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Arbutin attenuates CFA-induced arthritis by modulating expression levels of 5-LOX, NF‑κB, IL-17, PGE-2 and TNF-α

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Abstract

Arbutin, a naturally soluble glycosylated phenol has antioxidant, antimicrobial, antitumor and anti-inflammatory properties. The current exploration appraises the treatment of arthritis by use of Arbutin (25, 50 and 100 mg/kg) orally in CFA-induced rat arthritis model. Body weight changes, paw size, and joint diameter were recorded till the 28th day in the arthritic-induced rats. Hematological, biochemical, oxidative and inflammatory biomarkers were measured through the blood samples of anesthetized rats. Arbutin markedly decreased paw volume, PGE-2, anti-CCP and 5-LOX levels, however, maintained metabolic and hematological balance and prevented weight loss. Radiology and histology changes improved significantly in the ankle joints of rats. Moreover, Arbutin increased gene pointers such as IL-10 and IL-4 while significantly reducing the levels of CRP and WBCs, whereas Hb, platelets and RBCs count markedly raised in post-treatments. Antioxidant levels of SOD, CAT and GSH were improved and MDA level was reduced in treated groups. Rt-PCR investigation showed a significant reduction of the interleukin-1β, TNF-α, interleukin-6, cyclooxygenase-2, NF-κB and IL-17 and increased expression of gene pointers like IL-4, and IL-10 in treated groups. Assessment of molecular docking revealed a strong binding interaction of Arbutin against 5-LOX, IL-17, TNF-alpha and interleukin-6, cyclooxygenase-2, nuclear factor-κB, IL-4 and iNOS providing a strong association between experimental and theoretical results. As a result, Arbutin has significantly reduced CFA-induced arthritis by modulation of anti-inflammatory cytokines, i.e., IL-10 and IL-4, the pro-inflammatory cytokines panel such as NF-κB, TNF-alpha, IL-1β, IL-6, PGE-2, 5-LOX and COX-2 and oxidative biomarkers.

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Acknowledgements

The authors express their gratitude to the University of Sargodha, Sargodha, Pakistan’s College of Pharmacy (Post Graduate Pharmacology Lab.) for the technical facilities provided.

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Authors and Affiliations

  1. Department of Pharmacology, College of Pharmacy, University of Sargodha, Sargodha, 40100, Pakistan

    Nabeela Tabassum Sial, Abdul Malik & Urooj Iqbal

  2. Department of Pharmacology, Institute of Pharmacy, Faculty of Pharmaceutical and Allied Health Sciences, Lahore College for Women University, Jail Road, Lahore, 54000, Pakistan

    Nabeela Tabassum Sial

  3. Institute of Chemistry, University of Sargodha, Sargodha, 40100, Pakistan

    Muhammad Fayyaz ur Rehman

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  1. Nabeela Tabassum Sial
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  2. Abdul Malik
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Contributions

The study was supervised and designed by AM. Data collection, material preparation and experiments were performed by NTS. UI facilitated for performing rt-PCR, ELISA and compilation of results, while in silico studies were interpreted by FM. Data analysis was done by NTS and AM. Manuscript drafted by NTS and AM. The final manuscript was read and approved by all the authors.

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Correspondence to Abdul Malik.

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Sial, N.T., Malik, A., Iqbal, U. et al. Arbutin attenuates CFA-induced arthritis by modulating expression levels of 5-LOX, NF‑κB, IL-17, PGE-2 and TNF-α. Inflammopharmacol (2024). https://doi.org/10.1007/s10787-024-01480-5

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