Chikusetsu saponin IVa attenuates isoprenaline-induced myocardial fibrosis in mice through activation autophagy mediated by AMPK/mTOR/ULK1 signaling.
Phytomedicine
; 58: 152764, 2019 May.
Article
en En
| MEDLINE
| ID: mdl-31005723
ABSTRACT
BACKGROUND:
Myocardial fibrosis is a common pathological manifestation of many cardiovascular diseases at the end stage. Autophagy has been demonstrated to play a protective role in the cardiac fibrosis. Our previous studies have demonstrated that the Saponins from Panax japonicus effectively ameliorated the degree of fibrosis in rat acute myocardial ischemia injury model though the mechanisms are not clear.HYPOTHESIS:
We hypothesized that Chikusetsusaponin IVa (CS), a major component of Saponins from Panaxjaponicus, may improve isoprenaline induced myocardial fibrosis via AMPK/mTOR/ULK1 mediated autophagyMETHODS:
Continuous subcutaneous injection of isoproterenol for 21 days was used to induce myocardial fibrosis in mice and high and low doses (15â¯mg/kg and 5â¯mg/kg) of CS was administered by oral gavage to observe the efficacy. Animals were sacrificed 12 h after the last administration and samples were collected. H&E staining, Masson staining and wheat germ agglutinin (WGA) staining were used to evaluate histopathological changes, collagen deposition and myocardial cell hypertrophy. Autophagy-related markers (LC3ß, Beclin1 and p62) and AMPK/mTOR/ULK1 pathway-related markers were evaluated by western blot.RESULTS:
CS effectively attenuated isoprenaline-induced myocardial fibrosis in vivo, reduced the heart index, inhibited inflammatory infiltration, decreased collagen deposition and myocardial cell size. CS treatment rescued the expression of autophagy-related markers. CS activated autophagy through the activation of AMPK, which in turn inhibited the phosphorylation of mTOR and ULK1(Ser757), rather than directly phosphorylate ULK1(Ser555) by AMPK.CONCLUSION:
Our data demonstrated that CS attenuated isoprenaline-induced myocardial fibrosis by activating autophagy through AMPK/mTOR/ULK1 pathway. Our findings suggested that CS is a potential candidate drug against cardiac fibrosis and have identified potential drug targets for the treatment of heart diseases.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Ácido Oleanólico
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Saponinas
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Autofagia
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Corazón
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Isoproterenol
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Miocardio
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Phytomedicine
Año:
2019
Tipo del documento:
Article