Anti-complementary anthraquinones from Polygonum cuspidatum and their action targets / 中草药

ABSTRACT

Objective: To study the anti-complementary anthraquinones from Polygonum cuspidatum and their action targets. Methods: The anti-complementary activity-directed isolation was carried out with the hemolysis test as guide. All isolates were evaluated for their in vitro anti-complementary activities. The action targets of the main bioactive constituents were also examined using complement-depleted sera. Results: Ten anthraquinones and three other compounds were isolated from the EtOAc fraction of P. cuspidatum extract, including physcion (1), chrysophanol (2), questin (3), emodin-8-O-β-D-glucoside (4), emodin (5), rhein (6), fallacinol (7), citreorosein (8), xanthorin (9), isorhodoptilometrin (10), 2, 5-dimethyl-7-hydroxychromone (11), 7-hydroxy-4-methoxy-5-methylcoumarin (12), and 5, 7-dihydroxy-1-isobenzofuranone (13). Compounds 9 and 10 were isolated from the the plants of Polygonaceae for the first time, and compound 9 was the alizarin-type anthraquinone first obtained from P. cuspidatum. Compounds 3-9 showed the anti-complementary activity in different degrees, and compound 7 exhibited the most significant activity against the classical and alternative pathway [CH50 = (6 ± 2) μg/mL, AP50 = (50 ± 5) μg/mL]. The study on the preliminary mechanism revealed that compound 4 interacted with C1q, C2, and C9 in complement activation cascade, while compound 7 acted on C1q, C2, C4, and C9. Conclusion: The anthraquinones are main anti-complementary constituents in P. cuspidatum; and fallacinol (7) is a potential complement inhibitor with strong activity and definite targets, which should be further studied in future.