2024-03-29T05:14:42Zhttps://uvadoc.uva.es/oai/requestoai:uvadoc.uva.es:10324/469742021-06-23T09:53:29Zcom_10324_1134com_10324_931com_10324_894col_10324_1213
2021-06-21T13:17:49Z
urn:hdl:10324/46974
Natural triterpenes modulate immune-inflammatory markers of experimental autoimmune encephalomyelitis: therapeutic implications for multiple sclerosis
Martín Martín, Rubén
Hernández Garrido, Marita
Córdova, Claudia
Nieto Callejo, María Luisa
Producción Científica
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.
2021-06-21T13:17:49Z
2021-06-21T13:17:49Z
2012
info:eu-repo/semantics/article
British Journal of Pharmacology, 2012, vol. 166, n. 5. p. 1708-1723
1476-5381
https://uvadoc.uva.es/handle/10324/46974
10.1111/j.1476-5381.2012.01869.x
eng
https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1476-5381.2012.01869.x
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
© 2012 The British Pharmacological Society
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
The British Pharmacological Society