Network pharmacology-based analysis to explore the therapeutic mechanism of Cortex Dictamni on atopic dermatitis

J Ethnopharmacol. 2023 Mar 25:304:116023. doi: 10.1016/j.jep.2022.116023. Epub 2022 Dec 17.

Abstract

Ethnopharmacological relevance: Dermatitis is a common clinical chronic inflammatory skin disease, which incidence has been on the rise in recent years. It not only seriously affects the physical and mental health of patients but also increase economic burden. Currently, commonly used drugs such as corticosteroids, anti-histamines have certain side effects or are expensive. Therefore, the search for an alternative therapy for dermatitis has important clinical significance. Cortex Dictamni is a commonly used traditional Chinese medicine for expelling wind and itching, but its mechanism for treating dermatitis is still unclear.

Materials and methods: Network pharmacological analysis was performed to predict the potential targets and pathways of Cortex Dictamni against dermatitis. Molecular docking was used to assess the binding affinity of active compounds and core targets. By repeatedly stimulating the ears with 1-fluoro-2,4-dinitrobenzene (DNFB), an atopic dermatitis (AD) mouse model was established in order to study the anti-dermatitis effect of Cortex Dictamni. The skin thickness and inflammatory cell infiltration in mouse ears were assessed by tissue staining and flow cytometric. The levels of inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA), and the total protein and phosphorylation levels of related pathways were analyzed by western blotting.

Results: In this study, 11 active ingredients, 122 Cortex Dictamni and dermatitis intersection targets were identified. The results from Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the core targets were mainly enriched in immune response and inflammatory signaling pathways. AD mice treated with ethanol extract of Cortex Dictamni (ECD) improved the symptoms of ear skin lesions, alleviated epidermis and dermis thickening of the AD mice ears, decreased pathological immune cell infiltration and attenuated the levels of inflammatory cytokines (TLR4, IL-6, IL-17), and inhibited the hyperactivation of the PI3K-AKT, JAK1-STAT3/STAT6 signal pathways.

Conclusions: Cortex Dictamni can improve the symptoms of skin lesions and the degree of inflammation caused by AD, and may inhibit AD through multiple pathways, such as regulating PI3K-AKT and JAK1-STAT3/STAT6 pathways. These results not only provide experimental evidence for the clinical application of Cortex Dictamni but also provide some help for the research and development of dermatitis drugs.

Keywords: Atopic dermatitis; Cortex Dictamni; Inflammation; Network pharmacology; Traditional Chinese medicine.

MeSH terms

  • Animals
  • Dermatitis, Atopic* / pathology
  • Drugs, Chinese Herbal* / pharmacology
  • Drugs, Chinese Herbal* / therapeutic use
  • Mice
  • Molecular Docking Simulation
  • Network Pharmacology
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Skin Diseases* / drug therapy

Substances

  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Drugs, Chinese Herbal