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J Nutr Biochem ; 55: 219-228, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29567576

RESUMO

Human natural killer-1 (HNK-1) cell antigen is a glycan epitope involved in several neural events, such as neuritogenesis, myelination, synaptic plasticity and regeneration of the nervous system after injury. We have recently identified the small organic compound ursolic acid (UA) as a HNK-1 mimetic with the aim to test its therapeutic potential in the central nervous system. UA, a plant-derived pentacyclic triterpenoid, is well known for its multiple biological functions, including neuroprotective, antioxidant and anti-inflammatory activities. In the present study, we evaluated its functions in a mouse model of spinal cord injury (SCI) and explored the molecular mechanisms underlying its positive effects. Oral administration of UA to mice 1 h after SCI and thereafter once daily for 6 weeks enhanced the regaining of motor functions and axonal regrowth, and decreased astrogliosis. UA administration decreased levels of proinflammatory markers, including interleukin-6 and tumor necrosis factor-α, in the injured spinal cord at the acute phase of inflammation and activated the mitogen-activated protein kinase and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways in the injured spinal cord. Taken together, these results suggest that UA may be a candidate for treatment of nervous system injuries.


Assuntos
Antígenos CD57/química , Traumatismos da Medula Espinal/tratamento farmacológico , Triterpenos/farmacologia , Animais , Axônios/efeitos dos fármacos , Citocinas/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Filamentos Intermediários/efeitos dos fármacos , Filamentos Intermediários/fisiologia , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Proteína Básica da Mielina/metabolismo , Oligossacarídeos/química , Oligossacarídeos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Traumatismos da Medula Espinal/fisiopatologia , Serina-Treonina Quinases TOR/metabolismo , Triterpenos/administração & dosagem , Triterpenos/química , Ácido Ursólico
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