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

Daniel Cabrera, Jaime Gutiérrez, Claudio Cabello-Verrugio, Maria G. Morales, Sergio Mezzano, Ricardo Fadic, Juan C. Casar, Juan L. Hancke, Enrique Brandan

Resultado de la investigación: Article

20 Citas (Scopus)

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.

Idioma originalEnglish
Número de artículo6
PublicaciónSkeletal Muscle
Volumen4
N.º1
DOI
EstadoPublished - 21 mar 2014

Huella dactilar

Inbred mdx Mouse
Cell- and Tissue-Based Therapy
Skeletal Muscle
Fibrosis
Duchenne Muscular Dystrophy
Muscle Strength
Muscles
Dystrophin
Skeletal Muscle Satellite Cells
MM Form Creatine Kinase
Laryngitis
Cytoskeletal Proteins
Muscular Dystrophies
Diterpenes
Intramuscular Injections
Lactones
Therapeutics
Indirect Fluorescent Antibody Technique
Exercise Test
Transforming Growth Factor beta

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Molecular Biology
  • Cell Biology

Citar esto

Cabrera, Daniel ; Gutiérrez, Jaime ; Cabello-Verrugio, Claudio ; Morales, Maria G. ; Mezzano, Sergio ; Fadic, Ricardo ; Casar, Juan C. ; Hancke, Juan L. ; Brandan, Enrique. / Andrographolide attenuates skeletal muscle dystrophy in mdx mice and increases efficiency of cell therapy by reducing fibrosis. En: Skeletal Muscle. 2014 ; Vol. 4, N.º 1.
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title = "Andrographolide attenuates skeletal muscle dystrophy in mdx mice and increases efficiency of cell therapy by reducing fibrosis",
abstract = "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.",
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author = "Daniel Cabrera and Jaime Guti{\'e}rrez and Claudio Cabello-Verrugio and Morales, {Maria G.} and Sergio Mezzano and Ricardo Fadic and Casar, {Juan C.} and Hancke, {Juan L.} and Enrique Brandan",
year = "2014",
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Andrographolide attenuates skeletal muscle dystrophy in mdx mice and increases efficiency of cell therapy by reducing fibrosis. / Cabrera, Daniel; Gutiérrez, Jaime; Cabello-Verrugio, Claudio; Morales, Maria G.; Mezzano, Sergio; Fadic, Ricardo; Casar, Juan C.; Hancke, Juan L.; Brandan, Enrique.

En: Skeletal Muscle, Vol. 4, N.º 1, 6, 21.03.2014.

Resultado de la investigación: Article

TY - JOUR

T1 - Andrographolide attenuates skeletal muscle dystrophy in mdx mice and increases efficiency of cell therapy by reducing fibrosis

AU - Cabrera, Daniel

AU - Gutiérrez, Jaime

AU - Cabello-Verrugio, Claudio

AU - Morales, Maria G.

AU - Mezzano, Sergio

AU - Fadic, Ricardo

AU - Casar, Juan C.

AU - Hancke, Juan L.

AU - Brandan, Enrique

PY - 2014/3/21

Y1 - 2014/3/21

N2 - 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.

AB - 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.

KW - Andrographolide

KW - Cell therapy

KW - DMD

KW - Fibrosis

KW - mdx

KW - Skeletal muscle

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U2 - 10.1186/2044-5040-4-6

DO - 10.1186/2044-5040-4-6

M3 - Article

AN - SCOPUS:84899139530

VL - 4

JO - Skeletal Muscle

JF - Skeletal Muscle

SN - 2044-5040

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ER -