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姜黄素联合乌司奴单抗治疗通过抗氧化、抗炎和抗增殖作用缓解大鼠诱导性银屑病。

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

机构信息

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.

出版信息

Cutan Ocul Toxicol. 2022 Mar;41(1):33-42. doi: 10.1080/15569527.2021.2003377. Epub 2021 Nov 25.

DOI:10.1080/15569527.2021.2003377
PMID:34749565
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 ( < 0.05) reductions in the levels of antioxidant biomarkers (SOD, GPx, and CAT) with significant ( < 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.HighlightsIQ-induces psoriasis by elevating TNF-α, IL-17A, IL-12, and IL-23 and decreasing GPx, SOD, and CATUstekinumab exhibits anti-inflammatory effects by inhibiting IL-12 and IL-23Curcumin inhibits TNF-α and IL-17A, and increases GPx, SOD, and CAT levelsCUC mitigates psoriasis by synergistic antioxidant and anti-inflammatory effectsCUC inhibits TNF-α, IL-17A, IL-12, and IL-23 and increases GPx, SOD, and CAT levels.

摘要

简介

银屑病是一种慢性多因素炎症性疾病,影响全球 3%的人口。乌司奴单抗是一种选择性抗 IL-12/23 的生物制剂,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应用于治疗多种疾病。

目的

本研究评估姜黄素和乌司奴单抗联合治疗(CUC)对咪喹莫特(IQ)诱导的大鼠银屑病模型的治疗效果。

材料和方法

将 20 只大鼠分为 4 组,G1(对照组)、G2(IQ 处理组)、G3(IQ+乌司奴单抗)和 G4(IQ+CUC)。临床、组织病理学(HP)、免疫组织化学(IHC)、抗氧化和生化研究评估了这些药物治疗 IQ 诱导的银屑病的疗效。

结果

G2 组大鼠表现出银屑病皮肤病变的临床症状(红斑、鳞屑和皮肤增厚)和表皮变化(棘皮病和角化不良)。此外,生化分析显示抗氧化生物标志物(SOD、GPx 和 CAT)水平显著降低(<0.05),与银屑病相关的细胞因子(TNF-α、IL-17A、IL-12P40 和 IL-23)水平显著升高(<0.05)。相比之下,CUC 在 G4 中的缓解作用优于 G3 中的乌司奴单抗单药治疗。

结论

乌司奴单抗抑制炎症细胞因子 IL-12P40 和 IL-23,而姜黄素具有抗氧化作用(增加 SOD、GPx 和 CAT 水平)和抗炎作用(降低促炎细胞因子 TNF-α和 IL-17)。因此,CUC 可能是一种极好的具有成本效益的治疗方案,可以通过 CUC 的协同作用改善银屑病的治疗。

要点

IQ 通过升高 TNF-α、IL-17A、IL-12 和 IL-23 并降低 GPx、SOD 和 CAT 水平诱导银屑病。

乌司奴单抗通过抑制 IL-12 和 IL-23 发挥抗炎作用。

姜黄素抑制 TNF-α和 IL-17A,增加 GPx、SOD 和 CAT 水平。

CUC 通过协同抗氧化和抗炎作用减轻银屑病。

CUC 抑制 TNF-α、IL-17A、IL-12 和 IL-23 并增加 GPx、SOD 和 CAT 水平。

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