Anti-hyperuricemic and Anti-gout Effects of Olive Juice Freeze Dried Powder in Rats

Abstract

To investigate the anti-hyperuricemic and anti-gout effects of olive juice freeze dried powder(Hidrox®12%) and its underlying mechanisms, a hyperuricemia rat model was established by intraperitoneal injection of potassium oxazinate and was given olive juice freeze dried powder administration. The levels of serum uric acid(UA), creatinine(CR) and urea nitrogen(BUN), serum and hepatic xanthine oxidase(XOD) activities, and the protein expression level of urate transporter 1(URAT1) in kidney were evaluated. Besides, a gout rat model induced by monosodium urate(MSU) was established to detect the effects of olive juice freeze dried powder on the paw swelling rate, and the level of TNF-α and IL-1β in serum. UPLC-ESI-MS/MS method was used to separate and identify the active ingredients for lowering UA. Results showed that, when compared with the model group, olive juice freeze dried powder（80 mg/kg） could significantly reduce the serum UA level(P<0.01) and reverse the elevated serum CR and BUN(P<0.01) levels caused by hyperuricemia. Further study revealed that the anti-hyperuricemic effect of olive juice freeze dried powder might be associated with its inhibition toward the serum and hepatic XOD activities and the downregulation of renal URAT1 expression. In the gouty model, olive juice freeze dried powder(80 mg/kg) significantly alleviated the joint swelling(P<0.001) caused by MSU and reduced the serum TNF-α and IL-1β levels respectively(P<0.05). Further study revealed that piperine and luteolin might be the active ingredients of olive juice freeze dried powder owing to their inhibitory activity on URAT1-mediated urate transport in vitro. In summary, olive juice freeze dried powder could alleviate hyperuricemia and acute gouty arthritis in vivo, the uric acid-lowering effect of which might be related to the inhibition of XOD activities and down-regulation of renal URAT1 expression as well as inhibiting inflammatory reactions.