Deciphering the Mechanism of Xijiao Dihuang Decoction in Treating Psoriasis by Network Pharmacology and Experimental Validation

Yicheng Guo; Huiqun Gan; Shigui Xu; Guosheng Zeng; Lili Xiao; Zhijun Ding; Jie Zhu; Xinglong Xiong; Zhiyuan Fu

doi:10.2147/DDDT.S417954

Deciphering the Mechanism of Xijiao Dihuang Decoction in Treating Psoriasis by Network Pharmacology and Experimental Validation

Drug Des Devel Ther. 2023 Sep 12:17:2805-2819. doi: 10.2147/DDDT.S417954. eCollection 2023.

Authors

Yicheng Guo¹, Huiqun Gan¹, Shigui Xu¹, Guosheng Zeng², Lili Xiao², Zhijun Ding², Jie Zhu³, Xinglong Xiong³, Zhiyuan Fu¹

Affiliations

¹ Department of Pharmacy, Dermatology Hospital of Jiangxi Province, Nanchang, People's Republic of China.
² Jiangxi Provincial Clinical Research Center for Skin Diseases, Nanchang, People's Republic of China.
³ Candidate Branch of National Clinical Research Center for Skin Diseases, Nanchang, People's Republic of China.

Abstract

Purpose: This study aims to confirm the efficacy of Xijiao Dihuang decoction (XJDHT), a classic prescription, in treating psoriasis and to explore the potential therapeutic mechanism.

Methods: For pharmacodynamic analysis, a mouse model of imiquimod cream (IMQ)-induced psoriasis was constructed. Active ingredients and genes of XJDHT, as well as psoriasis-related targets, were obtained from public databases. Intersecting genes (IGEs) of XJDHT and psoriasis were collected by Venn Diagram. A protein-protein interaction (PPI) network of IGEs is constructed through the STRING database. The Molecular Complex Detection (MCODE) and Cytohubba plug-ins of Cytoscape software were used to identified hub genes. In addition, we conducted enrichment analysis of IGEs using the R package clusterProfiler. Hub genes were validated via external GEO databases. The influence of XJDHT on Hub gene expression was examined by qPCR and ELISA, and molecular docking was used to evaluate the binding efficacy between active ingredients and hub genes.

Results: The results revealed that XJDHT possesses 92 potential genes for psoriasis, and 8 Hub genes were screened. Enrichment analysis suggested that XJDHT ameliorate psoriasis through multiple pathways, including AGE-RAGE, HIF-1, IL-17 and TNF signaling pathway. Validation data confirmed the differential expression of IL6, VEGFA, TNF, MMP9, STAT3, and TLR4. Molecular docking revealed a strong affinity between active ingredients and Hub genes. The efficacy of XJDHT in improving psoriatic lesions in model mice was demonstrated by PASI score and HE staining, potentially attributed to the down-regulation of VEGFA, MMP9, STAT3, TNF, and IL-17A, as evidenced by ELISA and qPCR.

Conclusion: This study employed network pharmacology and in vitro experiments to identify the potential mechanisms underlying the therapeutic effects of XJDHT on psoriasis, providing a new theoretical basis for its clinical application in the treatment of psoriasis.

Keywords: Xijiao Dihuang decoction; angiogenesis; molecular docking; network pharmacology; psoriasis.

MeSH terms

Animals
Databases, Factual
Matrix Metalloproteinase 9
Mice
Molecular Docking Simulation
Network Pharmacology*
Psoriasis* / drug therapy

Substances

Matrix Metalloproteinase 9