[Patterns and mechanisms of the "treating skin with skin" therapy under traditional Chinese medicine analogical thinking based on data mining and network pharmacology].

OBJECTIVES: Under the guidance of analogical thinking in traditional Chinese medicine (TCM), the "treating of skin with skin" therapy, using processed animal and plant skin-derived medicinal materials to treat skin diseases, has a long history but lacks scientific evidence-based support. This study aims to apply data mining and network pharmacology techniques to explore the prescription patterns and mechanisms of action of the "treating skin with skin" therapy, and to interpret its rationality, effectiveness, and scientific basis using modern scientific methods.

METHODS: Relevant literature from Chinese and English databases over the past 20 years was retrieved and integrated according to inclusion and exclusion criteria. Data were integrated and mined using software such as Excel, OriginPro 2021, and SPSS Modeler 18.0. Frequency analysis, cluster analysis, and association rule analysis were performed sequentially to summarize high-frequency plant skin-derived Chinese medicinal materials and extract the core prescription. Core prescription drugs and skin disease-related gene targets were obtained from drug and disease target databases, including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and GeneCards. Intersection targets were identified using Venny 2.1.0, and core targets were further extracted. Protein-protein interaction (PPI) network analysis, Gene Ontology (GO) functional enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted for the intersection targets, and finally a "core drug-component-target-pathway" network was constructed and visualized.

RESULTS: Based on the inclusion and exclusion criteria, 563 eligible articles were ultimately included, from which 32 prescriptions were extracted, involving 21 plant skin-derived Chinese medicinal materials. Among them, 15 medicinal materials had a usage frequency exceeding 50%, with bitter, sweet, and cold properties predominating. Cluster analysis yielded 4 effective clusters. Cluster 1: Phellodendron cortex-Dictamni cortex; Cluster 2: Eucommia cortex-Mori cortex-Meliae cortex-Pseudolaricis cortex; Cluster 3: Moutan cortex-Poriae Cutis-Lycii cortex-Fraxini cortex-Acanthopanacis cortex-Benincasae Pericarpium; Cluster 4: Ailanthi cortex-Periplocae cortex-Erycibes cortex. Association rule analysis generated 92 association rules, with 4 strong links, 90 moderate links, and 10 weak links between herb pairs. Based on the association rules and linkage strength, the core prescription of the "treating skin with skin" therapy was summarized as "Phellodendri Cortex-Moutan Cortex-Dictamni Cortex-Benincasae Pericarpium-Poriae Cutis-Lycii Cortex." A total of 46 active ingredients were screened from this core prescription, involving 781 gene targets. A total of 2 537 skin disease-related gene targets were retrieved, yielding 212 intersection targets between the core prescription and the disease. PPI network analysis of the intersection targets showed 2 723 edges among 212 nodes, with an average node degree of 25.9 and an average local clustering coefficient of 0.554. The PPI network of core targets contained 50 nodes and 784 edges; the top three core nodes by degrees were interleukin-6 (IL-6; 116), tumor necrosis factor (TNF; 115), and interleukin-1 beta (IL-1β; 110). GO analysis yielded 732 biological process terms, with the top 3 being response to lipopolysaccharide, positive regulation of DNA-templated transcription, and positive regulation of microRNA (miRNA) transcription; 90 cellular component terms, with the top 3 being extracellular space, extracellular region, and chromatin; and 153 molecular function terms, with the top 3 being enzyme binding, nuclear receptor activity, and identical protein binding. KEGG analysis identified 166 enriched signaling pathways, with the top 3 being pathways in cancer, lipid and atherosclerosis, and the advanced glycation end products-receptor for advanced glycation end products pathway in diabetic complications. The visualized "core drug-component-target-pathway" network comprised 854 nodes and 1 911 edges, with a network centralization coefficient of 0.182 and a characteristic path length of 3.985; the top 3 nodes by degree were all drug components, namely vitamin E, vitamin B, and trigonelline.

CONCLUSIONS: Guided by TCM analogical thinking, the core prescription of the "treating skin with skin" therapy exerts therapeutic effects on skin diseases through synergistic actions involving multiple components, multiple targets, and multiple pathways. Its effect is significant, the rationale is well founded, and its origins are well established.