A wild rice-derived peptide R14 ameliorates monosodium urate crystals- induced IL-1β secretion through inhibition of NF-κB signaling and NLRP3 inflammasome activation

Gout is an inflammatory arthritis initiated by the deposition of monosodium urate crystals (MSU) around the joints and surrounding tissues. MSU crystals activate the nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome to the release of interleukin-1 beta (IL-1 beta). Gout can have a substantial impact on patient's quality of life, and currently available medicines are unable to meet all the clinical needs. This study explored anti-gout potentials of the Rice14 (R14) peptide, a peptide derived from leaves of wild rice Oryza minuta. The effects of R14 peptide on IL-1 beta secretion in THP-1 macrophages with MSU crystals-induced inflammation were examined. Our results clearly showed that the R14 peptide significantly inhibited the secretion of IL-1 beta in MSU crystals-induced macrophages, and the effects were dose-related. For safety testing, the R14 peptide did not show both cytotoxicity and hemolytic activity. In addition, the R14 peptide strongly suppressed the phospho-I kappa B-alpha and nuclear factor kappa-B (NF-kappa B) p65 proteins in NF-kappa B signaling pathway, reduced the NLRP3 expression and inhibited the MSU crystals-mediated cleavage of caspase-1 as well as mature IL-1 beta. The R14 peptide also reduced MSU-triggered intracellular ROS levels in macrophages. Taken together, these results indicated that R14 peptide inhibited MSU crystals-induced IL-1 beta production through NF-kappa B and NLRP3 inflammasome activation. Our findings demonstrated that R14 peptide, the newly recognized peptide from wild rice, possessed potent regulatory activity against IL-1 beta production in MSU crystals-induced inflammation, and we therefore propose that the R14 peptide is a promising molecule with potential clinical application in the treatment of MSU crystals-induced inflammation.