# Mechanism of Astragalus membranaceus (Huangqi, HQ) for treatment of heart failure based on network pharmacology and molecular docking

## TL;DR

This study explores how Astragalus membranaceus (Huangqi) may help treat heart failure by identifying key compounds and their effects on heart cells and inflammation.

## Contribution

The study identifies five key active ingredients in Astragalus membranaceus that may protect the heart by regulating ESR1 expression and reducing inflammation.

## Key findings

- Five active ingredients of Astragalus membranaceus reduced cell enlargement and expression of heart failure markers in cardiomyocytes.
- These compounds inhibited inflammation by lowering TNF-α, IL-1β, IL-18, and IL-6 levels in Ang II-induced cardiomyocytes.
- Molecular docking showed strong binding of the compounds to ESR1, with some promoting ESR1 and phosphorylated ESR1 expression.

## Abstract

Heart failure is a leading cause of death in the elderly. Traditional Chinese medicine, a verified alternative therapeutic regimen, has been used to treat heart failure, which is less expensive and has fewer adverse effects. In this study, a total of 15 active ingredients of Astragalus membranaceus (Huangqi, HQ) were obtained; among them, Isorhamnetin, Quercetin, Calycosin, Formononetin, and Kaempferol were found to be linked to heart failure. Ang II significantly enlarged the cell size of cardiomyocytes, which could be partially reduced by Quercetin, Isorhamnetin, Calycosin, Kaempferol, or Formononetin. Ang II significantly up‐regulated ANP, BNP, β‐MHC, and CTGF expressions, whereas Quercetin, Isorhamnetin, Calycosin, Kaempferol or Formononetin treatment partially downregulated ANP, BNP, β‐MHC and CTGF expressions. Five active ingredients of HQ attenuated inflammation in Ang II‐induced cardiomyocytes by inhibiting the levels of TNF‐α, IL‐1β, IL‐18 and IL‐6. Molecular docking shows Isorhamnetin, Quercetin, Calycosin, Formononetin and Kaempferol can bind with its target protein ESR1 in a good bond by intermolecular force. Quercetin, Calycosin, Kaempferol or Formononetin treatment promoted the expression levels of ESR1 and phosphorylated ESR1 in Ang II‐stimulated cardiomyocytes; however, Isorhamnetin treatment had no effect on ESR1 and phosphorylated ESR1 expression levels. In conclusion, our results comprehensively illustrated the bioactives, potential targets, and molecular mechanism of HQ against heart failure. Isorhamnetin, Quercetin, Calycosin, Formononetin and Kaempferol might be the primary active ingredients of HQ, dominating its cardioprotective effects against heart failure through regulating ESR1 expression, which provided a basis for the clinical application of HQ to regulate cardiac hypertrophy and heart failure.