Astragaloside IV inhibits cardiac fibrosis via miR-135a-TRPM7-TGF-ß/Smads pathway.
J Ethnopharmacol
; 249: 112404, 2020 Mar 01.
Article
en En
| MEDLINE
| ID: mdl-31739105
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE Cardiac fibrosis is a common characteristic of many cardiac diseases. Our previous results showed that TRPM7 channel played an important role in the fibrosis process. MicroRNA-135a was reported to get involved in the fibrotic process. Astragalus membranaceus (Fisch.) Bunge was widely used in Chinese traditional medicine and showed cardiac protective effects in previous researches. Astragaloside IV(ASG), which is regarded as the most important ingredient of Astragalus, has been showed the effect of cardiac protection via various mechanisms, while no data suggested its action related to miRNAs regulation. AIM OF THE STUDY The objective of this article is to investigate the inhibition effect of ASG on cardiac fibrosis through the miR-135a-TRPM7-TGF-ß/Smads pathway. MATERIALS AND METHODS:
We extracted the active components from herb according to the paper and measured the content of ASG from the mixture via HPLC. The inhibition potency of cardiac hypertrophy between total extract of Astragalus and ASG was compared. SD rats were treated with ISO (5â¯mg/kg/day) subcutaneously (s.c.) for 14 days, ASG (10â¯mg/kg/d) and Astragalus extract (AE) (4.35â¯g/kg/d, which contained about ASG 10â¯mg) were given p.o. from the 6th day of the modeling. Cardiac fibroblasts (CFs) of neonatal rats were incubated with ISO (10⯵M) and treated with ASG (10⯵M) simultaneously for 24â¯h.RESULTS:
The results showed that both AE and ASG treatment reduced the TRPM7 expression from the gene level and inhibited cardiac fibrosis. ASG group showed similar potency as the AE mixture. ASG treatment significantly decreased the current, mRNA and protein expression of TRPM7 which was one of targets of miR-135a. The activation of TGF-ß/Smads pathway was suppressed and the expression of α-SMA and Collagen I were also decreased obviously. In addition, our results showed that there was a positive feedback between the activation of TGF-ß/Smads pathway and the elevation of TRPM7, both of which could promote the development of myocardial fibrosis.CONCLUSIONS:
AE had the effect of cardiac fibrosis inhibition and decreased the mRNA expression of TRPM7. ASG, as one of the effective ingredients of AE, showed the same potency when given the same dose. ASG inhibited cardiac fibrosis by targeting the miR-135a-TRPM7-TGF-ß/Smads pathway.Palabras clave
Texto completo:
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Bases de datos:
MEDLINE
Medicinas Tradicionales:
Medicinas_tradicionales_de_asia
/
Medicina_china
Métodos Terapéuticos y Terapias MTCI:
Terapias_biologicas
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Plantas_medicinales
Asunto principal:
Saponinas
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Triterpenos
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Cardiomiopatía Hipertrófica
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Extractos Vegetales
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Transducción de Señal
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Miocardio
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
Idioma:
En
Revista:
J Ethnopharmacol
Año:
2020
Tipo del documento:
Article