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Aim Inflammation and fibrosis have been shown to be critical factors in heart failure (HF) progression. Calycosin (Cal) is the major active component of Astragalus mongholicus Bunge and has been reported to have therapeutic effects on the cardiac dysfunction after myocardial infarction. However, whether Cal could ameliorate myocardial infarction (MI)-induced inflammation and fibrosis and precise mechanisms remain uncertain. The aim of this study is to explore the role of Cal in HF and to clarify the underlying mechanisms. Methods For in