Immunosuppression by piperine as a regulator of the NLRP3 inflammasome through MAPK/NF-κB in monosodium urate-induced rat gouty arthritis

Vet World Vol.15 February-2022 Article-8

Research Article

Veterinary World, 15(2): 288-298

https://doi.org/10.14202/vetworld.2022.288-298

Galih Aji Kuncoro Jati¹, Nazzun Assihhah¹, Anas Ardiana Wati², and Siti Isrina Oktavia Salasia¹

1. Department of Clinical Pathology, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia.
2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia.

Background and Aim: Gouty arthritis is a metabolic disorder involving monosodium urate (MSU) crystal deposition as a key initiator of acute inflammation. Dysregulation of the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome is associated with the pathogenesis of gout through the maturation of interleukin-1β. Piperine (PIP) is a phytochemical with an anti-inflammatory activity that has the potential as an alternative treatment for gout. In this study, we examined the effect of PIP in immunosuppression of gout inflammation through the regulation of the NLRP3 inflammasome.

Materials and Methods: An in silico study was done by pharmacodynamic modeling of PIP in suppressing MSU-induced inflammation through disruption of the NLRP3 inflammasome. In vivo tests, including inflammatory assessment, histopathology, cytology, estimation of lipid peroxidation index, and detection of systemic inflammatory reactants, were performed on two groups using preventive and curative protocols.

Results: In silico studies of molecular docking demonstrated the activity of PIP as a competitive inhibitor of the mitogen-activated protein kinases/nuclear factor-kappaB axis, upstream of the NLRP3 inflammasome. Analysis of gout models with curative and preventive protocols revealed the immunosuppression activity of PIP by reducing inflammatory symptoms, inhibiting tophus formation resulting from NETosis, reducing cartilage erosion, inhibiting leukocyte exudation, suppressing lipid peroxidation index, and inhibiting the production of C-reactive protein.

Conclusion: The results demonstrate the activity of PIP as an immunosuppressant in gout flare. These findings indicate the potential of PIP as a candidate for prophylactic and therapeutic agent for the treatment of gouty arthritis. Keywords: gout, immunosuppression, monosodium urate, NLRP3 inflammasome, piperine.

Keywords: gout, immunosuppression, monosodium urate, NLRP3 inflammasome, piperine.

How to cite this article: Jati GAK, Assihhah N, Wati AA, Salasia SIO (2022) Immunosuppression by piperine as a regulator of the NLRP3 inflammasome through MAPK/NF-κB in monosodium urate-induced rat gouty arthritis, Veterinary World, 15(2): 288-298.

Received: 24-10-2021 Accepted: 05-01-2022 Published online: 11-02-2022

Corresponding author: Siti Isrina Oktavia Salasia E-mail: isrinasalasia@ugm.ac.id

DOI: 10.14202/vetworld.2022.288-298

Copyright: Jati GAK, et al. This article is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.