@Article{
AUTHOR = {Bari, Mohammed Abdul Muttalib Abdul Bari},
TITLE = {Evaluation of Topical Methotrexate in an Imiquimod-Induced Mouse Model of Psoriasis: Comparative Study with Clobetasol and Tacrolimus},
JOURNAL = {Journal of Experimental Pharmacology and Toxicology},
VOLUME = {4},
YEAR = {2026},
NUMBER = {1},
PAGES = {0--0},
URL = {https://j-pharmacol-tox-exp.com/article/4/1/26},
ISSN = {3091-0595},
ABSTRACT = {Background: Psoriasis is an immune-mediated skin disorder marked by abnormal keratinocyte proliferation and immune cell infiltration, with dysregulated cytokines such as TNF-α, IL-6, and IL-17. Methotrexate (MTX) is an established systemic therapy for moderate to severe psoriasis; however, the efficacy of topical MTX remains uncertain and requires further evaluation in controlled studies. Purpose: This study evaluated a 1% topical MTX formulation in an imiquimod-induced mouse model of psoriasis and compared its effects with topical clobetasol propionate (0.05%) and tacrolimus (0.1%). In addition, in silico molecular docking was performed as an exploratory complement to the clinical and histological assessments; docking results are hypothesis-generating and do not demonstrate direct in vivo mechanisms. The study did not include a systemic MTX arm. Methods: Male C57BL/6 mice were randomized into five groups (negative control, IMQ positive control, clobetasol, tacrolimus, and MTX 1%). Psoriasis-like dermatitis was induced with topical 5% imiquimod for 7 days, followed by twice-daily topical treatment for 14 days. Clinical severity was scored using a murine PASI scale; skin samples were collected for histopathology and for measurement of TNF-α and IL-6 by ELISA. In silico docking against TNF-α and IL-6 was performed using AutoDock Vina; docking is reported as exploratory. Results: Topical MTX produced marked reductions in PASI scores and improved histological architecture compared with IMQ controls, with effects comparable to clobetasol and greater than tacrolimus in this model. MTX-treated skin showed lower TNF-α and IL-6 levels (expressed as pg/mg protein, Docking simulations confirmed moderate predicted binding affinities of MTX, clobetasol, and tacrolimus to TNF-α and IL-6; these findings are presented as exploratory and hypothesis-generating, and do not constitute proof of direct cytokine binding in vivo. Conclusion: In this imiquimod mouse model, a 1% topical MTX formulation demonstrated significant anti-inflammatory and antiproliferative effects, comparable to topical clobetasol and superior to tacrolimus under the conditions tested. These results support further pharmacokinetic, skin penetration, and safety studies to confirm local bioavailability and to evaluate systemic exposure before clinical translation.},
DOI = {10.6425/042026jept005}
}