Anti-hyperuricemia natural products from medicinal plants used by local tribes in Indonesia

Hyperuricemia, results from the overproduction or underexcretion of uric acid. During the last step of purine metabolism, xanthine oxidase (XO) catalyzes the oxidation of xanthine and hypoxanthine into uric acid [1]. XO inhibitor has the potential to be a therapeutic agent for hyperuricemia and ROS-induced diseases [2]. Allopurinol, an XO inhibitor that has been used clinically for several decades possesses some unwanted negative effects such as hepatitis, allergies and toxicity of 6-mercaptopurine [3]. In our search into natural antihyperuricemia agents, extracts of 30 medicinal plants from 19 families were evaluated by the XO inhibitory assay. Of the 30 extracts assayed, extracts from Sonneratia caseolaris (Sonneratiaceae) leaves and Zingiber purpureum (Zingiberaceae) rhizome displayed potential to inhibit the XO with activity greater than 50% at 50 mg/mL. Bioassay-guided fractionation of the leaves extract of S. caseolaris , led to the isolation of compound 1, identified as luteolin-7-O-glucoside. Simultaneously, XO inhibitory assay-guided isolation of the extract of Z. purpurea rhizome gave compound 2, identified as 3-(3,4-dimethoxyphenyl)-3,4-dimethoxystyryl-cyclohex-1-ene. Compounds 1 and 2 inhibited the activity of XO with the IC 50 values of 12 mg/mL and 27 mg/mL, respectively. Allopurinol showed IC 50 value of 6 mg/mL in our XO inhibitory activity assay. Fig. 1: Sonneratia caseolaris leaves (upper left) and Zingiber purpurea rhizome (lower left) and the isolated xanthine oxidase inhibitory compounds. References: [1] Nguyen MTT, Awale S, Tezuka Y, Tran QL, Watanabe H, Kadota S. Xanthine oxidase inhibitory activity of Vietnamese medicinal plants. Biol Pharm Bull 2004; 27:1414 – 1421 [2] Lin H-C, Tsai S-H, Chen C-S, Chang YC, Lee CM, Lai ZY, Lin CM. Structure-activity relationship of coumarin derivatives on xanthine oxidase-inhibiting and free radical-scavenging activities. Biochem Pharmacol 2008; 75: 1416 – 1425 [3] Stockert AL, Stechschulte M. Allopurinol to febuxostat: How far have we come. Clinical Medicine Insights: Therapeutics 2010; 2: 927 – 945.