Astragalus Mongholicus for Idiopathic Pulmonary Fibrosis Treatment: From Molecules to Systems

Abstract: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease with limited treatment options. Astragalus mongholicus (AM), a cornerstone herb in traditional Chinese medicine (TCM), demonstrates significant therapeutic potential for IPF due to its multi-target mechanisms. This review synthesizes evidence on AM and its bioactive components; astragalus polysaccharide (APS), astragaloside IV (AS IV), and calycosin (CAL) in targeting key IPF pathological processes. These include suppression of inflammatory responses (via TLR4/NF-κB inhibition), inhibition of extracellular matrix deposition (via MMP/TIMP modulation), attenuation of oxidative stress, regulation of autophagy, and blockade of epithelial-mesenchymal transition (via lncRNA-ATB/miR-200c/ZEB1 axis). We further highlight the integration of molecularlevel mechanisms with systems pharmacology to elucidate AM’s holistic actions. Clinical studies support AM-containing TCM prescriptions in improving lung function with fewer adverse effects. This synthesis underscores AM’s promise as a multi-target therapeutic agent and advocates for systematic pharmacology approaches in future IPF drug development.