The Attenuated Effects of Topical Empagliflozin on Imiquimod-induced Model of Psoriasis in Mice: The attenuated effects of Topical Empagliflozin on Imiquimod-induced Model of Psoriasis in Mice

Alaa H. Abbas; Zahraa H  Abbas; Hayder Ridha Salman; Hayder E Jabar; Abdulkareem H. Abd

doi:10.11594/jtls.14.03.03

Authors

Alaa H. Abbas Al-Nahrain University
Zahraa H Abbas Diwaniyah Health Directorate, Ministry of Health, Iraq
Hayder Ridha Salman Pharmacy Department, Al-Mustaqbal University College, Babylon, Iraq.
Hayder E Jabar College of Pharmacy, Ahl Al-Bayt University, Karbala, Iraq
Abdulkareem H. Abd Department of Pharmacology, College of Medicine, Al-Nahrain University, Baghdad, Iraq.

DOI:

https://doi.org/10.11594/jtls.14.03.03

Keywords:

Empagliflozin, Induced Model of Psoriasis, Inflammation, topical effect, imiquimod-induce

Abstract

Empagliflozin is a sodium-glucose cotransporter inhibitor (SGLT2) that drops blood glucose levels by inhibiting glucose reabsorption and encouraging glucose excretion. Other benefits of empagliflozin include cardiovascular protection, lowering uric acid levels, and reducing liver damage brought on by non-alcoholic fatty liver disease (NAFLD). to investigate the possible influence of two different concentrations of empagliflozin gel on psoriasis induced via imiquimod in mice. dividing 40 mice into five groups (8 mice for each group). All groups gated imiquimod to induce psoriasis (except group I) for seven days. The induction group (Group II) received imiquimod cream for seven days. The rest of the groups gated Clobetasol propionate cream 0.05%, empagliflozin 1% gel, and empagliflozin 3% gel, respectively, once daily for seven days after seven days of induction by imiquimod. The outcomes exhibited that topical empagliflozin had important anti-psoriatic activity by diminishing the Psoriasis Area Severity Index (PASI) score and improving histological alterations during imiquimod application; moreover, it elevated anti-inflammatory biomarker IL-37 and lowered inflammatory biomarkers TNF-α and IL-17. Empagliflozin has substantial anti-psoriatic action against imiquimod-induced psoriasis through its anti-proliferative and anti-inflammatory effects. Also, empagliflozin has a restorative effect on the histopathological alterations of mice's skin induced by imiquimod

Author Biographies

Alaa H. Abbas , Al-Nahrain University

Al-Mustaqbal University, College of Pharmacy, Hillah, Babylon 51001, Iraq
Zahraa H Abbas, Diwaniyah Health Directorate, Ministry of Health, Iraq

Diwaniyah Health Directorate, Ministry of Health, Iraq
Hayder Ridha Salman, Pharmacy Department, Al-Mustaqbal University College, Babylon, Iraq.

Pharmacy Department, Al-Mustaqbal University College, Babylon, Iraq.
Hayder E Jabar, College of Pharmacy, Ahl Al-Bayt University, Karbala, Iraq

College of Pharmacy, Ahl Al-Bayt University, Karbala, Iraq
Abdulkareem H. Abd, Department of Pharmacology, College of Medicine, Al-Nahrain University, Baghdad, Iraq.

Department of Pharmacology, College of Medicine, Al-Nahrain University, Baghdad, Iraq.

References

Davidovici BB, Sattar N, Jörg PC, Puig L et al. (2010) Psoriasis and systemic inflammatory diseases: potential mechanistic links between skin disease and co-morbid conditions. Journal of Investigative Dermatology 130 (7): 1785-1796.‏ doi: 10.1038/jid.2010.103.

Prinz J (2003) The role of T cells in psoriasis. Journal of the European Academy of Dermatology and Venereology 17 (3): 257–270. doi: 10.1046/j.1468-3083.2003.00720.x.

Aijaz SF, Khan SJ, Azim F, Shakeel CS et al. (2022) Deep learning application for effective classification of different types of psoriasis. Journal of Healthcare Engineering 2022.‏ doi: 10.1155/2022/7541583.

Pariser D, Schenkel B, Carter C, Farahi K et al. (2016) A multicenter, non-interventional study to evaluate patient-reported experiences of living with psoriasis. Journal of Dermatological Treatment 27 (1): 19-26.‏ doi: 10.3109/09546634.2015.1044492.

Ridha-Salman H, Al-Zubaidy AA, Abbas AH, Hassan DM, Malik SA (2024) The alleviative effects of canagliflozin on imiquimod-induced mouse model of psoriasis-like inflammation. Naunyn-Schmiedeberg's Archives of Pharmacology 398: 1-21. doi:10.1007/s00210-024-03406-y.

Bachelez H, Van De Kerkhof PC, Strohal R, Kubanov A et al. (2015) Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: a phase 3 randomised non-inferiority trial. The Lancet 386 (9993): 552-561.‏ doi: 10.1016/s0140-6736(14)62113-9.

Choi J, Matoba N, Setoyama D, Watanabe D et al. (2023) The SGLT2 inhibitor empagliflozin improves cardiac energy status via mitochondrial ATP production in diabetic mice. Communications Biology 6 (1): 278.‏ doi: 10.1038/s42003-023-04663-y.

Maayah ZH, Ferdaoussi M, Takahara S, Soni S et al. (2021) Empagliflozin suppresses inflammation and protects against acute septic renal injury. Inflammopharmacology 29: 269-279.‏ doi: 10.1007/s10787-020-00732-4.

Youssef ME, Abd El-Fattah EE, Abdelhamid AM, Eissa H et al. (2021) Interference with the AMPKα/mTOR/NLRP3 signaling and the IL-23/IL-17 axis effectively protects against the dextran sulfate sodium intoxication in rats: a new paradigm in empagliflozin and metformin reprofiling for the management of ulcerative colitis. Frontiers in pharmacology 12: 719984. doi:‏ 10.3389/fphar.2021.719984.

Lee N, Heo YJ, Choi SE, Jeon JY et al. (2021) Anti-inflammatory effects of empagliflozin and gemigliptin on LPS-stimulated macrophage via the IKK/NF-κB, MKK7/JNK, and JAK2/STAT1 signalling pathways. Journal of immunology research 2021.‏ doi: 10.1155/2021/9944880.

Zeng, H, Zhou K, Ye Z (2022) Biology of interleukin 37 and its role in autoimmune diseases (Review). Experimental and Therapeutic Medicine 24 (2): 1–10. doi: 10.3892/etm.2022.11422.

Alam MS, Algahtani MS, Ahmad J, Kohli K et al. (2020) Formulation design and evaluation of aceclofenac nanogel for topical application. Therapeutic Delivery 11 (12): 767-778.‏ doi: 10.4155/tde-2020-0076.

Abbas AH, Abd AH, AbdulRhman S, Abbas IS (2017) The antihyperglycemic and antihyperlipidemic effect of ethanolic extract of Apium graveolens (celery) in Streptozocin/high fat diet induced hyperglycemic mice. karbala journal of pharmaceutical sciences 8 (13): 10-28.‏

Peacock J, Peacock P (2011) Oxford Handbook of Medical Statistics. Oxford University Press.

Jabeen M, Boisgard AS, Danoy A, El Kholti N et al. (2020) Advanced characterization of imiquimod-induced psoriasis-like mouse model. Pharmaceutics 12 (9): 789.‏ doi: 10.3390/pharmaceutics12090789.

Salman H R, Alzubaidy A A, Abbas A H, Mohammad H A (2024) Attenuated effects of topical vinpocetine in an imiquimod-induced mouse model of psoriasis. Journal of Taibah University Medical Sciences 19 (1): 35-53. doi: 10.1016/j.jtumed.2023.09.002.

Li F, Han D, Wang B, Zhang W et al. (2022) Topical treatment of colquhounia root relieves skin inflammation and itch in imiquimod-induced psoriasiform dermatitis in mice. Mediators of Inflammation 2022. doi: 10.1155/2022/5782922.

Jabeen M, Boisgard AS, Danoy A, El Kholti N et al. (2020) Advanced characterization of imiquimod-induced psoriasis-like mouse model. Pharmaceutics 12 (9): 789.‏ doi: 10.1016/j.jid.2018.02.040.

Ridha-Salman H, Shihab EM, Hasan HK, Abbas AH, Khorsheed SM, Ayad Fakhri S (2024) Mitigative Effects of Topical Norfloxacin on an Imiquimod-Induced Murine Model of Psoriasis. ACS Pharmacology & Translational Science 7 (8): 1-16. doi:10.1021/acsptsci.4c00152.

Salman H R, Al-Zubaidy AA, Abbas AH, Zigam QA (2024) The ameliorative effects of topical gemifloxacin alone or in combination with clobetasol propionate on imiquimod-induced model of psoriasis in mice. Naunyn-Schmiedeberg's Archives of Pharmacology 39 (1): 599-616.‏ doi: 10.1007/s00210-023-02629-9.

Abbas AH, Abd AH, Salman HR, Abbas ZH (2023) The Attenuated Effects of Epagliflozin on Imiquimod-Induced Model of Psoriasis in Mice. Latin American Journal of Pharmacy 42: 362-369.‏

Niculet E, Bobeica C, Tatu AL (2020) Glucocorticoid-Induced Skin Atrophy: The Old and the New, Clinical, Cosmetic and Investigational Dermatology 13: 1041. doi: 10.2147/CCID.S224211.

Shabaan MAE, El Balat WM, Abdelrahman A (2021) Combined Topical Vitamin D3 Analogues with Steroid in Treatment of Alopecia Areata. European Journal of Molecular and Clinical Medicine 8 (4): 653-660.

Ritchlin Rendon Gabros S, Nessel TA, Zito PM (2021) Topical Corticosteroids. In: StatPearls. StatPearls Publishing, Treasure Island (F.L.); PMID: 30422535.

Sukhanov S, Higashi Y, Yoshida T, Mummidi S et al. (2021) The SGLT2 inhibitor Empagliflozin attenuates interleukin-17A-induced human aortic smooth muscle cell proliferation and migration by targeting TRAF3IP2/ROS/NLRP3/Caspase-1-dependent IL-1β and IL-18 secretion. Cellular signalling 77: 109825.‏ doi: 10.1016/j.cellsig.2020.109825.

Ahmed S, El-Sayed MM, Kandeil MA, Khalaf MM. (2022) Empagliflozin attenuates neurodegeneration through antioxidant, anti-inflammatory, and modulation of α-synuclein and Parkin levels in rotenone-induced Parkinson’s disease in rats. Saudi Pharmaceutical Journal. 1; 30 (6): 863-73. doi: 10.1016/j.cellsig.2020.109825.

Liu A, Zhao W, Zhang B, Tu Y et al. (2020) Cimifugin ameliorates imiquimod-induced Psoriasis by inhibiting oxidative stress and inflammation via NF-κB/MAPK pathway. Bioscience reports 40 (6): BSR20200471. doi: 10.1042/BSR20200471.

Mshimesh BA (2016) Treatment of Mild to Moderate Plaque Psoriasis with Pimecrolimus, Clobetasol, or Calcipotriol Cream: A comparative study. Journal of the Faculty of Medicine Baghdad. 3; 58 (1):38-45.

Lee N, Heo YJ, Choi S E, Jeon JY et al. (2021) Anti-inflammatory effects of empagliflozin and gemigliptin on LPS-stimulated macrophage via the IKK/NF-κB, MKK7/JNK, and JAK2/STAT1 signalling pathways. Journal of Immunology Research, 2021. doi: 10.1155/2021/9944880.‏

Takeshita J, Grewal S, Langan SM, Mehta NN et al. (2017) Psoriasis and comorbid diseases: epidemiology. Journal of the American Academy of Dermatology 76 (3): 377-390.‏ doi: 10.1016/j.jaad.2016.07.064.

Li B, Tsoi LC, Swindell WR, Gudjonsson JE et al. (2014) Transcriptome analysis of Psoriasis in a large case–control sample: RNA-seq provides insights into disease mechanisms. Journal of Investigative Dermatology 134 (7): 1828-1838.‏ doi: 10.1038/jid.2014.28.

Teng X, Hu Z, Wei X, Wang Z et al. (2014) IL-37 ameliorates the inflammatory process in psoriasis by suppressing proinflammatory cytokine production. The Journal of Immunology 192 (4): 1815-1823.‏ doi: 10.4049/jimmunol.1300047.

Sehat M, Talaei R, Dadgostar E, Nikoueinejad H et al. (2018) Evaluating serum levels of IL-33, IL-36, IL-37 and gene expression of IL-37 in patients with psoriasis vulgaris. Iranian Journal of Allergy, Asthma and Immunology 17 (2): 179-187.‏

Pan Y, Wen X, Hao D, Wang Y et al. (2020). The role of IL-37 in skin and connective tissue diseases. Biomedicine & Pharmacotherapy 122: 109705.‏ doi: 10.1016/j.biopha.2019.109705.

Muhr P, Zeitvogel J, Heitland I, Werfel T et al. (2011). Expression of interleukin (IL)‐1 family members upon stimulation with IL‐17 differs in keratinocytes derived from patients with psoriasis and healthy donors. British Journal of Dermatology 165 (1): 189-193.‏ doi: 10.1111/j.1365-2133.2011.10302.

Khafaji AWM, Al-Zubaidy AA, Iqbal GF, Salman H R (2024) Ameliorative effects of topical ramelteon on imiquimod-induced Ameliorative effects of topical ramelteon on imiquimod-induced psoriasiform inflammation in mice. Naunyn-Schmiedeberg's Archives of Pharmacology, 2024. doi: 10.1007/s00210-024-03017-7.

Ala M, Khoshdel MR, Dehpour AR (2022) Empagliflozin enhances autophagy, mitochondrial biogenesis, and antioxidant defense and ameliorates renal ischemia/reperfusion in nondiabetic rats. Oxidative Medicine and Cellular Longevity 2022. doi: 10.1155/2022/119706

The Attenuated Effects of Topical Empagliflozin on Imiquimod-induced Model of Psoriasis in Mice