Serum Metabolomic Profiling Reveals the Amelioration Effect of Methotrexate on Imiquimod-Induced Psoriasis in Mouse

Abstract

Background: The imiquimod (IMQ)-induced psoriasis mouse model has been used as a model for pathogenic mechanism research, and methotrexate (MTX) is widely employed to treat various clinical manifestations of psoriasis. We explored the underlying pathogenesis of psoriasis and the treatment mechanism of the conventional drugs from the metabolic perspective of the psoriasis mouse model. Methods: Male BALB/c mice were smeared IMQ for 7 days to induce treatment-resistant psoriasis and intragastrically administered 1 mg/kg MTX. We evaluated inflammation of psoriasis-like lesions and therapeutic effects of MTX based on histological changes and immunohistochemistry. Based on gas chromatography-mass spectrometer detection of serum samples, a comprehensive metabolomics analysis was carried out to identify alterations of metabolites. Results: It was found that MTX ameliorated psoriatic lesions (representative erythema, scaling, and thickening) by inhibiting proliferation and differentiation of keratinocytes. Using multivariate statistical analysis to process metabolomics data, the results displayed alterations in serum metabolites among mice of the control group, IMQ group, and MTX group. Compared with group, psoriasis mice had the higher level of d-galactose and lower expression of myo-inositol, 9,12-octadecadienoic acid, and cholesterol. In contrast with the model set, serum levels of glycine, pyrrolidone carboxylic acid, d-galactose, and d-mannose were significantly decreased in the MTX group. Conclusion: The differential metabolites, reflecting the perturbation in the pathways of inositol phosphate metabolism; galactose metabolism; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; and glutathione metabolism, may lead to the pathogenesis of psoriasis, and they are also related to the pharmacological treatment effect of MTX on psoriasis. This study established the foundation for further research on the mechanism and therapeutic targets of psoriasis.

THE EFFECT OF CIPLUKAN EXTRACT (Physalis angulata L.) AS ANTIPSORIATIC AND TO LYMPHOCYTES COUNT OF SKIN TISSUE IN PSORIASIS MICE MODEL

“…The results support research conducted by Luliana in 2017, which stated that ciplukan herbal water extract has anti-inflammatory activity at a dose of 400 mg/kgBW, which also mentioned that the increased dose of ciplukan herbal water extract would increase antiinflammatory effects (Luliana et al, 2017). These results are also in line with Zong's research in 2020, which stated that MTX can improve psoriasis lesions in the form of an erythema, thickening of the skin, and squama in male BALB/c mice when applied to imiquimod (IMQ) for seven days (Zong et al, 2020).…”

Potential mechanism of oral baicalin treating psoriasis via suppressing Wnt signaling pathway and inhibiting Th17/IL‐17 axis by activating PPARγ

“…Finally, PyMOL software was further used to visualize the results of molecular docking. The IMQ-induced psoriasis mouse model was established as described in the previous study (Qin et al, 2014;Zong et al, 2020). 48 mice were randomly divided into 6 groups, with 8 mice in each group.…”

Large-scale plasma-metabolome analysis identifies potential biomarkers of psoriasis and its clinical subtypes

“…PsA is a severe form of arthritis with joint deformities and damage, present in approximately 30 % of patients with psoriasis [4,5]. The crosstalk between genetic and environmental factors (e.g., diet and lifestyle) is responsible for psoriasis by contributing to immunological abnormalities and epidermal proliferation [6]. Large-scale genome-wide association studies in multiple populations have identified approximately 80 genetic loci associated with psoriasis susceptibility [7][8][9][10].…”