Systems pharmacology of traditional Chinese medicine in fibrosis: From multi-target mechanisms to translational validation

Systems biology research has integrated network pharmacology with clinical data to investigate traditional Chinese Medicine (TCM) antifibrotic mechanisms across multiple biological pathways. These combined approaches draw on chemical-protein interaction databases, transcriptomic and metabolomic profiling, protein–protein interaction networks, molecular docking, randomized trial and large cohort study evidence. Yinchenhao Decoction, Danggui Liuhuang Decoction, Curcumae Rhizoma (Ezhu in Chinese)- Astragali Radix (Huangqi in Chinese) herb pair, and Angelicae Sinensis Radix (Danggui in Chinese)- Chuanxiong Rhizoma (Chuanxiong in Chinese) herb pair regulate transforming growth factor- β (TGF- β )/mothers against decapentaplegic homolog (Smad), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), nuclear factor- κ B (NF- κ B), mitogen-activated protein kinase (MAPK), and janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways. Integration of these signals is associated with suppression of inflammation, altered regulation of apoptosis, modulation of cellular activation, and extracellular matrix remodeling in hepatic, cardiac, and pulmonary fibrosis models. This multi-layered framework offers a rational basis for hypothesis generation in drug repositioning and development of novel antifibrotic candidates, although clinical validation remains limited and further rigorous trials are warranted.