Article ; Online: AstragalosideⅣ against cardiac fibrosis by inhibiting TRPM7 channel.
Phytomedicine : international journal of phytotherapy and phytopharmacology
2017 Volume 30, Page(s) 10–17
Abstract: ... The moderate inhibition of the TRPM7 channel may be a new strategy for treating cardiac fibrosis. ... channel in hypoxia-induced cardiac fibrosis.: Conclusion: Our results suggest that the inhibition ... potential cation channel, subfamily M, member 7 (TRPM7) by in vivo and in vitro experiments.: Methods ...
| Abstract | Background: Astragaloside Ⅳ (ASG-Ⅳ, (Fig. 1) is the most active component of Chinese sp. Astragalus membranaceus Bunge (Fabaceae) that has showed antioxidant, antiapoptotic and antiviral activities among others. It is reported to play an important role in cardiac fibrosis (CF), but the mechanism remains unclear. Purpose: To investigate the mechanism of ASG-Ⅳ on inhibiting myocardial fibrosis induced by hypoxia. Study design: We studied the relationship between anti-fibrotic effect of ASG-Ⅳ and transient receptor potential cation channel, subfamily M, member 7 (TRPM7) by in vivo and in vitro experiments. Methods: In vivo, CF was induced by subcutaneous isoproterenol (ISO) for 10 days. Rat hearts were resected for histological experiment and reverse transcription real-time quantitative poly merase chain reaction (RT-qPCR). In vitro, molecular and cellular biology technologies were used to confirm the anti-fibrosis effect underlying mechanism of ASG-Ⅳ. Results: Histological findings and the collagen volume fraction showed that ASG-Ⅳ decreased fibrosis in heart tissues. Hypoxia could stimulate the proliferation and differentiation of cardiac fibroblast which indicated that the degree of fibrosis was increased significantly. Anoxic treatment could also obviously up-regulate the expression of TRPM7 protein and current. ASG-Ⅳ groups showed the opposite results. Knock-down TRPM7 experiment further confirmed the role of TRPM7 channel in hypoxia-induced cardiac fibrosis. Conclusion: Our results suggest that the inhibition of hypoxia-induced CF in vivo and in vitro by ASG-IV is associated with reduction of the expression of TRPM7. The moderate inhibition of the TRPM7 channel may be a new strategy for treating cardiac fibrosis. |
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| MeSH term(s) | Animals ; Cell Differentiation/drug effects ; Cell Hypoxia/drug effects ; Cell Proliferation/drug effects ; Endomyocardial Fibrosis/chemically induced ; Endomyocardial Fibrosis/drug therapy ; Endomyocardial Fibrosis/metabolism ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Heart/drug effects ; Isoproterenol/pharmacology ; Isoproterenol/toxicity ; Male ; Mice ; NIH 3T3 Cells/drug effects ; Rats ; Rats, Sprague-Dawley ; Saponins/pharmacology ; TRPM Cation Channels/genetics ; TRPM Cation Channels/metabolism ; Triterpenes/pharmacology ; Up-Regulation |
| Chemical Substances | Saponins ; TRPM Cation Channels ; Triterpenes ; astragaloside A (3A592W8XKE) ; Trpm7 protein, rat (EC 2.7.11.1) ; Isoproterenol (L628TT009W) |
| Language | English |
| Publishing date | 2017-07-01 |
| Publishing country | Germany |
| Document type | Journal Article |
| ZDB-ID | 1205240-1 |
| ISSN | 1618-095X ; 0944-7113 |
| ISSN (online) | 1618-095X |
| ISSN | 0944-7113 |
| DOI | 10.1016/j.phymed.2017.04.002 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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