The anti-hyperuricemic effect of four astilbin stereoisomers in Smilax glabra on hyperuricemic mice

Ethnopharmacological relevance: Smilax glabra Roxb. (SG), a Chinese medicinal herb which called tufuling, is believed to be effective in treating hyperuricemia and gout symptoms. But the active substance and pharmacological mechanism of reducing uric acid remain unknown. This study aimed to obtain the total flavonoids including four astilbin stereoisomers and to examine their effects on reducing uric acid content in hyperuricemic mice. Materials and methods: The total flavonoids of S. glabra (TFSG) were purified and then analysed by HPLC-PDAMS. The effect of TFSG on the content of serum uric acid (SuA), Serum creatinine (Scr), blood urea nitrogen (BUN) and the activities of xanthine oxidase (XOD) in hyperuricemic mouse model induced by potassium oxonate were examined. Western blot and PCR method were also used to investigate whether TFSG have effect on renal transport protein organic anion transporter 1 (OAT1), organic cation/carnitine transporter 2 (OCTN2) and their mRNA in hypeuricemic mice. Result: Total flavonoids were obtained from EtOAc soluble portion of S. glabra. Four compounds were identified as neoastilbin, astilbin, neoisoastilbin and isoastilbin, which accounted for 55.6% of total flavonoids. TFSG could significantly reduce the serum uric acid content in hyperuricemic mouse (p < 0.01 or p < 0.05). The activities of hepatic XOD have been reduced in hyperuricemic mouse administered with 125 mg/kg TFSG (p < 0.05). The expressions of renal OAT1, OCTN2 and their mRNA have been up-regulated in hyperuricemic mice administered with TFSG (250, 125 mg/kg) (p < 0.01or p < 0.05). TFSG (62.5 mg/kg) could also elevated the expression of renal OCTN2 (p < 0.05). Conclusion: A novel and simple method for preparative separation of astilbin stereoisomers from S. glabra was developed. It was the first time to obtain total flavonoids (including four marker compounds) of S. glabra, and the total content was up to 55.6%. The results suggested TFSG has significant effect on reducing uric acid in hyperuricemic mice by inhibiting the XOD activities and up-regulating the expression of OAT1, OCTN2 and their mRNA in kidney tissue.