Integrating UPLC–Q-TOF–MS and network pharmacology to analyze the components and mechanism of action of Compound Duzhong Zhuangyao Capsules on osteoporosis

Although Compound Duzhong Zhuangyao Capsules (Co-DZZY Capsules) are used to treat lumbago and knee weakness caused by osteoporosis (OP), the underlying mechanisms involved remain unclear. Therefore, this study aimed to investigate the active components of Co-DZZY Capsules and the involved mechanisms for the treatment of OP. The components of the Co-DZZY Capsules were tentatively identified using ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry, and their targets were retrieved from the Swiss Target Prediction database. OP-related targets were obtained from the Gene Cards database. A protein-protein interaction network was constructed using the STRING data platform, and the compound-target-disease visualization network was established using Cytoscape software (Cytoscape Consortium, San Diego). Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses were performed using the DAVID database. The AutoDock software (Molecular Graphics Laboratory at The Scripps Research Institute [TSRI], San Diego) was used to verify molecular docking between the selected components and core targets. In total, 92 compounds were identified, whose 101 predicted targets were associated with OP. The potential active ingredients included luteolin, allocryptopine, kaempferol, isobavachin, and albiflorin. The core targets identified were threonine-protein kinase, interleukin-6, tumor necrosis factor alpha, peroxisome proliferator-activated receptor gamma, signal transducer and activator of transcription 3, and tyrosine-protein kinase. Kyoto encyclopedia of genes and genomes analysis revealed that Co-DZZY Capsules activate the advanced glycation end product receptor for advanced glycation end products, hypoxia inducible factor-1, phosphatidylinositol 3-kinase-protein kinase B, tumor necrosis factor alpha, and ras-related protein 1 signaling pathways, and other signaling pathways via the core targets, and are involved in positive regulation of protein kinases, smooth muscle cell proliferation, cell migration, and other biological processes. Molecular docking revealed that the core targets were stably bound to the corresponding compounds. This study provides a scientific basis for analyzing the bioactive compounds in Co-DZZY Capsules and their pharmacological mechanisms of action.