Curcumin and ustekinumab cotherapy alleviates induced psoriasis in rats through their antioxidant, anti-inflammatory, and antiproliferative effects,Cutaneous and Ocular Toxicology

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Curcumin and ustekinumab cotherapy alleviates induced psoriasis in rats through their antioxidant, anti-inflammatory, and antiproliferative effects
Cutaneous and Ocular Toxicology ( IF 1.6 ) Pub Date : 2021-11-25 , DOI: 10.1080/15569527.2021.2003377
Ayman M Mousa _{1,

2} , Fahad A Alhumaydhi ₃ , Ahmed A H Abdellatif _{4,

5} , Waleed Al Abdulmonem ₆ , Mohammad S AlKhowailed ₇ , Suliman A Alsagaby ₈ , Osamah Al Rugaie ₉ , Abdullah M Alnuqaydan ₁₀ , Abdullah S M Aljohani ₁₁ , Mohammad Aljasir ₃ , Ameen S S Alwashmi ₃ , Khaled E A Soliman _{9,

12} , Mohamad Y R Yosof _{9,

13} , Sayed Y Elsheikh ₃ , Ali Yousif Babiker ₃ , Sultan A Alsuhaibani ₃ , Ahmed M S Hegazy _{14,

15} , Hanan S Seleem _{9,

16}

Affiliation

Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia.
Faculty of Medicine, Department of Histology and Cell Biology, Benha University, Benha, Egypt.
Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia.
Department of Pharmaceutics, College of Pharmacy, Qassim University, Buraydah, Saudi Arabia.
Faculty of Pharmacy, Department of Pharmaceutics and Industrial Pharmacy, Al-Azhar University, Assiut, Egypt.
Department of Pathology, College of Medicine, Qassim University, Buraydah, Saudi Arabia.
Department of Dermatology, College of Medicine, Qassim University, Buraydah, Saudi Arabia.
Department of Medical Laboratories Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah, Saudi Arabia.
Department of Basic Medical Sciences, College of Medicine and Medical Sciences, Qassim University, Unaizah, Saudi Arabia.
Department of Medical Biotechnology, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia.
Department of Veterinary Medicine, College of Agricultural and Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia.
Department of Forensic Medicine and Clinical Toxicology, Sohag Faculty of Medicine, Sohag University, Sohag, Egypt.
Department of Medical Physiology, College of Medicine, Zagazig University, Al-Sharquia, Egypt.
Department of Anatomy and Embryology, faculty of medicine, Northern border university, Arar, Saudi Arabia.
Benha Faculty of Medicine, Department of Anatomy and Embryology, Benha university, Benha, Egypt.
Faculty of Medicine, Department of Histology and Cell Biology, Menoufia University, Shebin Elkoum, Egypt.

Abstract

Introduction

Psoriasis is a chronic multifactorial inflammatory disease that affects 3% of people worldwide. Ustekinumab is a selective anti-IL-12/23 biologic that alleviates psoriasis, and curcumin is a natural, effective dietary turmeric extract applied to treat numerous diseases through its antioxidant and anti-inflammatory effects.

Objective

The current study evaluated the therapeutic effects of curcumin and ustekinumab cotherapy (CUC) on imiquimod (IQ)-induced psoriasis in a rat model.

Materials and methods

Twenty rats were divided into four groups, G1 (control group), G2 (IQ-treated group), G3 (IQ + ustekinumab), and G4 (IQ + CUC). Clinical, histopathological (HP), immunohistochemical (IHC), antioxidant, and biochemical investigations evaluated the efficacy of these drugs for treating IQ induced-psoriasis.

Results

Rats of G2 exhibited clinical signs of psoriatic skin lesions (erythema, scaling, and skin thickening) with epidermal changes (acanthosis and parakeratosis). Additionally, the biochemical analysis revealed significant (p < 0.05) reductions in the levels of antioxidant biomarkers (SOD, GPx, and CAT) with significant (p < 0.05) elevations in psoriasis-related cytokines (TNF-α, IL-17A, IL-12P40, and IL-23). In contrast, CUC alleviated the psoriatic changes in G4 better than ustekinumab monotherapy in G3.

Conclusions

Ustekinumab inhibits the inflammatory cytokines IL-12P40 and IL-23, while curcumin has antioxidant effects (increasing SOD, GPx, and CAT levels) with anti-inflammatory effects (decreasing the proinflammatory cytokine TNF-α and IL-17). Therefore, CUC could be an excellent cost-effective regimen that can improve the treatment of psoriasis by the synergistic effects of CUC.

Highlights
IQ-induces psoriasis by elevating TNF-α, IL-17A, IL-12, and IL-23 and decreasing GPx, SOD, and CAT
Ustekinumab exhibits anti-inflammatory effects by inhibiting IL-12 and IL-23
Curcumin inhibits TNF-α and IL-17A, and increases GPx, SOD, and CAT levels
CUC mitigates psoriasis by synergistic antioxidant and anti-inflammatory effects
CUC inhibits TNF-α, IL-17A, IL-12, and IL-23 and increases GPx, SOD, and CAT levels

中文翻译：

姜黄素和优特克单抗联合疗法通过其抗氧化、抗炎和抗增殖作用减轻大鼠诱导的银屑病

摘要

介绍

银屑病是一种慢性多因素炎症性疾病，影响全球 3% 的人。Ustekinumab 是一种选择性抗 IL-12/23 生物制剂，可缓解银屑病，姜黄素是一种天然、有效的膳食姜黄提取物，通过其抗氧化和抗炎作用用于治疗多种疾病。

客观的

目前的研究在大鼠模型中评估了姜黄素和优特克单抗联合疗法 (CUC) 对咪喹莫特 (IQ) 诱导的银屑病的治疗效果。

材料和方法

20 只大鼠分为四组，G1（对照组）、G2（IQ 治疗组）、G3（IQ + ustekinumab）和 G4（IQ + CUC）。临床、组织病理学 (HP)、免疫组织化学 (IHC)、抗氧化剂和生化研究评估了这些药物治疗 IQ 诱导的银屑病的功效。

结果

G2 大鼠表现出银屑病皮肤病变的临床症状（红斑、脱屑和皮肤增厚），并伴有表皮变化（棘层肥厚和角化不全）。此外，生化分析显示抗氧化生物标志物（SOD、GPx 和 CAT）水平显着降低（p < 0.05），银屑病相关细胞因子（TNF-α、IL-17A、IL）显着升高（ p < 0.05） -12P40 和 IL-23)。相比之下，CUC 比 G3 中的优特克单抗单药治疗更能缓解 G4 中的银屑病变化。