Psoriasis is a recurrent chronic inflammatory skin disease. Unlike many of the latest psoriasis treatments that only confer limited curative effects and have certain side effects, oxymatrine effectively improves severe plaque psoriasis with mild adverse reactions. Here, we explored the genes and pathways underlying the effects of oxymatrine on psoriasis. Briefly, patients with severe plaque psoriasis were treated with oxymatrine and their lesioned skin samples were sequenced by full-length transcriptomics. Next, the differentially expressed genes (DEGs) in psoriatic lesions were identified and compared in oxymatrine-treated patients and healthy controls, their genes were functionally annotated, and protein–protein interaction network analysis and immunohistochemistry were performed. Both Psoriasis Area and Severity Index (PASI) and Body Surface Area (BSA) scores were recovered significantly from all 16 patients (all p < 0.001). The number of DEGs in patients before and after oxymatrine treatment was 4232, and 4105 DEGs were found between the psoriasis group (before oxymatrine treatment) and the normal control group [p < 0.01, |log2 fold change, (FC)| >1.5]. While most of the DEGs recovered significantly after oxymatrine treatment, only 650 DEGs were observed between the psoriasis group (after oxymatrine treatment) and the normal control group (p < 0.01, |log2FC|> 1.5). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that 64 pathways were significantly activated after oxymatrine treatment (p < 0.05). Only 12 pathways were statistically significant between after oxymatrine treatment and the normal control group (p < 0 .05). Among all the restored pathways, the improvement of the IL-17 signaling pathway was the most significant (p = 1.18E-06). Gene loci of oxymatrine action was assessed by protein interaction analysis on 205 DEGs that were co-expressed in 5 patients before and after oxymatrine treatment (p < 0.05, FC > 1.5). After oxymatrine treatment, the expression of two mitosis-related genes namely, cyclin dependent kinase 1 (CDK1) and cyclin B1 (CCNB1), that affect cell proliferation recovered significantly. In light of these results, we conclude that oxymatrine likely alters the abnormal expression of some genes and pathways in psoriasis patients. Multipathway and multitarget therapy can greatly ameliorate abnormalities in genes and pathways and effectively treat psoriasis. Importantly, among the DEGs, the proliferation-related genes, such as CDK1 and CCNB1, are likely important targets for treating psoriasis by oxymatrine. We believe that these findings may lead to a new treatment strategy for psoriasis.

Psoriasis is a common, chronic, inflammatory, recurrent, immune-mediated skin disease. Oxymatrine is effective for treating moderate and severe psoriasis. Here, transcriptional changes in skin lesions before and after oxymatrine treatment of patients with psoriasis were identified using full-length transcriptome analysis and then compared with those of normal skin tissues. Patients and Methods: Co-expression modules were constructed by combining the psoriasis area and severity index (PASI) score with weighted gene co-expression network analysis to explore the action mechanism of oxymatrine in improving clinical PASI. The expression of selected genes was verified using immunohistochemistry, quantitative real-time PCR, and Western blotting. Results: Kyoto Encyclopedia of Gene and Genome pathway analysis revealed that oxymatrine treatment reversed the abnormal pathways, with an improvement in lesions and a reduction in PASI scores. Gene Ontology (GO) analysis revealed that oxymatrine treatment led to altered GO terms being regulated with a decrease in the PASI score in patients. Therefore, oxymatrine treatment may improve the skin barrier, differentiation of keratinocytes, and alleviate abnormality of organelles such as desmosomes. Protein-protein interaction network interaction analysis revealed that the top five hub genes among many interrelated genes were CNFN, S100A8, SPRR2A, SPRR2D, and SPRR2E, associated with the epidermal differentiation complex (EDC). EDC regulates keratinocyte differentiation. This result indicates that oxymatrine treatment can restore keratinocyte differentiation by regulating the expression of EDCrelated genes. Conclusion: Oxymatrine can improve erythema, scales, and other clinical symptoms of patients with psoriasis by regulating EDC-related genes and multiple pathways, thereby promoting the repair of epithelial tissue and maintaining the dynamic balance of skin keratosis.