Effects of lobetyolin on xanthine oxidase activity in vitro and in vivo: weak and mixed inhibition.

Lobetyolin (LBT), a general marker compound mainly found in Codonopsis plants including C. pilosula, C. tubulosa, and C. lanceolata, exhibits antitumor, antiviral, anti-inflammatory, mucosal protective, and antioxidant activities. Xanthine oxidase (XO) catalyzes the formation of uric acid from xanthine, a critical metabolic pathway related to hyperuricemia and gout. The aim of this study was to investigate the effect of LBT on XO activity and its mechanism using in vitro enzyme assay system and in vivo potassium oxonate-induced hyperuricemic mice. LBT was found to weakly inhibit XO activity via a mixed type mechanism. Consistently, the impact of 1-week oral LBT treatment on serum XO activity in vivo is limited in hyperuricemic mice. However, oral LBT at 50 mg/kg significantly reduced hepatic XO activity in vivo. To the best of our knowledge, this is the first study to report effects of LBT on XO activity and its inhibition mechanism.