School of Pharmaceutical Sciences, Guizhou University, Guiyang, 550025, China.
Z Naturforsch C J Biosci. 2020 Jul 3;76(1-2):11-19. doi: 10.1515/znc-2019-0223. Print 2021 Jan 27.
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.
组织因子（TF）在止血和血栓形成中起着关键作用，似乎是一个有吸引力的靶点，具有抑制 TF 活性的生物碱的药用植物有益于心血管疾病（CVD）。本研究的目的是进一步探讨生物碱和 TF 的知识。通过简化显色测定法测定 TF 促凝活性，然后通过逆转录和聚合酶链反应检查其 mRNA 表达。此外，通过分子对接分析了四种代表性生物碱与 TF/FVIIa 的结合潜力。结果表明，这些具有不同结构的异喹啉生物碱对抑制 TF 活性有不同的影响。分子对接显示，包括 l-藜芦定、小檗碱、黄连碱和延胡索乙素在内的四种生物碱稳定地位于 TF/FVIIa 的活性结合口袋中。SARs 分析表明，结构差异包括平面、季铵氮以及 C-8、C-9、C-10 上的外围官能团，对抑制 TF 活性有很强的影响，为修饰异喹啉生物碱以抑制 TF 活性提供了有效的方法。本研究为异喹啉生物碱的心血管保护提供了进一步的证据，在临床应用异喹啉生物碱或其潜在类似物治疗 CVD 的挑战方面具有生理意义。
