Abstract Tissue factor (TF) which plays a key role in hemostasis and thrombosis appears to be an attractive target and medicinal plants having alkaloids inhibition TF activity benefit to cardiovascular disease (CVD). The aim of study is to explore further knowledge about alkaloids and TF. TF procoagulant activities were determined by the simplified chromogenic assay and their mRNA expression were then examined by reverse transcription and polymerase chain reaction. Besides, the potential of TF/FVIIa binding with four representative alkaloids were analyzed by molecular docking. The results indicated that these isoquinoline alkaloids with various structures had a different effect on suppression of TF activity. Molecular docking showed four alkaloids including l-corydalmine, berberine, jatrorrhizine, and tetrahydropalmatine were stably posed in the active binding pocket of TF/FVIIa. The SARs analysis showed the structural difference including planar, quaternary nitrogen, and the peripheral functional groups at C-8, C-9, C-10, have strong effect on inhibition of TF activity, which provided effective methods to modify isoquinoline alkaloids for inhibiting TF activity. This study provides a further evidence for the cardiovascular protection of isoquinoline alkaloids, and has physiological significance in the clinical challenge to use isoquinoline alkaloids or their potential analogs in the treatment of CVD.

中文翻译：

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11 种异喹啉生物碱抑制组织因子活性：构效关系和分子对接

摘要 在止血和血栓形成中起关键作用的组织因子 (TF) 似乎是一个有吸引力的目标，具有抑制 TF 活性的生物碱的药用植物对心血管疾病 (CVD) 有益。研究的目的是探索有关生物碱和TF的进一步知识。TF 促凝血活性通过简化的显色试验确定，然后通过逆转录和聚合酶链反应检查它们的 mRNA 表达。此外，通过分子对接分析了 TF/FVIIa 与四种代表性生物碱结合的潜力。结果表明，这些不同结构的异喹啉生物碱对TF活性的抑制作用不同。分子对接显示四种生物碱包括l-紫堇碱、小檗碱、药根碱、和四氢巴马汀稳定地置于 TF/FVIIa 的活性结合口袋中。SARs分析表明结构差异包括平面氮、季氮和C-8、C-9、C-10的外周官能团对TF活性的抑制作用较强，为修饰异喹啉生物碱以抑制TF活性提供了有效的方法。 TF 活动。本研究为异喹啉生物碱对心血管的保护作用提供了进一步的证据，在应用异喹啉生物碱或其潜在类似物治疗心血管疾病的临床挑战中具有生理意义。为修饰异喹啉生物碱抑制TF活性提供了有效的方法。本研究为异喹啉生物碱对心血管的保护作用提供了进一步的证据，在应用异喹啉生物碱或其潜在类似物治疗心血管疾病的临床挑战中具有生理意义。为修饰异喹啉生物碱抑制TF活性提供了有效的方法。本研究为异喹啉生物碱对心血管的保护作用提供了进一步的证据，在应用异喹啉生物碱或其潜在类似物治疗心血管疾病的临床挑战中具有生理意义。