Natural triterpenes modulate immune-inflammatory markers of experimental autoimmune encephalomyelitis: therapeutic implications for multiple sclerosis

Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are inflammatory demyelinating diseases that develop as a result of deregulated immune responses causing glial activation and destruction of CNS tissues. Oleanolic acid and erythrodiol are natural triterpe...

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Authors: Martín, Rubén, Hernández, Marita, Cordova, Claudia, Nieto, María Luisa
Format: article
Status:Versión aceptada para publicación
Publication Date:2012
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/113324
Online Access:http://hdl.handle.net/10261/113324
Access Level:Open access
Keyword:Encephalomyelitis
Neuroimmunology
Inflammation
Microglia
Pharmacology
Triterpenes
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spelling Natural triterpenes modulate immune-inflammatory markers of experimental autoimmune encephalomyelitis: therapeutic implications for multiple sclerosisMartín, RubénHernández, MaritaCordova, ClaudiaNieto, María LuisaEncephalomyelitisNeuroimmunologyInflammationMicrogliaPharmacologyTriterpenesMultiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are inflammatory demyelinating diseases that develop as a result of deregulated immune responses causing glial activation and destruction of CNS tissues. Oleanolic acid and erythrodiol are natural triterpenes that display strong anti-inflammatory and immunomodulatory activities. Oleanolic acid beneficially influences the course of established EAE. We now extend our previous observations to erythrodiol and address the efficacy of both compounds to protect against EAE, given under different regimens.The utility of both triterpenes in disease prevention was evaluated at a clinical and molecular level: in vivo through their prophylactic administration to myelin oligodendrocyte protein-immunized C57BL/6 mice, and in vitro through their addition to stimulated-BV2 microglial cells.These triterpenes protected against EAE by restricting infiltration of inflammatory cells into the CNS and by preventing blood–brain barrier disruption. Triterpene-pretreated EAE-mice exhibited less leptin secretion, and switched cytokine production towards a Th2/regulatory profile, with lower levels of Th1 and Th17 cytokines and higher expression of Th2 cytokines in both serum and spinal cord. Triterpenes also affected the humoral response causing auto-antibody production inhibition. In vitro, triterpenes inhibited ERK and rS6 phosphorylation and reduced the proliferative response, phagocytic properties and synthesis of proinflammatory mediators induced by the addition of inflammatory stimuli to microglia.Both triterpenes restricted the development of the characteristic features of EAE. We envision these natural products as novel helpful tools for intervention in autoimmune and neurodegenerative diseases including MS.This work was supported by grants SAF2009-08407 from the Spanish Ministry of Science and Innovation, and CSI11A08 from the Autonomous Government of Castilla y León.Peer reviewedWiley-BlackwellBritish Pharmacological SocietyMinisterio de Ciencia e Innovación (España)Junta de Castilla y LeónConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201520152012info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/113324reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1111/j.1476-5381.2012.01869.xSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1133242026-05-22T06:33:51Z
dc.title.none.fl_str_mv Natural triterpenes modulate immune-inflammatory markers of experimental autoimmune encephalomyelitis: therapeutic implications for multiple sclerosis
title Natural triterpenes modulate immune-inflammatory markers of experimental autoimmune encephalomyelitis: therapeutic implications for multiple sclerosis
spellingShingle Natural triterpenes modulate immune-inflammatory markers of experimental autoimmune encephalomyelitis: therapeutic implications for multiple sclerosis
Martín, Rubén
Encephalomyelitis
Neuroimmunology
Inflammation
Microglia
Pharmacology
Triterpenes
title_short Natural triterpenes modulate immune-inflammatory markers of experimental autoimmune encephalomyelitis: therapeutic implications for multiple sclerosis
title_full Natural triterpenes modulate immune-inflammatory markers of experimental autoimmune encephalomyelitis: therapeutic implications for multiple sclerosis
title_fullStr Natural triterpenes modulate immune-inflammatory markers of experimental autoimmune encephalomyelitis: therapeutic implications for multiple sclerosis
title_full_unstemmed Natural triterpenes modulate immune-inflammatory markers of experimental autoimmune encephalomyelitis: therapeutic implications for multiple sclerosis
title_sort Natural triterpenes modulate immune-inflammatory markers of experimental autoimmune encephalomyelitis: therapeutic implications for multiple sclerosis
dc.creator.none.fl_str_mv Martín, Rubén
Hernández, Marita
Cordova, Claudia
Nieto, María Luisa
author Martín, Rubén
author_facet Martín, Rubén
Hernández, Marita
Cordova, Claudia
Nieto, María Luisa
author_role author
author2 Hernández, Marita
Cordova, Claudia
Nieto, María Luisa
author2_role author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Junta de Castilla y León
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Encephalomyelitis
Neuroimmunology
Inflammation
Microglia
Pharmacology
Triterpenes
topic Encephalomyelitis
Neuroimmunology
Inflammation
Microglia
Pharmacology
Triterpenes
description Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are inflammatory demyelinating diseases that develop as a result of deregulated immune responses causing glial activation and destruction of CNS tissues. Oleanolic acid and erythrodiol are natural triterpenes that display strong anti-inflammatory and immunomodulatory activities. Oleanolic acid beneficially influences the course of established EAE. We now extend our previous observations to erythrodiol and address the efficacy of both compounds to protect against EAE, given under different regimens.
publishDate 2012
dc.date.none.fl_str_mv 2012
2015
2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/113324
url http://hdl.handle.net/10261/113324
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1111/j.1476-5381.2012.01869.x
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Wiley-Blackwell
British Pharmacological Society
publisher.none.fl_str_mv Wiley-Blackwell
British Pharmacological Society
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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