Short Hexapeptide Optimized from Rice-Derived Peptide 1 Shows Promising Anti-hyperuricemia Activities

Plant-derived peptides are a treasure trove for new-generation anti-hyperuricemia drugs. In the current study, we optimized a short hexapeptide rice-derived peptide 1 (RDP1)-M3 (AAAAGA) according to the anti-hyperuricemia RDP1 peptide identified from rice in our previous research. Results showed that RDP1-M3 exerted better hyperuricemia-alleviating and xanthine oxidase (XOD)-inhibiting potency in mice than RDP1. The biodistribution of RDP1-M3 was also analyzed. RDP1-M3 directly decreased XOD and uric acid levels in vivo and in vitro. In addition, RDP1-M3 reduced the expression of urate transporter 1 and glucose transporter 9, increased the level of organic anion transporter 1, reduced the expression of NOD-like receptor superfamily pyrin 3 inflammasomes, and reduced the levels of interleukin-1β and tumor necrosis factor-α of hyperuricemic mice. Thus, our results indicated that the optimized short hexapeptide RDP1-M3 may be a candidate drug for anti-hyperuricemia.