Andrographolide attenuates skeletal muscle dystrophy in mdx mice and increases efficiency of cell therapy by reducing fibrosis

dc.contributor.authorCabrera, D.
dc.contributor.authorGutiérrez, J.
dc.contributor.authorCabello Verrugio, Claudio Alejandro
dc.contributor.authorMorales, M. G.
dc.contributor.authorMezzano, S.
dc.contributor.authorFadic Ruiz, Ricardo Julio Nicolás
dc.contributor.authorCasar Leturia, Juan Carlos
dc.contributor.authorHancke, J. L.
dc.contributor.authorBrandan, Enrique
dc.date.accessioned2020-01-14T01:29:00Z
dc.date.available2020-01-14T01:29:00Z
dc.date.issued2014
dc.description.abstractBackground: 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.
dc.identifier.doi10.1186/2044-5040-4-6
dc.identifier.issn2044-5040
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/27461
dc.identifier.urihttps://doi.org/10.1186/2044-5040-4-6
dc.issue.numeroNo. 1
dc.language.isoen
dc.nota.accesoContenido completo
dc.revistaSkeletal Musclees_ES
dc.rightsacceso abierto
dc.subjectAndrographolidees_ES
dc.subjectCell therapyes_ES
dc.subjectDMDes_ES
dc.subjectFibrosises_ES
dc.subjectmdxes_ES
dc.subjectSkeletal musclees_ES
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.titleAndrographolide attenuates skeletal muscle dystrophy in mdx mice and increases efficiency of cell therapy by reducing fibrosises_ES
dc.typeartículo
dc.volumenVol. 4
sipa.codpersvinculados126029
sipa.codpersvinculados14151
sipa.codpersvinculados134336
sipa.codpersvinculados4922
sipa.codpersvinculados51912
sipa.codpersvinculados1322
sipa.codpersvinculados176700
sipa.codpersvinculados52075
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