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Review
. 2025 May;33(5):2307-2323.
doi: 10.1007/s10787-025-01741-x. Epub 2025 Apr 18.

Deciphering the role of cell signaling pathways in gout pathogenesis and the therapeutic potential of phytoconstituents in their modulation

Hrithik Dey  1 , Syed Salman Ali  2 , Vandana Arora Sethi  1
Affiliations
Review

Deciphering the role of cell signaling pathways in gout pathogenesis and the therapeutic potential of phytoconstituents in their modulation

Hrithik Dey et al. Inflammopharmacology. 2025 May.

Abstract

Purpose: Gout, a type of inflammatory arthritis, arises from the accumulation of monosodium urate crystals in joints, leading to severe pain and inflammation. While conventional treatments, such as uric acid-lowering agents and anti-inflammatory drugs, are effective, they are often associated with adverse effects. This review aims to explore the potential of phytoconstituents as alternative therapeutic agents for gout, focusing on their mechanisms of action and strategies to enhance their clinical efficacy.

Methods: A comprehensive literature review was conducted to analyze the role of phytochemicals in gout management. Key compounds such as quercetin, curcumin, and resveratrol were examined for their effects on inflammatory pathways, oxidative stress, and uric acid regulation. Furthermore, advancements in drug delivery systems, including nanotechnology-based formulations and CRISPR-mediated pathway modulation, were explored to address the limitations of phytoconstituents.

Results: Phytoconstituents demonstrated significant anti-inflammatory, antioxidant, and xanthine oxidase inhibitory properties. These compounds modulated critical pathways such as NF-κB, NLRP3 inflammasome, and MAPK, reducing inflammation, oxidative stress, and uric acid levels. However, poor bioavailability and rapid metabolism remain key challenges, necessitating advanced formulation strategies to enhance their therapeutic potential.

Conclusion: Phytoconstituents offer a promising alternative for gout treatment by targeting multiple pathogenic mechanisms. Integrating nanotechnology and gene-editing approaches may improve their bioavailability and therapeutic efficacy. Further research is warranted to facilitate clinical translation and optimize their application in gout management.

Keywords: Anti-inflammatory pathways; Cell signaling pathways; Gout; Inflammasome; Nanotechnology; Phytoconstituents; Xanthine oxidase inhibition.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare that they have no competing interests.

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