DKB114, a mixture of chrysanthemum indicum linne flower and cinnamomum cassia (L.) J. Presl Bark extracts, improves hyperuricemia through inhibition of xanthine oxidase activity and increasing urine excretion

Abstract

Chrysanthemum indicum Linne flower (CF) and Cinnamomum cassia (L.) J. Presl bark (CB) extracts have been used as the main ingredients in several prescriptions to treat the hyperuricemia and gout in traditional medicine. In the present study, we investigated the antihyperuricemic effects of DKB114, a CF, and CB mixture, and the underlying mechanisms in vitro and in vivo. DKB114 markedly reduced serum uric acid levels in normal rats and rats with PO-induced hyperuricemia, while increasing renal uric acid excretion. Furthermore, it inhibited the activity of xanthine oxidase (XOD) in vitro and in the liver in addition to reducing hepatic uric acid production. DKB114 decreased cellular uric acid uptake in oocytes and HEK293 cells expressing human urate transporter (hURAT)1 and decreased the protein expression levels of urate transporters, URAT1, and glucose transporter, GLUT9, associated with the reabsorption of uric acid in the kidney. DKB114 exerts antihyperuricemic effects and uricosuric effects, which are accompanied, partially, by a reduction in the production of uric acid and promotion of uric acid excretion via the inhibition of XOD activity and reabsorption of uric acid. Therefore, it may have potential as a treatment for hyperuricemia and gout.