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ABSTRACT: 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-kappa B 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.
SUBMITTER: Jati GAK
PROVIDER: S-EPMC8980401 | biostudies-literature | 2022 Feb
REPOSITORIES: biostudies-literature
Veterinary world 20220211 2
<h4>Background and aim</h4>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 ...[more]