University of Regensburg, Pharmaceutical Biology, Universitätsstr. 31, 93053 Regensburg, Germany.
Phytochemistry. 2013 Jun;90:106-13. doi: 10.1016/j.phytochem.2013.02.004. Epub 2013 Mar 13.
Rusci rhizoma extracts are traditionally used against chronic venous disorders (CVD). To determine the effect of its secondary plant metabolites on the endothelium, phenolic compounds and saponins from Butcher's broom were isolated from a methanolic extract, and their activity on the thrombin-induced hyperpermeability of human microvascular endothelial cells (HMEC-1) was investigated in vitro. In addition to the six known spirostanol saponins deglucoruscin (5), 22-O-methyl-deglucoruscoside (6), deglucoruscoside (7), ruscin (8), ruscogenin-1-O-(α-l-rhamnopyranosyl-(1→2)-β-d-galactopyranoside (9) and 1-O-sulpho-ruscogenin (10), three new spirostanol derivatives were isolated and identified: 3'-O-acetyl-4'-O-sulphodeglucoruscin (1), 4'-O-(2-hydroxy-3-methylpentanoyl)-deglucoruscin (2) and 4'-O-acetyl-deglucoruscin (3). Furthermore, the coumarin esculin (4), which is also prominently present in other medicinal plants used in the treatment of CVD, was isolated for the first time from Rusci rhizoma. Five of the isolated steroid derivatives (2, 5, 8, 9 and 10) and esculin (4) were tested for their ability to reduce the thrombin-induced hyperpermeability of endothelial cells in vitro, and the results were compared to those of the aglycone neoruscogenin (11). The latter compound showed a slight but concentration-dependent reduction in hyperpermeability to 71.8% at 100μM. The highest activities were observed for the spirostanol saponins 5 and 8 and for esculin (4) at 10μM, and these compounds resulted in a reduction of the thrombin-induced hyperpermeability to 41.9%, 42.6% and 53.3%, respectively. For 2, 5 and 8, the highest concentration tested (100μM) resulted in a drastic increase of the thrombin effect. The effect of esculin observed at a concentration of 10μM was diminished at 100μM. These in vitro data provide insight into the pharmacological mechanism by which the genuine spirostanol saponins and esculin can contribute to the efficacy of Butcher's broom against chronic venous disorders.
鲁斯可皂苷元提取物传统上用于治疗慢性静脉疾病 (CVD)。为了确定其次生植物代谢产物对内皮的影响，从金雀异黄素的甲醇提取物中分离出了酚类化合物和皂苷，并在体外研究了它们对凝血酶诱导的人微血管内皮细胞 (HMEC-1) 通透性增加的作用。除了六种已知的螺旋甾烷皂苷去葡萄糖苷 (5)、22-O-甲基-去葡萄糖苷 (6)、去葡萄糖苷 (7)、鲁斯可皂苷 (8)、鲁斯考苷元-1-O-(α-l-鼠李吡喃糖基-(1→2)-β-d-半乳糖苷 (9) 和 1-O-磺酸鲁斯考苷元 (10) 外，还分离并鉴定了三种新的螺旋甾烷衍生物：3'-O-乙酰基-4'-O-磺酸去葡萄糖苷 (1)、4'-O-(2-羟基-3-甲基戊酰基)-去葡萄糖苷 (2) 和 4'-O-乙酰基-去葡萄糖苷 (3)。此外，香豆素埃斯库林 (4) 也首次从鲁斯可根茎中分离出来，这种物质也存在于其他用于治疗 CVD 的药用植物中。从鲁斯可根茎中分离得到的甾体衍生物 (2、5、8、9 和 10) 和埃斯库林 (4) 中的五种被测试其降低凝血酶诱导的内皮细胞通透性的能力，并将结果与苷元 neo 鲁斯考苷元 (11) 的结果进行比较。后者在 100μM 时对高通透性的抑制作用仅略有但呈浓度依赖性，为 71.8%。在 10μM 时，螺旋甾烷皂苷 5 和 8 以及埃斯库林 (4) 的活性最高，这三种化合物分别使凝血酶诱导的通透性降低 41.9%、42.6%和 53.3%。对于 2、5 和 8，测试的最高浓度 (100μM) 导致凝血酶作用急剧增加。在 100μM 时，观察到的埃斯库林的作用在 10μM 时减弱。这些体外数据提供了对真正的螺旋甾烷皂苷和埃斯库林可促进金雀异黄素治疗慢性静脉疾病功效的药理学机制的深入了解。
