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 vivo experiments, rats underwent left anterior descending artery
ligation for
heart failure model, and the cardioprotective effects of Cal were measured by echocardiographic assessment and histological examination.
RNA-seq approach was applied to explore potential differential genes and pathways. For further mechanistic study, proinflammatory-
conditioned media (
conditioned media)-induced H9C2 cell injury model and TGFβ-stimulated cardiac fibroblast model were applied to determine the regulatory mechanisms of Cal. Results: In the in vivo experiments, echocardiography results showed that Cal significantly improved heart function. GO and reactome enrichment revealed that
inflammation and
fibrosis pathways are involved in the Cal-treated group. KEGG enrichment indicated that the PI3K-AKT pathway is enriched in the Cal-treated group. Further experiments proved that Cal alleviated cardiomyocyte inflammatory responses evidenced by downregulating the expressions of phosphorylated IκB
kinase α/β (p-IKKα/β), phosphorylated nuclear factor kapa B (p-NFκB), and
tumor necrosis factor α (TNFα). Besides, Cal effectively attenuated cardiac
fibrosis through the inhibitions of expressions and depositions of
collagen I and
collagen III. In the in vitro experiments, the
phosphatidylinositol three
kinase (PI3K) inhibitor
LY294002 could abrogate the anti-
inflammation and antifibrosis
therapeutic effects of Cal, demonstrating that the cardioprotective effects of Cal were mediated through upregulations of PI3K and
serine/threonine kinase (AKT). Conclusion: Cal inhibited
inflammation and
fibrosis via activation of the PI3K-AKT pathway in H9C2 cells, fibroblasts, and
heart failure in postacute
myocardial infarction rats.