Cover
Vol. 4 No. 1 (2026)

Published: June 1, 2026

Pages: 132-148

Research Article

Evaluation of the Anti-Psoriatic Effect of Topical Dovramilast in an Imiquimod-Induced Psoriasis Mouse Model

Hasnaa Suhail 1 Mohameed Fareed Hameed 1
1 Department of pharmacology, College of pharmacy, Al-Nahrain University, Baghdad, Iraq
History
  • Received: February 5, 2026
  • Revised: March 27, 2026
  • Accepted: April 18, 2026
  • Available Online: June 1, 2026

Abstract

​ Objective: The aim of the study is to determine the pharmacological effect of phosphodiesterase 4 inhibitor (dovramilast) in a psoriasis mice model induced by imiquimod, and to estimate the levels of pro-inflammatory cytokines in skin tissue (IL-17A, IL-23 and TNF-α). Furthermore, histopathological scores for skin tissue were determined. Methods: Fifty BALB/c male albino mice aged 8 weeks were used in this study. The mice were classified into five groups each group contain ten mice (n=10) as the following, group I (control) contained healthy mice, group II (induction) involve application of imiquimod 5% cream once daily for five consecutive days to produce inflammatory lesions that resemble to plaque psoriasis, group III, IV and V involve application of imiquimod 5% cream then three hours later treatments were applied for five consecutive days were, group III received clobetasol 0.05% ointment, group IV received dovramilast 0.3% ointment and group V utilize combination of formula contain both dovramilast 0.15% with clobetasol 0.025% ointment. Results: The dovramilast-treated group showed a significant reduction in all inflammatory cytokines (IL-17A, IL-23 and TNF-α) compared to induction (P<0.05) and not significantly differ from clobetasol effect. Furthermore, dovramilast/clobetasol combination providing significant reduction in all measured inflammatory cytokines (P<0.05) when compared to induction and non-significantly differ from clobetasol-treated group. Conclusions: Topical dovramilast, alone or in combination with clobetasol, may represent a promising therapeutic strategy for the management of psoriasis

Keywords

References

  1. Sugumaran D, Yong ACH, Stanslas J. Advances in psoriasis research: From pathogenesis to therapeutics. Life Sci. 2024;355:122991.
  2. Liu S, He M, Jiang J, Duan X, Chai B, Zhang J, et al. Triggers for the onset and recurrence of psoriasis: a review and update. Cell Commun Signal. 2024;22(1):108.
  3. Wu J, Ma Y, Yang J, Tian Y. Exposure to Air Pollution, Genetic Susceptibility, and Psoriasis Risk in the UK. JAMA Netw Open. 2024;7(7):e2421665.
  4. Lee HJ, Kim M. Challenges and Future Trends in the Treatment of Psoriasis. Int J Mol Sci. 2023;24(17).
  5. Carmona-Rocha E, Rusiñol L, Puig L. New and Emerging Oral/Topical Small-Molecule Treatments for Psoriasis. Pharmaceutics. 2024;16(2).
  6. Bazargani Z, Khorram M, Zomorodian K, Ghahartars M, Omidifar N. Development and comparative analysis of clobetasol-loaded microneedle patches versus clobetasol propionate ointment in experimental induced-psoriasis model. International Journal of Pharmaceutics. 2025;674:125423.
  7. Keerthi C, Sowmya Alahari DSKB, Kr S. Comparison Of Efficacy, Safety And Compliance Of Topical Clobetasol Propionate With Topical Calcipotriol In Chronic Psoriasis–A Prospective Double-Blind Study. International Journal of Medical and Pharmaceutical Research. 2025;6:1154–63.
  8. Milakovic M, Gooderham MJ. Phosphodiesterase-4 Inhibition in Psoriasis. Psoriasis (Auckl). 2021;11:21–9.
  9. Liang X, Zheng J, Huang X, Tan M, Liao J. Apremilast treatment of immune-mediated inflammatory skin diseases: a narrative review. Frontiers in Pharmacology. 2025;16:1633426.
  10. Ghosh N, Reid P, Sparks JA, McCarter K, Ge K, Bass AR. Use of Apremilast for the Treatment of Immune Checkpoint Inhibitor Psoriasis and Psoriatic Arthritis. Arthritis Care & Research. 2025;77(12):1487–92.
  11. Bhuktar H, Thirupataiah B, Mounika G, Samarpita S, Rithvik A, Sasi Priya SVS, et al. Targeting next-generation PDE4 inhibitors in search of potential management of rheumatoid arthritis and psoriasis. Bioorganic Chemistry. 2024;151:107689.
  12. Crowley EL, Gooderham MJ. Phosphodiesterase-4 Inhibition in the Management of Psoriasis. Pharmaceutics. 2023;16(1).
  13. Lusardi M, Rapetti F, Spallarossa A, Brullo C. PDE4D: A Multipurpose Pharmacological Target. International Journal of Molecular Sciences. 2024;25(15):8052.
  14. Subbian S, Tsenova L, Holloway J, Peixoto B, O'Brien P, Dartois V, et al. Adjunctive Phosphodiesterase-4 Inhibitor Therapy Improves Antibiotic Response to Pulmonary Tuberculosis in a Rabbit Model. EBioMedicine. 2016;4:104–14.
  15. Melchiorri D, Rocke T, Alm RA, Cameron AM, Gigante V. Addressing urgent priorities in antibiotic development: insights from WHO 2023 antibacterial clinical pipeline analyses. Lancet Microbe. 2025;6(3):100992.
  16. Boulougoura A, Gabriel E, Laidlaw E, Khetani V, Arakawa K, Higgins J, et al., editors. A phase I, randomized, controlled clinical study of CC-11050 in people living with HIV with suppressed plasma viremia on antiretroviral therapy (APHRODITE). Open Forum Infectious Diseases; 2019: Oxford University Press US.
  17. Hiyama H, Arichika N, Okada M, Koyama N, Tahara T, Haruta J. Pharmacological Profile of Difamilast, a Novel Selective Phosphodiesterase 4 Inhibitor, for Topical Treatment of Atopic Dermatitis. The Journal of Pharmacology and Experimental Therapeutics. 2023;386(1):45–55.
  18. Allen LV, & Ansel, H. C. Ansel’s pharmaceutical dosage forms and drug delivery systems (10th edition): Wolters Kluwer Health business; 2014.
  19. Moos S, Mohebiany AN, Waisman A, Kurschus FC. Imiquimod-Induced Psoriasis in Mice Depends on the IL-17 Signaling of Keratinocytes. J Invest Dermatol. 2019;139(5):1110–7.
  20. Pukale SS, Sharma S, Dalela M, Singh AK, Mohanty S, Mittal A, et al. Multi-component clobetasol-loaded monolithic lipid-polymer hybrid nanoparticles ameliorate imiquimod-induced psoriasis-like skin inflammation in Swiss albino mice. Acta Biomater. 2020;115:393–409.
  21. Khorsheed SM, Abu-Raghif AR, Ridha-Salman H. Alleviative effects of combined topical melatonin and rutin on imiquimod-induced psoriasis mouse model. Pharmacia. 2024;71:1–13.
  22. Verma SK, Lindsay DS, Grigg ME, Dubey JP. Isolation, Culture and Cryopreservation of Sarcocystis species. Curr Protoc Microbiol. 2017;45:20d.1.1–d.1.7.
  23. Bugaut H, Aractingi S. Major Role of the IL17/23 Axis in Psoriasis Supports the Development of New Targeted Therapies. Front Immunol. 2021;12:621956.
  24. Remmele W, Stegner HE. [Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue]. Pathologe. 1987;8(3):138–40.
  25. Papanicolaou P, Chrysomali E, Stylogianni E, Donta C, Vlachodimitropoulos D. Increased TNF-α, IL-6 and decreased IL-1β immunohistochemical expression by the stromal spindle-shaped cells in the central giant cell granuloma of the jaws. Med Oral Patol Oral Cir Bucal. 2012;17(1):e56–62.
  26. Morar, II, Tabăran FA, Mocan T, Jianu EM, Orăsan MS, Pop AD, et al. Immunohistochemical study of psoriatic plaques and perilesional skin in psoriasis vulgaris patients: A pilot study. Exp Ther Med. 2019;18(2):888–94.
  27. Louei Monfared A, Jaafari A, Sheibani MT. Histological and histometrical evidences for phenol immunotoxicity in mice. Comp Clin Path. 2014;23(3):529–34.
  28. Baker BS, Brent L, Valdimarsson H, Powles AV, al-Imara L, Walker M, et al. Is epidermal cell proliferation in psoriatic skin grafts on nude mice driven by T-cell derived cytokines? Br J Dermatol. 1992;126(2):105–10.
  29. Verdonk ML, Cole JC, Hartshorn MJ, Murray CW, Taylor RD. Improved protein-ligand docking using GOLD. Proteins. 2003;52(4):609–23.
  30. Liebeschuetz JW, Cole JC, Korb O. Pose prediction and virtual screening performance of GOLD scoring functions in a standardized test. J Comput Aided Mol Des. 2012;26(6):737–48.
  31. Card GL, England BP, Suzuki Y, Fong D, Powell B, Lee B, et al. Structural basis for the activity of drugs that inhibit phosphodiesterases. Structure. 2004;12(12):2233–47.
  32. Burley Stephen K, Bhatt R, Bhikadiya C, Bi C, Biester A, Biswas P, et al. Updated resources for exploring experimentally-determined PDB structures and Computed Structure Models at the RCSB Protein Data Bank. Nucleic Acids Research. 2024;53(D1):D564–D74.
  33. PerkinElmer Informatics. ChemOffice Professional. 20.0 ed. Waltham, MA: PerkinElmer; 2020.
  34. Dassault Systèmes. BIOVIA Discovery Studio Visualizer. 2021 ed. San Diego: Dassault Systèmes; 2021.
  35. The Cambridge Crystallographic Data Centre. GOLD. 2025.1 ed. Cambridge, UK: The Cambridge Crystallographic Data Centre (CCDC); 2025.
  36. Zhang D, Meng Q, Guo F. Incorporating Water Molecules into Highly Accurate Binding Affinity Prediction for Proteins and Ligands. International Journal of Molecular Sciences. 2024;25(23):12676.
  37. Kitchen DB, Decornez H, Furr JR, Bajorath J. Docking and scoring in virtual screening for drug discovery: methods and applications. Nat Rev Drug Discov. 2004;3(11):935–49.
  38. Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, et al. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem. 2009;30(16):2785–91.
  39. Korb O, Stützle T, Exner TE. Empirical scoring functions for advanced protein-ligand docking with PLANTS. J Chem Inf Model. 2009;49(1):84–96.
  40. Wang L, Liu R, Tang Y, Ma Y, Wang G, Ruan Q, et al. Advances in Psoriasis Research: Decoding Immune Circuits and Developing Novel Therapies. International Journal of Molecular Sciences. 2025;26(18):9233.
  41. Hawkes J, Yan B, Chan T, Krueger J. Discovery of the IL-23/IL-17 Signaling Pathway and the Treatment of Psoriasis. The Journal of Immunology. 2018;201:1605–13.
  42. Chen WC, Wen CH, Wang M, Xiao ZD, Zhang ZZ, Wu CL, et al. IL‐23/IL‐17 immune axis mediates the imiquimod‐induced psoriatic inflammation by activating ACT1/TRAF6/TAK1/NF‐κB pathway in macrophages and keratinocytes. The Kaohsiung Journal of Medical Sciences. 2023;39(8):789–800.
  43. Grine L, Dejager L, Libert C, Vandenbroucke RE. Dual Inhibition of TNFR1 and IFNAR1 in Imiquimod-Induced Psoriasiform Skin Inflammation in Mice. J Immunol. 2015;194(11):5094–102.
  44. Guillaume P, Rupp T, Froget G, Goineau S. Evaluation of Clobetasol and Tacrolimus Treatments in an Imiquimod-Induced Psoriasis Rat Model. Int J Mol Sci. 2024;25(17).
  45. Sun J, Zhao Y, Hu J. Curcumin inhibits imiquimod-induced psoriasis-like inflammation by inhibiting IL-1beta and IL-6 production in mice. PLoS One. 2013;8(6):e67078.
  46. Issa NT, Wang J, Hanly A, Ho M, Obagi S, Damiani G, et al. Structural Insights: What Makes Some PDE4 Inhibitors More Effective in Inflammatory Dermatoses. The Journal of Clinical and Aesthetic Dermatology. 2025;18(7):18.
  47. Issa NT, Wang J, Hanly A, Ho M, Obagi S, Damiani G, et al. Structural Insights: What Makes Some PDE4 Inhibitors More Effective in Inflammatory Dermatoses. J Clin Aesthet Dermatol. 2025;18(7):18–21.
  48. Tavares LP, Negreiros-Lima GL, Lima KM, E Silva PMR, Pinho V, Teixeira MM, et al. Blame the signaling: Role of cAMP for the resolution of inflammation. Pharmacological Research. 2020;159:105030.
  49. Silva-Abreu M, Sosa L, Espinoza LC, Fábrega MJ, Rodríguez-Lagunas MJ, Mallandrich M, et al. Efficacy of Apremilast Gels in Mouse Model of Imiquimod-Induced Psoriasis Skin Inflammation. Pharmaceutics. 2023;15(10).
  50. Krueger G, Faisal S, Dorhoi A. Microenvironments of tuberculous granuloma: advances and opportunities for therapy. Frontiers in Immunology. 2025;Volume 16 - 2025.
  51. Martín-Santiago A, Puig S, Arumi D, Rebollo Laserna FJ. Safety Profile and Tolerability of Topical Phosphodiesterase 4 Inhibitors for the Treatment of Atopic Dermatitis: A Systematic Review and Meta-Analysis. Current Therapeutic Research. 2022;96:100679.
  52. Grundy S, Plumb J, Kaur M, Ray D, Singh D. Additive anti-inflammatory effects of corticosteroids and phosphodiesterase-4 inhibitors in COPD CD8 cells. Respir Res. 2016;17:9.
  53. Jabeen M, Boisgard AS, Danoy A, El Kholti N, Salvi JP, Boulieu R, et al. Advanced Characterization of Imiquimod-Induced Psoriasis-Like Mouse Model. Pharmaceutics. 2020;12(9).
  54. Nair AB, Kumar S, Dalal P, Nagpal C, Dalal S, Rao R, et al. Novel Dermal Delivery Cargos of Clobetasol Propionate: An Update. Pharmaceutics. 2022;14(2).
  55. Guillaume P, Rupp T, Froget G, Goineau S. Evaluation of Clobetasol and Tacrolimus Treatments in an Imiquimod-Induced Psoriasis Rat Model. International Journal of Molecular Sciences. 2024;25(17):9254.
  56. Singh Y, Bagaria A, Bagaria B, Gupta Y. Effect of Oral Drug Apremilast on Histopathological Changes in Patients of Plaque Psoriasis: A Prospective Observational Study. JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH. 2023;17.
  57. Azhar SD, Shahid N, Sadiq A, Khan AW, Sultan Dar M, Fadlalla Ahmed TK. Clobetasol propionate for post-cataract surgery pain and inflammation. Annals of Medicine and Surgery. 2024;86(11):6395–8.
  58. Blauvelt A, Langley RG, Gordon KB, Silverberg JI, Eyerich K, Sommer MOA, et al. Next Generation PDE4 Inhibitors that Selectively Target PDE4B/D Subtypes: A Narrative Review. Dermatol Ther (Heidelb). 2023;13(12):3031–42.
  59. Moussa BA, El-Zaher AA, El-Ashrey MK, Fouad MA. Synthesis and molecular docking of new roflumilast analogues as preferential-selective potent PDE-4B inhibitors with improved pharmacokinetic profile. European Journal of Medicinal Chemistry. 2018;148:477–86.
  60. Jin J, Mazzacuva F, Crocetti L, Giovannoni MP, Cilibrizzi A. PDE4 Inhibitors: Profiling Hits through the Multitude of Structural Classes. International Journal of Molecular Sciences. 2023;24(14):11518.
  61. Kwak HJ, Nam KH. Molecular Properties of Phosphodiesterase 4 and Its Inhibition by Roflumilast and Cilomilast. Molecules. 2025;30(3).
  62. Carmona-Rocha E, Rusiñol L, Puig L. Exploring the Therapeutic Landscape: A Narrative Review on Topical and Oral Phosphodiesterase-4 Inhibitors in Dermatology. Pharmaceutics. 2025;17(1).
  63. Schepers M, Vanmierlo T. Novel insights in phosphodiesterase 4 subtype inhibition to target neuroinflammation and stimulate remyelination. Neural Regeneration Research. 2024;19(3).
  64. Kolb M, Crestani B, Maher TM. Phosphodiesterase 4B inhibition: a potential novel strategy for treating pulmonary fibrosis. European Respiratory Review. 2023;32(167).