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dc.contributor.authorMartín Martín, Rubén
dc.contributor.authorHernández Garrido, Marita 
dc.contributor.authorCórdova, Claudia
dc.contributor.authorNieto Callejo, María Luisa
dc.date.accessioned2021-06-21T13:17:49Z
dc.date.available2021-06-21T13:17:49Z
dc.date.issued2012
dc.identifier.citationBritish Journal of Pharmacology, 2012, vol. 166, n. 5. p. 1708-1723es
dc.identifier.issn1476-5381es
dc.identifier.urihttps://uvadoc.uva.es/handle/10324/46974
dc.descriptionProducción Científicaes
dc.description.abstractBackground and purpose: 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. Experimental approach: 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. Key results: 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. Conclusions and implications: 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.es
dc.format.mimetypeapplication/pdfes
dc.language.isoenges
dc.publisherThe British Pharmacological Societyes
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subject.classificationEncephalomyelitises
dc.subject.classificationEncefalomielitises
dc.subject.classificationNeuroimmunologyes
dc.subject.classificationNeuroinmunologíaes
dc.subject.classificationMicrogliaes
dc.subject.classificationMicroglíaes
dc.subject.classificationTriterpeneses
dc.subject.classificationTriterpenoses
dc.titleNatural triterpenes modulate immune-inflammatory markers of experimental autoimmune encephalomyelitis: therapeutic implications for multiple sclerosises
dc.typeinfo:eu-repo/semantics/articlees
dc.rights.holder© 2012 The British Pharmacological Societyes
dc.identifier.doi10.1111/j.1476-5381.2012.01869.xes
dc.relation.publisherversionhttps://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1476-5381.2012.01869.xes
dc.peerreviewedSIes
dc.description.projectMinisterio de Ciencia e Innovación (grant SAF2009-08407)es
dc.description.projectJunta de Castilla y León (grant CSI11A08)es
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersiones
dc.subject.unesco3209 Farmacologíaes


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