Evaluation of Antipsoriatic Effect of Ivermectin in Animal model of Psoriasis

Authors

  • Ahmed Salim Mahmood College of Pharmacy, Al-Ameen University College, Baghdad, Iraq
  • Zeena Ayad Hussein Department of Pharmacology, College of Medicine, Al-Nahrain University, Baghdad, Iraq.
  • Nabaa Mohammed Ibrahim Department of Pharmacognosy, College of Pharmacy, University of Baghdad, Baghdad, Iraq.

DOI:

https://doi.org/10.31351/vol34iss4pp76-84

Keywords:

IL-17, Imiquimod induce psoriasis, Ivermectine, Psoriasis and VEGF

Abstract

Ivermectin (IVR) is widely used for the treatment of onchocerciasis and other nematode infections .Recent studies have reported that IVR has an anti-inflammatory effect and is used in the treatment of allergic asthma, dermatitis, and arthritis. Psoriasis is a chronic immune-mediated inflammatory skin disease in which IL-17 and VEGF play an important role as pro-inflammatory and angiogenic mediators.To evaluate the therapeutic effect of IVR in psoriasis, we used an imiquimod (IMQ)-induced psoriasis model in rats. Twenty-four male wister-albino rats, age 3-4 monthe and weighing 170-200 g were used in this experiment. They were assigned at random into four groups, each group include 6 animals. Rats in each group (except normal control group) are topically administered 62.5 mg of IMQ cream for 10 days, then  they were treated for 12 days with one of the following drugs starting from the day four after first application of IMQ cream: the first group treated with subcutaneous (SC) injection of normal saline once daily and consider as positive control group; the second one is Methotrexate (MTX) treated group using conventional dose in autoimmune disease (1.0 mg/kg/week, intraperitoneal injection); and last group is IVR treated group (0.5 mg/kg/day, SC injection). Subcutaneous administration of IVR to the rats, significantly minimize the Psoriasis Area Severity index (PASI) regarding the thickness, scaling and erythema (3.00 ± 2.19) comparing to the positive control group (6.83 ± 1.16) with p value < 0.05. Furthermore, IVR attenuate the histopathological changes of  skin lesion with no significant differences comparing to MTX treated group (standard drug for psoriasis treatment). In addition to that, the level of IL-17 and VEGF in psoriatic skin lesion were significantly reduced by  IVR  and MTX compared to a positive control group (p < 0.05), suggesting the ability of this drug in the alleviation of psoriasis by this mechanism.

How to Cite

1.
Salim Mahmood A, Zeena Ayad Hussein, Nabaa Mohammed Ibrahim. Evaluation of Antipsoriatic Effect of Ivermectin in Animal model of Psoriasis. Iraqi Journal of Pharmaceutical Sciences [Internet]. 2025 Dec. 20 [cited 2025 Dec. 21];34(4):76-84. Available from: https://www.bijps.uobaghdad.edu.iq/index.php/bijps/article/view/3566

Publication Dates

Received

2024-03-27

Revised

2024-04-25

Accepted

2024-09-01

Published Online First

2025-12-20

References

Bu J, Ding R, Zhou L, Chen X, Shen E. Epidemiology of psoriasis and comorbid diseases: A narrative review. Frontiers in Immunology. 2022;13(6):1–19. https:// doi. org /10.3389/fimmu.2022.880201.

Psoriasis C, Branch D, Association CM. Guidelines for the diagnosis and treatment of psoriasis in China. International Journal of Dermatology and Venereology. 2022; 3(1) :14–26. https:// doi. org/ 10. 1097 /JD9 .000 0000000000074.

Armstrong AW, Read C. Pathophysiology, clinical presentation, and treatment of psoriasis: A review. JAMA - Journal of the American Medical Association. 2020;323(19):1945–60. https://doi.org/10.1001/jama.2020.4006.

Armstrong AW, Robertson AD, Wu J, Schupp C, Lebwohl MG. Undertreatment, treatment trends, and treatment dissatisfaction among patients with psoriasis and psoriatic arthritis in the United States: Findings from the National Psoriasis Foundation Surveys, 2003-2011. JAMA Dermatology. 2013;149(10):1180–5. http://doi.org/10.1001/jamadermatol.2013.5264.

Salem RM. Methotrexate mechanism of action in plaque psoriasis. Journal of Clinical and Aesthetic Dermatology. 2022;15(8):42–6.

Mazhar F, Krantz Å, Schain L, Lysell J, Carrero JJ. Occurrence of adverse events associated with the initiation of methotrexate and biologics for the treatment of psoriasis in routine clinical practice. Journal of Dermatological Treatment. 2023;34(1):1–10. https:// doi. org/ 10. 1080 /09546634.2023.2215354.

DiNicolantonio JJ, Barroso-Aranda J, McCarty M. Ivermectin may be a clinically useful anti-inflammatory agent for late-stage COVID-19. Open Heart. 2020;7(2): e001350. https:// doi. org/10.1136%2Fopenhrt-2020-001350corr1.

Ci X, Li H, Yu Q, Zhang, X, Yu L, Chen N, Song Y, Deng. Ivermectin exerts an anti-inflammatory effect by downregulating the nuclear transcription factor kappa-B and mitogen-activated protein kinase activation pathway. Fundamental & clinical pharmacology.2009; 23 (4):449–455.https: //doi.org/10.1111/j.1472-8206.2009.00684.x.

Zhang X, Song Y, Ci X, An N, Ju Y, Li H. Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice. Inflammation Research. 2008;57: 524–529. https:// doi. org/ 10.1007/s00011-008-8007-8.

Yan S, Ci X, Na C, Chen C, Li X, Chu X. Anti-inflammatory effects of ivermectin in a mouse model of allergic asthma. Inflammation Research. 2011; 60:589–596.https:/ /doi. org /10.1007/s00011-011-0307-8.

Mosca M, Hong J, Hiedler E, Hakimi M, Liao W, Bhutani T. The role of IL-17 cytokines in psoriasis. Immunotargets and Therapy. 2021; 10:409-418.https: //doi. org/ 10. 21 47/ ITT .S 2 40891.

Luengas-Martinez A, Hardman-Smart J, Paus R, Young HS. Vascular endothelial growth factor as a promising therapeutic target for the management of psoriasis. Experimental Dermatology. 2020;29(8): 687-698.https: //doi. org/10.1111/exd.14151.

Wang, Yuhei, Wang H, Chasuna, Bagenna. Astilbin reduces ROS accumulation and VEGF expression through Nrf2 in psoriasis-like skin disease. Biological Research. 2019; 52:1–8. http://dx.doi.org/10.1186/s40659-019-0255-2.

Parmar KM, Jagtap CS, Katare NT, Dhobi M, Prasad SK. Development of a psoriatic-like skin inflammation rat model using imiquimod as an inducing agent. Indian Journal of Pharmacology.2021;53(2): 125-131. https: //doi .org/10.4103/ijp.IJP-506-19.

El-Sheikh SM, El-Alim AE. -A. F, Galal AA, El-Sayed RG, El-Naseery NI. Anti-arthritic effect of β-caryophyllene and its ameliorative role on methotrexate and/or leflunomide-induced side effects in arthritic rats. Life Science. 2019; 233:116750. https:// doi. org/ 10. 1016/j.lfs.2019.116750.

El-Sawy AESF, El-Maddawy ZK, Seed SA. Adverse effects of ivermectin in comparison with rafoxanide on male rats, Alexandria Journal for Veterinary Sciences. 2015; 47:119-128.https://doi.org/10.5455/ajvs.198997.

Horváth S, Komlódi R, Perkecz A, Pintér E, Gyulai R Kemény Á. Methodological refinement of aldara-induced psoriasiform dermatitis model in mice. Scientific Reports.2019;9:3685. https:// doi. org /10. 1038 /s41598-019-39903-x.

Omar NI, Bahrain B, Lau SF, Ibrahim N, Mohd N, Fauzi AA, Muhammad N, Fernandez NM.The influence of ficus deltoidea in preserving alveolar bone in ovariectomized rats. Veterinary Medicine International. 2020; 2020:8862489.https://doi.org/10.1155/2020/8862489.

Zhang S, Liu X, Meil L, Wang H, Fang F, Epigallocatechin-3-gallate (EGCG) inhibits imiquimod-induced psoriasis-like inflammation of BALB/c mice.BMC Complementary and Alternative Medicine. 2016; 16:1-11.https://doi.org/10.1186/s12906-016-1325-4.

Ventre E, Rozières A, Lenief V, Albert F, Rossio P, Laoubi L, et al.Topical ivermectin improves allergic skin inflammation. Allergy. 2017;72(8):1212-1221.https:// doi.org /10. 11 1 1/all.13118.

Khan MUA, Akhtar T, Naseem N, Aftab U, Hussain S, Shahzad M. Evaluation of the therapeutic potential of ivermectin against complete Freund's adjuvant-induced arthritis in rats: Involvement of inflammatory mediators. Fundamental and Clinical Pharmacology, 2023; 37(5):971-982.https: //doi .org /10 .1 111 /fcp . 12902.

Schaller M, Gonser L, Belge K, Braunsdorf C, Nordin R, Scheu A, Borelli C.Dual anti-inflammatory and anti-parasitic action of topical ivermectin 1% in papulopustular rosacea. Journal of the European Academy of Dermatology and Venereology, 2017;31(11):1907-1911.https: //doi. org /10 .11 11/jdv.14437.

Dogra S, Mahajan R. Psoriasis: Epidemiology, clinical features, co-morbidities, and clinical scoring. Indian Dermatology Online Journal, 2016; 7(6):471-480. https :// doi .org /10 .41 0 3 /2229-5178.193906.

Rendon A, Schäkel Psoriasis pathogenesis and treatment. International Journal of Molecular Science.2019; 20(6) :1475 .https: // doi .org /10 .3390/ijms20061475.

Rapalli VK, Waghule T, Gorantla S, Dubey SK, Saha RN, Singhvi G. Psoriasis: pathological mechanisms, current pharmacological therapies, and emerging drug delivery systems. Drug Discovery Today, 2020; 25(12): 2212-2226.https://doi.org/10.1016/j.drudis.2020.09.023.

Hansel A, Gunther C, Ingwersen J.Human slan (6-sulfo LacNAc) dendritic cells are inflammatory dermal dendritic cells in psoriasis and drive strong T(h)17/T(h)1 T-cell response. Journal of Allergy and Clinical Immunology. 2011; 27(3):787-794.https: //doi. org /10. 101 6/ j.jaci.2010.12.009.

Krueger JG, Brunner PM. Interleukin-17 alters the biology of many cell types involved in the genesis of psoriasis, systemic inflammation, and associated comorbidities. Experimental Dermatology. 2018; 27(2):115-123.https: // doi .org/10.1111/exd.13467.

Tollenaere MAX, Hebsgaard J, Ewald DA, Lovato P, Garcet S, Li X, et al. Signaling of multiple interleukin (IL)-17 family cytokines via IL-17 receptor drives psoriasis-related inflammatory pathways. British Journal of Dermatology. 2021;185(3):585–594.https:// doi . org/10.1111/bjd.20090.

Martin DA, Towne JE, Kricorian G, Klekotka P, Gudjonsson JE, Krueger JG, Russell CB. The emerging role of interleukin-17 in the pathogenesis of psoriasis: preclinical and clinical findings. Journal of Investigative Dermatology, 2013;133(1):17–26.https :// doi .org/10.1038/jid.2012.

Patil D, Tharayil KS, Arakali LSh. Relevance of serum vascular endothelial growth factor (VEGF) and serum interleukin-10 in the severity of psoriasis in South Indian patients: A case-control study. Turkish Journal of Dermatology. 2023; 17(1): 6-10.https: // do. Org/10.4103/tjd.tjd_46_22

Zhan H, Li H, Liu C, Cheng, L, Yan S, Li Y. Association of circulating vascular endothelial growth factor levels with autoimmune diseases: A systematic review and meta-analysis, Frontiers in Immunology.2021;12:1664-3224.https://doi.org/10.3389/fimmu.2021.674343.

Shehata W, Shoeib M, Swan A, El-Nidany S. Association of vascular endothelial growth factor gene polymorphism with psoriasis. Menoufia Medical Journal. 2021; 34(3): 884-889.‏https://doi.org/10.4103/mmj.mmj_20_20.

Agnieszka G, Mateusz S, Aldona P, Tomasz Z, Dorota K. The role of VEGF in psoriasis: an update.Acta Angiologica. 2018; 24(4):134-140.https://doi.org/10.5603/AA.2018.0019.

Branisteanu DE, Nicolescu AC, Branisteanu DC, Branisteanu CI, Dragoi AC, Bogdanici CM, et al. Cardiovascular comorbidities in psoriasis (review). Experimental and Therapeutic Medicine, 2022; 23(2):1-5. https://doi.org/10.3892/etm.2021.11075.

Honma M, Nozaki H. Molecular pathogenesis of psoriasis and biomarkers reflecting disease Activity. Journal of Clinical Medicine, 2021;10 (15):3199.https://doi.org/10.3390/jcm10153199.

D’Amico F, Skarmoutsou E, Granata M, Trovato C, Rossi GA, Mazzarino MC. S100A7: A rAMPing up AMP molecule in psoriasis. Cytokine & growth factor reviews, 2016; 32:97–10 https:// doi. org /10 .10 16 /j .c y to gfr .2016.01.002.

Downloads

Published

2025-12-20

Issue

Section

Article