RT info:eu-repo/semantics/article
T1 Natural triterpenes modulate immune-inflammatory markers of experimental autoimmune encephalomyelitis: therapeutic implications for multiple sclerosis
A1 Martín Martín, Rubén
A1 Hernández Garrido, Marita
A1 Córdova, Claudia
A1 Nieto Callejo, María Luisa
K1 Encephalomyelitis
K1 Encefalomielitis
K1 Neuroimmunology
K1 Neuroinmunología
K1 Microglia
K1 Microglía
K1 Triterpenes
K1 Triterpenos
K1 3209 Farmacología
AB 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 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.
PB The British Pharmacological Society
SN 1476-5381
YR 2012
FD 2012
LK https://uvadoc.uva.es/handle/10324/46974
UL https://uvadoc.uva.es/handle/10324/46974
LA eng
NO British Journal of Pharmacology, 2012, vol. 166, n. 5. p. 1708-1723
NO Producción Científica
DS UVaDOC
RD 24-nov-2024