Protective effect of cinnarizine on imiquimod-induced mouse model of psoriasis

Year 2025, Volume: 29 Issue: 4, 1783 - 1791, 05.07.2025

Basma Farooq Ali Ahmed Rahma Abu-raghif Hayder Ridha-salman

https://doi.org/10.12991/jrespharm.1734970

Cited By: 1

Abstract

Psoriasis is defined as a series of events. It starts as dermatitis and eventually advances to more extensive inflammation and elevated oxidative stress. The objective of the study is to investigate the possible anti-psoriatic effect of topical cinnarizine on imiquimod-induced psoriasis in mice based on observational, histopathological, and biochemical outcomes. This study included 32 Swiss albino mice who divided into 4 groups (8 for each group) as the following: Group I (control group) was neither induced nor treated and the other three groups were induced for psoriasis by using imiquimod (IMQ) once a day for 6 days and two of these groups subjected to different interventions for eight consecutive days, including topical clobetasol and cinnarizine ointment. All studied groups subjected to Baker and Psoriasis Area Severity Index (PASI) scores assessment in addition to the measurement of interleukin (IL)-17, Tumor Necrosis Factor-alpha (TNF-α), malondialdehyde (MDA), and Ki-67 levels. The result of the study showed that topical cinnarizine significantly reduced the inflammatory signs of the psoriatic lesions, and these findings were supported by the histopathological examination. Additionally, topical cinnarizine significantly decreased IL-17, as well as TNF-α levels. They also reported an important drop in oxidative elements like MDA, and proliferative elements like Ki-67 when compared with the non-treated IMQ-induced psoriatic mice group. It was concluded that topical cinnarizine (3%) ointment demonstrated significant anti-psoriatic activity when compared with induced non-treated group with an effect comparable to that of standard treatment used (clobetasol).

Keywords

Cinnarizine , Clobetasol propionate , Imiquimod-induced psoriasis , Inflammatory skin diseases , Psoriasis

References

• [1] Ali BF, Abu-Raghif AR, Ridha-Salman H, Al-Athari AJH. Vildagliptin topical ointment: an effective treatment for imiquimod-induced psoriasis in mice. https://doi.org/10.1007/s10735-025-10416-4
• [2] Journal of Molecular Histology. 2025;56(3):143. Wang Q, Yan D, Zheng S, Li M, Li J, Fu X, Fu D, Hu H, Song X, Tian Z. Cytokine Profiles and the relationship of disease severity in patients with psoriasis. Indian J Dermatol. 2022;67(2):204. https://doi.org/10.4103/ijd.ijd_79_22
• [3] Raghif ARA, Yaseen YA, Dawood MH. Effects of Coenzyme Q10 administration on glucose homeostasis parameters in prediabetic patients. Int J Pharm Sci Res. 2017;9(11):2274-2277.
• [4] Abbas AH, Abbood MS, Ridha-Salman H, Fakhri SA, Abbas ZH, Al-Athari AJH. Suppressive effect of topical moxifloxacin on imiquimod-induced model of psoriasis in mice. Naunyn Schmiedebergs Arch Pharmacol. 2025. https://doi.org/10.1007/s00210-025-04317-2
• [5] Khafaji AWM, Al-Zubaidy AAK, Farhood IG, Salman HR. Ameliorative effects of topical ramelteon on imiquimod induced psoriasiform inflammation in mice. Naunyn Schmiedebergs Arch Pharmacol. 2024:1-18. https://doi.org/10.1007/s00210-024-03017-7
• [6] Manna MJ, Abu-Raghif A, Abbood MS. Effect of captopril on inflammatory biomarkers, oxidative stress parameters and histological outcome in experimental induced colitis. J Pharm Sci Res. 2017;9(9):1629.
• [7] Manna MJ, Abu-raghif A, Muhsin HY. The effect of Niclosamide in acetic acid induce colitis: an experimental study. Prensa Méd Argent. 2019; 105(5):309-316.
• [8] Habbas AH, Abu-Raghif AR, Ridha-Salman H, Hussein MN. Therapeutic effect of bosentan on 2, 4 dinitrochlorobenzene (DNCB)-induced atopic dermatitis mouse model. Arch Dermatol Res. 2025;317(1):436. https://doi.org/10.1007/s00403-025-03955-z
• [9] Aal-Aaboda M, Abu Raghif AR, Hadi NR. Effect of lipopolysaccharide from Rhodobacter sphaeroides on inflammatory pathway and oxidative stress in renal ischemia/reperfusion injury in male rats. Arch Razi Inst. 2021;76(4):1013-1024. https://doi.org/10.22092%2Fari.2021.356003.1761
• [10] Aal-Aaboda M, Abu Raghif A, Hadi N. Renoprotective potential of the ultra-pure lipopolysaccharide from Rhodobacter Sphaeroides on acutely injured kidneys in an animal model. Arch Razi Inst. 2021;76(6):1755-1764. https://doi.org/10.22092/ari.2021.356202.1803
• [11] Khairutdinov VR, Mikhailichenko AF, Belousova IE, Kuligina ES, Samtsov AV, Imyanitov EN. The role of intradermal proliferation of T-cells in the pathogenesis of psoriasis. An Bras Dermatol. 2017;92(1):41-44. https://doi.org/10.1590/abd1806-4841.20175765
• [12] Abu-Raghif AR, Qasim BJ, Abady AH, Sahib HB. Effects of aqueous thyme extract against cisplatin induced nephrotoxicity in rabbits. Int J Pharm Sci Rev Res. 2015;30(1):190-194.
• [13] Nidhal Ghazy D, Rahmah Abu-Raghif A. Effects of apremilast on ınduced hypertrophic scar of rabbits. Arch Razi Inst. 2021;76(6):1803-1813. https://doi.org/10.22092%2FARI.2021.356195.1800
• [14] Schön MP, Wilsmann-Theis D. Current developments and perspectives in psoriasis. J Dtsch Dermatol Ges. 2023;21(4):363-372. https://doi.org/10.1111/ddg.15033
• [15] Brownstone ND, Hong J, Mosca M, Hadeler E, Liao W, Bhutani T, Koo J. Biologic Treatments of Psoriasis: An Update for the Clinician. Biologics. 2021;15:39-51. https://doi.org/10.2147/btt.s252578
• [16] Plescia F, Salvago P, Dispenza F, Messina G, Cannizzaro E, Martines F. Efficacy and pharmacological appropriateness of cinnarizine and dimenhydrinate in the treatment of vertigo and related symptoms. Int J Environ Res Public Health. 2021;18(9):4787. https://doi.org/10.3390/ijerph18094787
• [17] Blazsó G, Rázga Z, Gábor M. Effects of cinnarizine on different experimentally induced oedemas. Fundam Clin Pharmacol. 1999;13(1):91-95. https://doi.org/10.1111/j.1472-8206.1999.tb00325.x
• [18] Abdel-Fattah MM, Messiha BAS, Salama AAA. Assessment of the mechanistic role of cinnarizine in modulating experimentally-induced bronchial https://doi.org/10.1159/000438705
• [19] Chang TS, Lin VC. Melanogenesis inhibitory activity of two generic drugs: cinnarizine and trazodone in mouse B16 melanoma cells. Int J Mol Sci. 2011;12(12):8787-8796. https://doi.org/10.3390/ijms12128787
• [20] Omar M, Salam A, Siham M E, Nermeen M S. In vivo effect of cinnarizine on acute hepatic damage in mice. Bull Natl Res Cent. 2007; 32 (4): 393-404.
• [21] Rego EM, Corrado AP, Prado WA. Antinociceptive effects of calcium channel blockers in the rat. Braz J Med Biol Res. 1990;23(3-4):297-305.
• [22] Del Pozo E, Caro G, Baeyens J. Analgesic effects of several calcium channel blockers in mice. Eur J Pharmacol. 1987;137(2-3):155-160. https://doi.org/10.1016/0014-2999(87)90216-0
• [23] Miranda H, Pelissier T, Sierralta F. Analgesic effects of intracerebroventricular administration of calcium channel blockers in mice. Gen Pharmacol. 1993;24(1):201-204. https://doi.org/10.1016/0306-3623(93)90035-v
• [24] Lozeva V, Marazova K, Belcheva A. Gastric histamine content and ulcer formation in rats with ethanol-induced injury. Effects of cinnarizine and flunarizine. Agents Actions. 1994;41(1):C91-C92. https://doi.org/10.1007/bf02007781
• [25] Abdel-Salam OM, El-Sayed El-Shamarka M, Salem NA, El-Mosallamy AE, Sleem AA. Amelioration of the haloperidol-induced memory impairment and brain oxidative stress by cinnarizine. EXCLI J. 2012;11:517-530.
• [26] Medovic MV, Jakovljevic VL, Zivkovic VI, Jeremic NS, Jeremic JN, Bolevich SB, Ravic Nikolic AB, Milicic VM, Srejovic IM. Psoriasis between autoimmunity and oxidative stress: Changes ınduced by different therapeutic approaches. Oxid Med Cell Longev. 2022;2022:2249834. https://doi.org/10.1155/2022/2249834
• [27] Mahdi ZA, Hussain AM, Alblesh HA. Histopathological and immunological effects of nebivolol 5% topical cream in mice model of imiquimod-induced psoriasis. Rafidain J Med Sci. 2024;6(1):133-141. https://doi.org/10.54133/ajms.v6i1.527
• [28] Sylviningrum T, Wasita B, Purwanto B, Kariosentono H, Soetrisno S. Indonesian Ciplukan extract inhibited TGF β1/NF-κB pathway in experimental psoriasis mouse models. Open Access Maced J Med Sci. 2022;10(A):938-946. http://dx.doi.org/10.3889/oamjms.2022.9913
• [29] Khafaji AWM, Al-Zubaidy AAK, Farhood IG, Salman HR. Ameliorative effects of topical ramelteon on imiquimod induced psoriasiform inflammation in mice. Naunyn Schmiedebergs Arch Pharmacol. 2024;397(8):6231-6248. https://doi.org/10.1007/s00210-024-03017-7
• [30] Salman HR, Alzubaidy AA, Abbas AH, Mohammad HA. Attenuated effects of topical vinpocetine in an imiquimod-induced mouse model of psoriasis. J Taibah Univ Med Sci. 2023;19(1):35-53. https://doi.org/10.1016%2Fj.jtumed.2023.09.002
• [31] Al-juhaishi AMR, Al-Zubaidy AAK, Al-Mousawy JMM. Effects of montelukast on imiquimod-induced model of psoriasis In mice. Nat Vol Essent Oil. 2021;8(6):3160-3171.
• [32] Salman HR, Al-Zubaidy AA, Abbas AH, Zigam QA. The ameliorative effects of topical gemifloxacin alone or in combination with clobetasol propionate on imiquimod-induced model of psoriasis in mice. Naunyn Schmiedebergs Arch Pharmacol. 2024;397(1):599-616. https://doi.org/10.1007/s00210-023-02629-9
• [33] Mohammed SS, Mustafa WW. Effects of lycopene as monotherapy or combined with clobetasol on spleen index and inflammatory markers in mouse model of imiquimod-induced psoriasis. Rafidain J Med Sci. 2023;4:86-91. https://doi.org/10.54133/ajms.v4i.118
• [34] Del Rosso JQ. Topical corticosteroid therapy for psoriasis-A review of clobetasol propionate 0.025% cream and the clinical relevance of penetration modification. J Clin Aesthet Dermatol. 2020;13(2):22-29.
• [35] Sidgiddi S, Naqvi SMH, Shenoy M, Balraj DN, Kothari J, Gupta S, Haq R, Mittal R, Mehta S, Mane A. Efficacy and safety of novel formulation of clobetasol propionate 0.025% cream in indian moderate-to-severe psoriasis patients: Phase-2a, randomized 3-arm study. Dermatol Ther (Heidelb). 2021;11(5):1717-1732. https://doi.org/10.1007/s13555-021-00591-z
• [36] Atarbashe RK, Abu-Raghif A. Comparative treatment of induced ulcerative colitis in male rat model by using cinnarizine and sulfasalazine. Iraqi J Vet Sci. 2020;34(2):465-472. http://dx.doi.org/10.33899/ijvs.2019.126170.1254
• [37] Hsieh CY, Tsai TF. Use of H-1 antihistamine in dermatology: More than ıtch and urticaria control: A systematic review. Dermatol Ther (Heidelb). 2021;11(3):719-732. https://doi.org/10.1007/s13555-021-00524-w
• [38] Checa J, Aran JM. Airway redox homeostasis and ınflammation gone awry: From molecular pathogenesis to emerging therapeutics in respiratory pathology. Int J Mol Sci. 2020;21(23):9317. https://doi.org/10.3390/ijms21239317
• [39] Abdel-Salam OM. Modulation of visceral nociception, inflammation and gastric mucosal injury by cinnarizine. Drug Target Insights. 2007;2:29-38.
• [40] Aukunuru J, Bonepally C, Guduri G. Preparation, characterization and optimization of ibuprofen ointment intended for topical and systemic delivery. Trop J Pharm Res. 2007;6(4):855-860. http://dx.doi.org/10.4314/tjpr.v6i4.14670
• [41] van der Fits L, Mourits S, Voerman JS, Kant M, Boon L, Laman JD, Cornelissen F, Mus AM, Florencia E, Prens EP, Lubberts E. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J Immunol. 2009;182(9):5836-5845. https://doi.org/10.4049/jimmunol.0802999
• [42] Fredriksson T, Pettersson U. Oral treatment of pustulosis palmo-plantaris with a new retinoid, Ro 10-9359. Dermatologica. 1979;158(1):60-64. https://doi.org/10.1159/000250744
• [43] Pierozan P, Jernerén F, Ransome Y, Karlsson O. The choice of euthanasia method affects metabolic serum biomarkers. Basic Clin Pharmacol Toxicol. 2017;121(2):113-118. https://doi.org/10.1111/bcpt.12774
• [44] Mekkey SM, Abu Raghif AR, Ridha Alkafaji HA, Hadi NR. The anti-Parkinson effects of Liraglutide in rat model of Rotenone induced Parkinsonism. Int J Pharm Res. 2020;12(S2):3695-3706. http://dx.doi.org/10.31838/ijpr/2020.SP2.449
• [45] Thammer MR, Sahib HB, Ridha-Salman H. Skin Healing Potential of Bioactive Components From Lycoperdon lividum Mushroom Versus β-Sitosterol in Rat Model of Burn Wounds. Microsc Res Tech. 2025. https://doi.org/10.1002/jemt.24864
• [46] Ali KH, Al-Jawad FH, Kadhim HM, Al-Dabagh MA. The possible hepatoprotective effects of combination of an oral krill oil and silymarin against carbon tetrachloride (Ccl4)-induced liver fibrosis/ injury in white albino rats: Histopathological, and biochemical studies. Int J Drug Deliv Technol. 2021;11(3):827-833. http://dx.doi.org/10.25258/ijddt.11.3.29
• [47] Yahiya YI, Hadi NR, Abu Raghif A, Al Habooby NGS. Protective effect of IAXO-102 on renal ischemia-reperfusion injury in rats. J Med Life. 2023;16(4):623-630. https://doi.org/10.25122/jml-2022-0280
• [48] Raheem AK, Abu RAR, Zigam QA. Cilostazol protects against sepsis-induced kidney impairment in a mice model. J Med Chem Sci. 2023, 6(5) 1193-1203. https://doi.org/10.26655/JMCHEMSCI.2023.5.25
• [49] Baker BS, Fry L. The immunology of psoriasis. Br J Dermatol. 1992;126(1):1-9. https://doi.org/10.1111/j.1365 2133.1992.tb08394.x
• [50] Raheem AK, Abu-Raghif AR, Abbas AH, Ridha-Salman H, Oubaid EN. Quercetin mitigates sepsis-induced renal injury via inhibiting inflammatory and oxidative pathways in mice. Journal of Molecular Histology. 2025;56(3):184. https://doi.org/10.1007/s10735-025-10442-2
• [51] Yahiya YI, Hadi NR, Abu Raghif A, Qassam H, Al Habooby NGS. Role of Iberin as an anti-apoptotic agent on renal ischemia-reperfusion injury in rats. J Med Life. 2023;16(6):915-919. https://doi.org/10.25122/jml-2022-0281
• [52] Hussein ZA, Abu-Raghif AR, Tahseen NJ, Rashed KA, Shaker NS, Fawzi HA. Vinpocetine alleviated alveolar epithelial cells injury in experimental pulmonary fibrosis by targeting PPAR-γ/NLRP3/NF-κB and TGF β1/Smad2/3 pathways. Sci Rep. 2024;14(1):11131. https://doi.org/10.1038/s41598-024-61269-y
• [53] Hussein ZA, Abu-Raghif AR, Fawzi HA. The mitigating effect of para-hydroxycinnamic acid in bleomycin-induced pulmonary fibrosis in mice through targeting oxidative, inflammatory and fibrotic pathways. Basic Clin Pharmacol Toxicol. 2024;135(1):23-42. https://doi.org/10.1111/bcpt.14018
• [54] Aldafaay AA, Amir HAA, Abdulhussain HA, Badry AS, Abdulsada AK. The use of Urinary α-amylase level in a diagnosis of Chronic renal failure. Res J Pharm Technol. 2021;14(3):1597-1600. http://dx.doi.org/10.5958/0974 360X.2021.00283.3
• [55] Abdulamir HA, Aldafaay AA, Al-Shammari AH. the role of liver function tests in monitoring the effect of enzyme replacement therapy in children with Gaucher Disease. Res J Pharm Technol. 2022;15(8):3490-3496. https://doi.org/10.52711/0974-360X.2022.00585