhibitors against beta-amyloid-induced neurotoxicity in human neuroblastoma cells. Neurochem Int. 2005, 47: 589-596. 10.1016/j.neuint.2005.06.012.CrossRefPubMed
Metadata
Title
Methyl salicylate 2-O-β- D -lactoside, a novel salicylic acid analogue, acts as an anti-inflammatory agent on microglia and astrocytes
Authors
Xi Lan
Rui Liu
Lan Sun
Tiantai Zhang
Guanhua Du
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2011
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-8-98

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