目的 研究虎杖Polygonum cuspidatum中的抗补体活性蒽醌类成分及其作用靶点。方法 采用溶血试验法进行抗补体活性成分的导向分离，对所得化合物进行抗补体活性测定，并利用补体缺失血清鉴定主要活性化合物的作用靶点。结果 从虎杖醋酸乙酯活性部位分离得到10个蒽醌类和3个其他类成分，分别鉴定为大黄素甲醚（1）、大黄酚（2）、大黄素-8-甲醚（3）、大黄素-8-O-β-D-葡萄糖苷（4）、大黄素（5）、大黄酸（6）、迷人醇（7）、6-羟基芦荟大黄素（8）、xanthorin（9）、isorhodoptilometrin（10）、2, 5-二甲基-7-羟基-色原酮（11）、7-羟基-4-甲氧基-5-甲基-香豆素（12）和5, 7-二羟基-异苯并呋喃酮（13）。化合物9、10为首次从蓼科中分离得到，化合物9是首次从虎杖中发现的茜草素型蒽醌；化合物3～9对补体系统的经典和旁路途径有不同程度的抑制活性，以化合物7的活性最显著 [CH₅₀＝（6±2）μg/mL；AP₅₀＝（50±5）μg/mL]。靶点研究表明，化合物4作用于补体系统的C1q、C2及C9组分；化合物7作用于C1q、C2、C4及C9组分。结论 蒽醌类化合物是虎杖的主要抗补体活性成分，迷人醇活性强、靶点明确，值得深入研究。

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.

国家自然科学基金资助项目（30925042）；科技部重大专项资助项目(2009ZX09502-013)；《中国药典》国家药品标准提高研究项目（369，虎杖）