Evaluation of the Antihyperuricemic Activity of Phytochemicals from Davallia formosana by Enzyme Assay and Hyperuricemic Mice Model

Abstract

Abnormal serum urate levels are recognized as a critical factor in the progression of several chronic diseases. To evaluate the antihyperuricemic effect of Davallia formosana, the inhibitory activities of 15 isolated phytochemicals, including five novel compounds of 6,8-dihydroxychromone-7-C- β -d-glucopyranoside (1), 6,8,3',4'-tetrahydroxyflavanone-7-C- β -d-glucopyranoside (2), 6,8,4'-trihydroxyflavanone-7-C- β -d-glucopyranoside (3), 8-(2-pyrrolidinone-5-yl)-catechin-3-O- β -d-allopyranoside (4), and epiphyllocoumarin-3-O- β -d-allopyranoside (5), were examined against xanthine oxidase (XOD) and in a potassium oxonate-(PTO-) induced acute hyperuricemic mice model. The results indicated that compounds 3 and 5 significantly inhibited XOD activity in vitro and reduced serum uric acid levels in vivo. This is the first report providing new insights into the antihyperuricemic activities of flavonoid glycosides which can possibly be developed into potential hypouricemic agents.

Figure 1

Chemical structures of new compounds 1–5 isolated from the rhizome of Davallia formosana.

Figure 2

HMBC correlations of compound 4.

Figure 3

The xanthine oxidase- (XOD-) inhibitory activity of phytochemicals from Davallia formosana. AP, allopurinol (positive control); 2, 6,8,3′,4′-tetrahydroxyflavanone-7-C-β-d-glucopyranoside; 3, 6,8,4′-trihydroxyflavanone-7-C-β-d-glucopyranosid; 5, epiphyllocoumarin-3-O-β-d-allopyranoside. Each value represents the mean ± SEM of three replicates. *P < 0.05, **P < 0.01, and ***P < 0.001, compared to the positive control.

Figure 4

The uric acid-lowering effects of compounds 2, 3, and 5 from Davallia formosana on mice with potassium oxonate- (PTO-) induced hyperuricemia. The results are presented as the mean ± SEM (n = 6). *P < 0.005, **P < 0.001, and ***P < 0.0001, compared to the PTO-treated group.

Figure 5

Predicted binding mode of compound 5 docked into the active site of xanthine oxidase. The top and down pictures of each panel display the 3D and 2D structural docking patterns, respectively. The nitrogen and oxygen atoms are shown in dark blue and red colors, respectively. The hydrogen bond formation and the electrostatic interaction between compound 5 (yellow) and the amino acid residues (gray) of XOD are shown in green and light blue dashed lines, respectively.