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

Gout is a common and complex form of arthritis. It is related
 to purine metabolism disorders, which cause excessive uric acid
 production or poor uric acid excretion, with subsequent
 induction of hyperuricemia (HUA).1 Clinically, HUA is
 diagnosed when the level of serum uric acid is higher than
 420 μM in men and 360 μM in women.2 Continuous HUA can
 not only lead to an attack of gouty arthritis but can also cause
 kidney damage, cardiovascular events, and diabetes.1,3 In
 addition, if HUA is not properly treated and controlled, the
 recurrence, frequency, and degree of gout attack can also
 increase. Therefore, gout is best treated by controlling HUA.4
 The concentration of uric acid in the blood is primarily
 determined by the absorption and production of purine and by
 the decomposition and excretion of uric acid.5 Xanthine
oxidase (XOD), a key enzyme for the formation of uric acid, is
 a major target of inhibitory drugs5 such as allopurinol and
 febuxostat.4 During the process of uric acid metabolism in
 humans, about 65% of uric acid is filtered through the
 glomeruli, with 90% then reabsorbed into circulation through
 urate transporter-related proteins (such as URAT1) and the
 rest filtered into urine for excretion.5 Antihyperuricemic
 medicines, such as probenecid and benzbromarone, can
 significantly enhance the excretion of uric acid by inhibiting
URAT1.6 Currently, the treatment of the acute gout attack
 depends on drugs such as nonsteroidal anti-inflammatory
 drugs (NSAIDs), colchicine, glucocorticoids, and IL-1β
 antagonists.4 However, their clinical use has several limitations.
 For example, NSAIDs can induce peptic ulcers; allopurinol can
 produce severe skin rash and allergic reactions; febuxostat can
 lead to cardiovascular events; benzbromarone can induce
 hepatotoxic activity; and probenecid can generate uric acid
 crystals in the kidney.7−10 Therefore, the development of new
 antigout drugs remains an important focus.