Acne is a common dermatological condition in which inflammation plays a central role. Compound Huangbai Liquid (CHL), a well-known traditional Chinese medicine (TCM) formulation, has demonstrated notable clinical benefits for acne, yet its mechanistic basis has not been comprehensively clarified using an integrated network pharmacology strategy.We identified the bioactive constituents of CHL and their putative molecular targets using the BATMAN-TCM platform. Acne-associated genes were collected from GeneCards, DisGeNet, and OMIM. Potential therapeutic targets were screened through Venn analysis. Protein–protein interaction (PPI) mapping was conducted using the STRING database, and Cytoscape 3.9.1 was applied to construct the interaction network and extract core proteins. GO enrichment and KEGG pathway analyses were carried out using Metascape and bioinformatics.com.cn. Visualization of TCM-compound-target-disease associations and disease-target-pathway relationships was generated in Cytoscape. Lastly, a mouse acne model was used to experimentally validate the predicted mechanisms.A total of 165 active molecules, 1117 drug-related targets, 156 acne-associated genes, and 34 intersecting therapeutic targets were identified. Enriched biological functions mainly involved lipid-responsive processes, lipopolysaccharide-related signaling, and secretory regulation. CHL showed strong relevance to ten major pathways, including those associated with Chagas disease and cancer-related signaling. Animal testing confirmed that CHL markedly reduced inflammatory mediator levels and suppressed the TLR4/NF-κB/p38 MAPK pathway in the acne model.This work highlights the multi-compound, multi-target, and multi-pathway characteristics of CHL in combating acne, offering an expanded framework for understanding how traditional Chinese medicine exerts therapeutic effects in acne management.
