Andrographolide attenuates skeletal muscle dystrophy in mdx mice and increases efficiency of cell therapy by reducing fibrosis
Cargando...
Archivos
Fecha
2014-03
Profesor/a Guía
Facultad/escuela
Idioma
en
Título de la revista
ISSN de la revista
Título del volumen
Editor
BioMed Central Ltd.
Nombre de Curso
Licencia CC
Atribution 4.0 International (CC BY 4.0)
Licencia CC
https://creativecommons.org/licenses/by/4.0/deed.es
Resumen
Background: Duchenne muscular dystrophy (DMD) is characterized by the absence of the cytoskeletal protein
dystrophin, muscle wasting, increased transforming growth factor type beta (TGF-β) signaling, and fibrosis. At the
present time, the only clinically validated treatments for DMD are glucocorticoids. These drugs prolong muscle
strength and ambulation of patients for a short term only and have severe adverse effects. Andrographolide, a
bicyclic diterpenoid lactone, has traditionally been used for the treatment of colds, fever, laryngitis, and other
infections with no or minimal side effects. We determined whether andrographolide treatment of mdx mice, an
animal model for DMD, affects muscle damage, physiology, fibrosis, and efficiency of cell therapy.
Methods: mdx mice were treated with andrographolide for three months and skeletal muscle histology, creatine
kinase activity, and permeability of muscle fibers were evaluated. Fibrosis and TGF-β signaling were evaluated by
indirect immunofluorescence and Western blot analyses. Muscle strength was determined in isolated skeletal
muscles and by a running test. Efficiency of cell therapy was determined by grafting isolated skeletal muscle
satellite cells onto the tibialis anterior of mdx mice.
Results: mdx mice treated with andrographolide exhibited less severe muscular dystrophy than untreated
dystrophic mice. They performed better in an exercise endurance test and had improved muscle strength in
isolated muscles, reduced skeletal muscle impairment, diminished fibrosis and a significant reduction in TGF-β
signaling. Moreover, andrographolide treatment of mdx mice improved grafting efficiency upon intramuscular
injection of dystrophin-positive satellite cells.
Conclusions: These results suggest that andrographolide could be used to improve quality of life in individuals
with DMD.
Notas
Indexación: Scopus.
Palabras clave
Andrographolide, Mdx, DMD, Fibrosis, Skeletal Muscle, Cell Therapy
Citación
Skeletal Muscle. Volume 4, Issue 1. 21 March 2014. Article number 6
DOI
DOI: 10.1186/2044-5040-4-6