title: Natural triterpenes modulate immune-inflammatory markers of experimental autoimmune encephalomyelitis: therapeutic implications for multiple sclerosis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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
  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
  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.
authors.affiliation: Instituto de Biología y Genética Molecular, CSIC-Universidad de Valladolid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Martín
authors.forename: M
authors.initials: M
authors.lastname: Hernández
authors.forename: C
authors.initials: C
authors.lastname: Córdova
authors.forename: M L
authors.initials: ML
authors.lastname: Nieto
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001812:Blood-Brain Barrier / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000097:blood / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D020738:Leptin / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects; D013116:Spinal Cord / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D006023:Glycoproteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007155:Immunologic Factors; D020738:Leptin; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); C077953:erythrodiol; D009828:Oleanolic Acid