| Natural Triterpenes Modulate Immune-Inflammatory Hallmarks to Protect against Experimental Autoimmune Encephalomyelitis. Therapeutic Implications for Multiple Sclerosis. | |
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MedLine Citation:
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PMID: 22260389 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Background 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 glia activation and CNS tissues destruction. Oleanolic acid and erythrodiol are natural triterpenes that display strong antiinflammatory and immunomodulatory activities. We recently described that oleanolic acid beneficially influences the course of established EAE. We now extend our previous observations to erythrodiol, and also address the efficacy of both molecules, in protecting against neuroinflammatory diseases, when administrated 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. Results. Triterpenes protected against EAE by restricting the infiltration of inflammatory cells into the CNS and by preventing blood-brain barrier disruption. Triterpenes-pretreated EAE-mice exhibited less leptin secretion, and switched cytokine production towards a Th2/regulatory profile: levels of Th1 and Th17 cytokines decreased, while expression of Th2 cytokines was up-regulated in both serum and spinal cord. Triterpenes also affected the humoral response causing auto-antibody production inhibition. In addition, in vitro triterpenes abrogated ERK and rS6 phosphorylation, 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 hallmarks of EAE. We envision these natural products as novel helpful tools for intervention in autoimmune and neurodegenerative diseases including MS. |
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Authors:
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R Martín; M Hernández; Cl Córdova; M L Nieto |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-20 |
Journal Detail:
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Title: British journal of pharmacology Volume: - ISSN: 1476-5381 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society. |
Affiliation:
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Instituto de Biología y Genética Molecular, CSIC-Universidad de Valladolid, Spain. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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