Tissue factor inhibitory flavonoids from the fruits of Chaenomeles sinensis

Tissue factor (TF, tissue thromboplastin or coagulation factor 111) accelerates the blood clotting, activating both the intrinsic and the extrinsic pathways to serve as a cofactor. In order to isolate TF inhibitors from the fruits of Chaenomeles sinensis, an activity-guided purification utilizing a bio-assay method of prothrombin time prolongation, was carried out to yield five active flavoniods such as hovetrichoside C (1) (IC50 = 14.0 mug), luteolin-7-O-beta-D-glucuronide (3) (IC50 = 31.9 mug), hyperin (4) (IC50 = 20.8 mug), avicularin (6) (IC50 = 54.8 mug) and quercitrin (10) (IC50 = 135.7 mug), along with other inactive compounds such as (+/-)-(2E,4E)-O-beta-D-glucopyranosyl-4'-hydroxy-beta-ionylideneacetic acid ester (2), genistein-7-O-beta-D-glucopyranoside (5), luteolin-3'-methoxy-4'-O-beta-D-glucopyranoside (7), luteolin-7-O-beta-D-glucuronide methyl ester (8), tricetin-3'-methoxy-4'-O-beta-D-glucopyranoside (selagin-4'-O-beta-D-glucopyranoside) (9), (-)-epicatechin (11), luteolin-4'-O-beta-D-glucopyranoside (12) and apigenin-7-O-beta-D-glucuronide methyl ester (13). The structures of the isolated compounds were elucidated through spectral analysis. Among them, compounds 1 to 9, 12 and 13 were isolated for the first time from the fruits of this plant and the compound 9 is a new flavonoid.