Effect of Aescin in Psoriatic-Induced Animal Model: Immunohistochemical and Pathological Study

Rafal wadhah; Basma  Talib; Ghaith ali; Wamidh H Talib

doi:10.32947/ajps.v24i1.1035

Authors

Rafal wadhah Department of Pharmacology and Toxicology, College of Pharmacy, Mustansiriyah University, Iraq.
Basma Talib Department of Pharmacology and Toxicology, College of Pharmacy, Mustansiriyah University, Iraq.
Ghaith ali Department of Pharmacology and Toxicology, College of Pharmacy, Al-Bayan University, Iraq
Wamidh H Talib Department of clinical pharmacy and theraputics, applied science university, amman , Jorden

DOI:

https://doi.org/10.32947/ajps.v24i1.1035

Keywords:

Psoriasis, Imiquimod, Aescin, Clobetasol, Ki-67, TNF-α

Abstract

Background: Aescin is a mixture of the triterpene saponins extracted from the seeds of the horse chestnut tree Aesculus hippocastanum. Aescin has a venotonic, anti-inflammatory, antioxidant and anti-edematous characteristics that are mostly connected to the agent molecular mechanism.

Objective: The present study aim to investigate the potential effects of Aescin on psoriasis induced by Imiquimod in male rats, ncluding its effect on the level of tumor necrosis factor alpha, Ki-67 and the histopathologic features of the psoriatic skin.

Methods: Thirty-six albino male rats were divided into six groups each group containing 6 animals, psoriasis was induced by Imiquimod to five of the groups, while for the last group vasaline was applied and the group served as a control group. The animals were then treated with topical Aescin, topical clobetasol, combination of topical Aescin and clobetasol and oral Aescin, finally all animals were sacrificed and the dorsal back skin was taken to perform histopathological and immunohistochemical analysis.

Results: regarding the level of Ki-67, Strong expression of Ki-67 was seen in the group who received Imiquimod only, where the scoring of Ki-67 was notably lowered among the other groups. However, the lowest expression was noticed in the group that were treated with the combination of topical Aescin and clobetasol. While the number of TNF-α positive cells and the intensity of immunostaining were higher in the induction group who received Imiquimod only and the lowest among the group who received the combination of topical Aescin and Clobetasol. Lastly the histopathologic analysis shows that the histopathologic features of psoriasis was markedly affected by the anti-inflammatory effect of Aescin and clobetasol, which was noticed through inhibition of proinflammatory markers, and the decrease in capillary permeability.

Conclusion: Topical Aescin alone or in combination with clobetasol reduced Ki-67 expression successfully; furthermore, the combination of topical Aescin and Clobetasol decreased TNF- score and had the strongest anti-inflammatory activity more than the other groups. Lastly Aescin was able to alter the histopathologic features of the psoriatic skin through its anti-inflammatory, venotonic and anti-edematous activity.

References

- Zhou X, Chen Y, Cui L, Shi Y, Guo C. Advances in the pathogenesis of psoriasis: From keratinocyte perspective. Cell death & disease. 2022 Jan 24;13(1):81. DOI: https://doi.org/10.1038/s41419-022-04523-3

- Prinz JC, Choon SE, Griffiths CE, Merola JF, Morita A, Ashcroft DM, Viguier M. Prevalence, comorbidities and mortality of generalized pustular psoriasis: A literature review. Journal of the European Academy of Dermatology and Venereology. 2023 Feb;37(2):256-73. DOI: https://doi.org/10.1111/jdv.18720

- Armstrong A, Bohannan B, Mburu S, Alarcon I, Kasparek T, Toumi J, Frade S, Barrio SF, Augustin M. Impact of psoriatic disease on quality of life: interim results of a global survey. Dermatology and Therapy. 2022 Apr;12(4):1055-64. DOI: https://doi.org/10.1007/s13555-022-00695-0

- De Alcantara CC, Reiche EM, Simão AN. Cytokines in psoriasis. Advances in Clinical Chemistry. 2021 Jan 1; 100:171-204. DOI: https://doi.org/10.1016/bs.acc.2020.04.004

- Rendon A, Schäkel K. Psoriasis pathogenesis and treatment. International journal of molecular sciences. 2019 Mar 23;20(6):1475. DOI: https://doi.org/10.3390/ijms20061475

- Tang X, Chen L. The risk of organ-based comorbidities in psoriasis: a systematic review and meta-analysis. Anais brasileiros de dermatologia. 2022 Sep 30; 97:612-23. DOI: https://doi.org/10.1016/j.abd.2021.10.007

- Marrakchi S, Puig L. Pathophysiology of generalized pustular psoriasis. American Journal of Clinical Dermatology. 2022 Jan;23(Suppl 1):13-9. DOI: https://doi.org/10.1007/s40257-021-00655-y

- Luengas‐Martinez A, Hardman‐Smart J, Paus R, Young HS. Vascular endothelial growth factor‐A as a promising therapeutic target for the management of psoriasis. Experimental dermatology. 2020 Aug;29(8):687-98. DOI: https://doi.org/10.1111/exd.14151

- Geisler R, Prévost S, Dattani R, Hellweg T. Effect of Cholesterol and Ibuprofen on DMPC- β-Aescin Bicelles: A Temperature-Dependent Wide-Angle X-ray Scattering Study. Crystals. 2020 May;10(5):401. DOI: https://doi.org/10.3390/cryst10050401

- Khushnuma R, Dakshina G, Anubhav D, Yatendra S. A REVIEW ON β-ESCIN. Indian Journal of Medical Research and Pharmaceutical Sciences. 2021;8(1):10-6. DOI: https://doi.org/10.29121/ijmrps.v8.i1.2020.2

- Gözcü S. Aesculus hippocastanum L. InNovel Drug Targets with Traditional Herbal Medicines 2022 (pp. 23-36). Springer, Cham. DOI: https://doi.org/10.1007/978-3-031-07753-1_2

- Gallelli L. Escin: A review of its anti-edematous, anti-inflammatory, and venotonic properties. Drug design, development and therapy. 2019; 13:3425. DOI: https://doi.org/10.2147/DDDT.S207720

- Yang Y, Wang L, Yuan M, Yu Q, Fu F. Anti-Inflammatory and gastroprotective effects of escin. Natural Product Communications. 2020 Dec 1;15(12):1934578X20982111. DOI: https://doi.org/10.1177/1934578X20982111

- Al-Mayahy MH, Marlow M, Scurr DJ. The Complementary Role of ToF-SIMS in the Assessment of Imiquimod Permeated into the Skin from a Microemulsion Dosage Form. Al Mustansiriyah Journal of Pharmaceutical Sciences. 2019 Dec 1;19(4):196-210. DOI: https://doi.org/10.32947/ajps.v19i4.650

- Gangwar RS, Gudjonsson JE, Ward NL. Mouse models of psoriasis: a comprehensive review. Journal of Investigative Dermatology. 2022 Mar 1;142(3):884-97. DOI: https://doi.org/10.1016/j.jid.2021.06.019

- Shinno-Hashimoto H, Eguchi A, Sakamoto A, Wan X, Hashimoto Y, Fujita Y, Mori C, Hatano M, Matsue H, Hashimoto K. Effects of splenectomy on skin inflammation and psoriasis-like phenotype of imiquimod-treated mice. Scientific Reports. 2022 Aug 30;12(1):14738. DOI: https://doi.org/10.1038/s41598-022-18900-7

- Rasmussen OF, Rudbeck L. Immunohistochemistry: An Agilent Perspective. InHandbook of Practical Immunohistochemistry: Frequently Asked Questions 2022 Jun 15 (pp. 47-57). Cham: Springer International Publishing. DOI: https://doi.org/10.1007/978-3-030-83328-2_4

- Hasic E. Immunohistochemistry Fundamentals. Immunohistochemistry: A Technical Guide to Current Practices. 2022 Jul 7:1. DOI: https://doi.org/10.1017/9781009106924.002

- Wu Y, Cheng M, Huang S, Pei Z, Zuo Y, Liu J, Yang K, Zhu Q, Zhang J, Hong H, Zhang D. Recent advances of deep learning for computational histopathology: Principles and applications. Cancers. 2022 Feb 25;14(5):1199. DOI: https://doi.org/10.3390/cancers14051199

- Naik DA, Mohana RM, Ramu G, Lalitha YS, SureshKumar M, Raghavender KV. Analyzing histopathological images by using machine learning techniques. Applied Nanoscience. 2023 Mar;13(3):2507-13. DOI: https://doi.org/10.1007/s13204-021-02217-4

- Al-Hashemi EH. Anti-Neutrophil Antibodies (ANCA) Level in Psoriatic Patients with Different Degree of Severity. Al Mustansiriyah Journal of Pharmaceutical Sciences. 2015 Dec 1;15(2):29-40. DOI: https://doi.org/10.32947/ajps.v15i2.168

- Boswell ND, Cook MK, Balogh EA, Feldman SR. The impact of complete clearance and almost complete clearance of psoriasis on quality of life: a literature review. Archives of Dermatological Research. 2023 May;315(4):699-706. DOI: https://doi.org/10.1007/s00403-022-02420-5

- Andrés-Sánchez N, Fisher D, Krasinska L. Physiological functions and roles in cancer of the proliferation marker Ki-67. Journal of Cell Science. 2022 Jun 1;135(11): jcs258932. DOI: https://doi.org/10.1242/jcs.258932

- Polewski MD, Nielsen GB, Gu Y, Weaver AT, Gegg G, Tabuena-Frolli S, Cajaiba M, Hanks D, Press MF, Gottstein C, Gruver AM. A standardized investigational Ki-67 immunohistochemistry assay used to assess high-risk early breast cancer patients in the monarchE phase 3 clinical study identifies a population with greater risk of disease recurrence when treated with endocrine therapy alone. Applied Immunohistochemistry & Molecular Morphology. 2022 Apr 22;30(4):237-45. DOI: https://doi.org/10.1097/PAI.0000000000001009

- Abdelsalam HF, Gobran MA, Abdelwahab MM, Abdelaziz HR. A Comparative Study of Psoriasis and Psoriasiform Dermatoses on Basis of Ki-67 Immunohistochemical Expression. The Egyptian Journal of Hospital Medicine. 2022 Jan 1;86(1):840-4. DOI: https://doi.org/10.21608/ejhm.2022.218029

- Jang DI, Lee AH, Shin HY, Song HR, Park JH, Kang TB, Lee SR, Yang SH. The role of tumor necrosis factor alpha (TNF-α) in autoimmune disease and current TNF-α inhibitors in therapeutics. International journal of molecular sciences. 2021 Mar 8;22(5):2719. DOI: https://doi.org/10.3390/ijms22052719

- Raafat M, Kamel AA, Shehata AH, Ahmed AS, Bayoumi AM, Moussa RA, Abourehab MA, El-Daly M. Aescin protects against experimental benign prostatic hyperplasia and preserves prostate histomorphology in rats via suppression of inflammatory cytokines and COX-2. Pharmaceuticals. 2022 Jan 22;15(2):130. DOI: https://doi.org/10.3390/ph15020130

- Gallelli L, Cione E, Wang T, Zhang L. Glucocorticoid-like activity of escin: A new mechanism for an old drug. Drug Design, Development and Therapy. 2021 Feb 24:699- 704. DOI: https://doi.org/10.2147/DDDT.S297501