Longdan Xiegan Decoction (LXD) is a well-known traditional Chinese herbal formula with demonstrated inhibitory effects on inflammatory cells involved in uveitis. However, the principal functional component combinations and their underlying mechanisms remain unclear.To identify the key component group (KCG) and explore the potential mechanisms of LXD in uveitis treatment, we applied a network community detection model, functional response space analysis, and a reverse prediction model. The effectiveness of the KCG and the validity of our strategy were subsequently verified through MTT, nitric oxide (NO), and ELISA assays. Within the components-targets-pathogenic genes-disease (CTP) network, combining Huffman coding with a random walk algorithm revealed eight foundational acting communities (FACs) with significant functional relevance. Validation demonstrated that these FACs effectively represent the corresponding C-T network for uveitis therapy. Using a novel node importance calculation method, we constructed the functional response space and identified 349 effective proteins. From this, 54 components were selected and defined as the KCG. Pathway enrichment analysis indicated that KCG targets significantly influenced IL-17, Toll-like receptor, and T cell receptor signaling pathways, which are pivotal in uveitis pathogenesis. Experimental validation showed that key KCG components, quercetin and sitosterol, substantially inhibited nitric oxide production and modulated TNF-α and IFN-γ levels in lipopolysaccharide-stimulated RAW264.7 cells. This study elucidates the multi-component, multi-gene, and multi-pathway pharmacological mechanisms of LXD against uveitis through an integrated pharmacology approach. The findings provide a novel framework for future investigations into the anti-uveitis mechanisms of traditional Chinese medicine.
