Yunshan Wang, Yangyang Zhang, Kexin Li, Zihu Wang, Jia Wang, Qian Li
Current mainstream treatment of chronic obstructive pulmonary disease (COPD) relies largely on long-acting β2-adrenergic receptor (β2AR) agonists and muscarinic M3 receptor (M3R) antagonists, yet residual inflammation and variable treatment responses persist. Developing therapeutics from multicomponent herbal medicines is an effective drug development approach but is constrained by the difficulty of linking individual constituents to pharmacologically relevant targets and in vivo efficacy. This study established an integrated discovery workflow combining whole-formula efficacy testing, receptor-affinity chromatography, mass spectrometry (MS), and in vivo validation of candidate combinations. We applied this workflow to the Shaoqitongfei formula (SQTF), an investigator-developed three-herb prescription evaluated for ameliorating COPD, and selected the β2AR and M3R as clinically relevant bronchodilator targets. In porcine pancreatic elastase/lipopolysaccharide (LPS)-induced COPD mice, SQTF improved respiratory parameters, attenuated lung injury, and reduced inflammatory cytokine levels in serum and bronchoalveolar lavage fluid. Affinity columns containing immobilized β2AR and M3R stationary phases were utilized to screen the receptor-targeting components in formula extract. High-performance liquid chromatography-tandem MS analysis tentatively annotated albiflorin and kaempferol in the extract retained by both columns. In rats exposed to cigarette smoke and LPS, co-administration of albiflorin and kaempferol reproduced several of the pulmonary and anti-inflammatory effects of SQTF and shifted protein-expression patterns associated with signaling proteins to those observed in controls. Taken together, these findings establish a receptor-guided workflow for selecting pharmacologically relevant constituent combinations from complex herbal medicines and provide an analytical basis for the further development of SQTF-derived therapies for COPD.