Xiaoyin granules relieve skin lesions in mice with psoriasis through by EGFR-related pathway

Abstract

Background: Psoriasis is a common relapsing chronic inflammatory skin disease, characterized by immune cell infiltration and abnormal proliferation of keratinocytes. Long-term clinical practice has shown that optimized Xiaoyin granules (XYKL) has benefits for patients with mild to moderate psoriasis, and there are no significant adverse reactions. However, the mechanism of action has not been fully deciphered. Objective: This study aims to explore the potential mechanism of XYKL in treating psoriasis through network pharmacology and experimental validation. Methods: The ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) technique was employed to determine the main components of XYKL. Network pharmacology and molecular docking technology were utilized to screen the active components-targets-pathways for treating psoriasis with XYKL. Additionally, a psoriasis mouse model was created based on the predicted outcomes, and both in vivo and in vitro experiments were conducted to validate the findings. Results: Through network pharmacology analysis, 22 effective ingredients and 70 potential targets associated with psoriasis were selected for XYKL. The “compound-target” network was constructed based on the relationship between compounds and targets. Through PPI network analysis, 26 targets including AKT1, STAT3, EGFR, SRC, ESR1, MMP9, KDR, GSK3B, IL2, and MMP2 were screened. Then, through Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the “ingredient-target-pathway-disease” network was established for these targets. Finally, 10 important chemical ingredients were selected from XYKL, which act on 17 important targets and regulate 13 psoriasis-related biological pathways. In the research conducted in psoriasis mouse models and in vitro cell experiments, it was found that XYKL significantly inhibits the inflammatory levels in psoriasis mice and may promote apoptosis of human immortalized keratinocytes (HaCaT) by inhibiting the EGFR-related signaling pathway and inhibiting their proliferation. Conclusion: This study confirmed the therapeutic effect of XYKL on psoriasis and discovered that XYKL may achieve this effect by inhibiting the EGFR-related signaling pathway to alleviate the inflammatory response of psoriasis, while also inhibiting the proliferation of keratinocytes and promoting their apoptosis.