Discovery of a novel rice-derived peptide with significant anti-gout potency.

As a metabolic disease, gout, which seriously affects the normal life of patients, has become increasingly common in modern society. However, the existing medicines cannot completely meet the clinical needs. In the current study, a novel short peptide (named rice-derived-peptide-2 (RDP2), AAAAGAMPK-NH2, 785.97 Da) was isolated and identified from water extract of shelled Oryza sativa fruits, without toxic side effects but excellent stability. Our results indicated that RDP2 (the minimum effective concentration is 5 µg kg-1) induced a significant reduction in serum uric acid levels in hyperuricemic mice via suppressing xanthine oxidase activity and urate transporter 1 expression, as well as alleviated renal damage through inhibiting the activation of NLRP3 inflammasome. In addition, RDP2 can also alleviate paw swelling and inflammatory reactions in mice after subcutaneous injection of monosodium urate crystals. As mentioned above, we obtained a novel peptide which could work through all stages of gout, not only reducing uric acid levels and renal damage in hyperuricemic mice, but also alleviating inflammatory responses associated with acute gout attack, and thus provided a new peptide molecular template for the development of anti-gout drugs.

RDP3, A Novel Antigout Peptide Derived from Water Extract of Rice.

Gout and hyperuricemia can seriously affect the quality of life; at present, however, existing medicines are unable to meet all clinical needs. In the current study, a novel peptide (i.e., rice-derived-peptide-3 (RDP3), AAAAMAGPK-NH2, 785.97 Da) in water extract obtained from shelled Oryza sativa fruits was identified. Testing revealed that RDP3 (minimum effective concentration 100 µg/kg) did not show both hemolytic and acute toxicity, and reduced uric acid levels in the serum of hyperuricemic mice by inhibiting xanthine oxidase activity and decreasing urate transporter 1 expression. RDP3 also alleviated renal injury in hyperuricemic mice by decreasing NLRP3 inflammasome expression. Furthermore, RDP3 alleviated formalin-induced paw pain and reduced monosodium urate crystal-induced paw swelling and inflammatory factors in mice. Thus, this newly identified peptide reduced uric acid levels and renal damage in hyperuricemic mice and showed anti-inflammatory and analgesic activities, indicating the potential of RDP3 as an antigout medicine candidate.

New Rice-Derived Short Peptide Potently Alleviated Hyperuricemia Induced by Potassium Oxonate in Rats.

Gout that caused by hyperuricemia affects human health seriously and more efficient drugs are urgently required clinically. In this study, a novel peptide named RDP1 (AAAAGAKAR, 785.91 Da) was identified from the extract of shelled fruits of Oryza sativa. Our results demonstrated that RDP1 (the minimum effective concentration is 10 µg/kg) could significantly reduce the serum uric acid and creatinine and alleviate hyperuricemic nephropathy in rats by intragastric administration. RDP1 inhibited xanthine oxidase, which also was verified at the animal level. Results from molecular docking indicated that RDP1 can inhibit uric acid formation by occupying the binding site of xanthine oxidase to xanthine. Besides, RDP1 showed no toxicity on rats and was stable in several temperatures, demonstrating its advantages for transportation. This research was the first discovery of antihyperuricemic peptide from the shelled fruits of O. Sativa and provided a new candidate for the development of hypouricemic drugs.