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

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

Keywords:

• Psoriasis
• imiquimod
• ustekinumab
• curcumin
• antioxidant
• anti-inflammatory

Ethical approval

All animals were treated following the Guide for the Care and Use of Laboratory Animals as adopted by the US National Institutes of Health. Approval was granted by the Ethics Committee of Qassim University (Cams1-2018–1-14-S-3581).

Acknowledgments

The authors gratefully acknowledge Qassim University, represented by the Deanship of Scientific Research, for the financial support of this research under grant number Cams1-2018-1-14-S-3581 during the academic year 1439 AH/ 2018 AD.

Author contributions

Conceptualization, Ayman M. Mousa; funding acquisition, Ayman M. Mousa and Fahad A. Alhumaydhi; data curation, Ahmed Abdellatif, Osamah Al Rugaie, Abdullah Alnuqaydan Sayed Y Elsheikh, Abdullah S Aljohani, Ameen S. S. Alwashmi, and Mohammad Aljasir; formal analysis, Fahad A. Alhumaydhi, Ahmed Abdellatif, Suliman A. Alsagaby, Ali Yousif Babiker, Sultan A Alsuhaibani, Ahmed M S Hegazy and Osamah Al Rugaie; investigations, Ahmed Abdellatif, Abdullah Alnuqaydan, and Waleed Al Abdulmonem; methodology, Ayman M. Mousa, Sayed Y Elsheikh, Waleed Al Abdulmonem, Ahmed M S Hegazy, Ali Yousif Babiker, Sultan A Alsuhaibani, Mohammad S. Alkhowailed, Abdullah S Aljohani, Ameen S. S. Alwashmi, Mohammad Aljasir, Khaled E.A. Soliman, Mohamad Y R Yosof, and Hanan S Seleem; resources, Fahad A. Alhumaydhi, Osamah Al Rugaie, Abdullah Alnuqaydan, Suliman A. Alsagaby, Mohammad S. Alkhowailed, Abdullah S Aljohani, Ameen S. S. Alwashmi, Mohammad Aljasir, Khaled E.A. Soliman, Mohamad Y R Yosof, Ahmed M S Hegazy, and Hanan S Seleem; software, Ahmed Abdellatif, Khaled E.A. Soliman, Waleed Al Abdulmonem, Mohamad Y R Yosof, and Hanan S Seleem; validation, and Abdullah Alnuqaydan, Abdullah S Aljohani, Mohammad S. Alkhowailed, Ameen S. S. Alwashmi, Mohammad Aljasir, Khaled E.A. Soliman, Mohamad Y R Yosof, and Hanan S Seleem; visualisation, Khaled E.A. Soliman, Osamah Al Rugaie, Mohamad Y R Yosof, Ali Yousif Babiker, Sultan A Alsuhaibani, and Hanan S Seleem; writing – original draft, Ayman M. Mousa, Fahad A. Alhumaydhi, and Suliman A. Alsagaby; writing – review & editing, Ayman M. Mousa, Ahmed Abdellatif, and Abdullah Alnuqaydan; supervision, Ayman M. Mousa and Fahad A. Alhumaydhi; Project administration, Ayman M. Mousa;

Disclosure statement

The authors declare no conflicts of interest in this study. The funder had no role in the study’s design, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.

Data availability statement

The data presented in this study are available on request from the corresponding author.

Additional information

Funding

The present work was financially supported by the Deanship of Scientific Research, Qassim University under grant number [Cams1-2018–1-14-S-3581] during the academic year 2018 AD.