Wang Wei, Zhao Yuqing, Rayburn Elizabeth R, Hill Donald L, Wang Hui, Zhang Ruiwen
Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, Cancer Pharmacology Laboratory, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Cancer Chemother Pharmacol. 2007 Apr;59(5):589-601. doi: 10.1007/s00280-006-0300-z. Epub 2006 Aug 22.
Panax ginseng and its extracts have long been used for medical purposes; there is increasing interest in developing ginseng products as cancer preventive or therapeutic agents. The present study was designed to determine biological structure-activity relationships (SAR) for saponins present in Panax ginseng fruits.
Eleven saponins were extracted from P. ginseng fruits and purified by use of D(101) resin and ordinary and reverse-phase silica gel column chromatography. Their chemical structures were elucidated on the basis of physicochemical constants and NMR spectra. Compounds were then evaluated for SAR with their in vitro cytotoxicity against several human cancer cell lines.
The 11 compounds were identified as 20(R)-dammarane-3beta,12beta,20,25-tetrol (25-OH-PPD, 1); 20(R)-dammarane-3beta,6alpha,12beta,20,25-pentol (25-OH-PPT, 2); 20(S)-protopanaxadiol (PPD, 3); daucosterine 4, 20(S)-ginsenoside-Rh(2) (Rh(2), 5); 20(S)-ginsenoside-Rg(3) (Rg(3,) 6); 20(S)-ginsenoside-Rg(2) (Rg(2), 7); 20(S)-ginsenoside-Rg(1) (Rg(1), 8); 20(S)-ginsenoside-Rd (Rd, 9); 20(S)-ginsenoside-Re (Re, 10); and 20(S)-ginsenoside-Rb(1) (Rb(1), 11). Among the eleven compounds, 1, 3 and 5 were the most effective inhibitors of cell growth and proliferation and inducers of apoptosis and cell cycle arrest. For 1, the IC(50) values for most cell lines were in the range of 10-60 microM, at least twofold lower than for any of the other compounds. Compounds 1 and 3 had significant, dose-dependent effects on apoptosis, proliferation, and cell cycle progression.
The results suggest that the type of dammarane, the number of sugar moieties, and differences in the substituent groups affect their anti-cancer activity. This information may be useful for evaluating the structure/function relationship of other ginsenosides and their aglycones and for development of novel anticancer agents.
人参及其提取物长期以来一直用于医学目的；人们对开发人参产品作为癌症预防或治疗剂的兴趣与日俱增。本研究旨在确定人参果实中皂苷的生物构效关系（SAR）。
从人参果实中提取11种皂苷，并通过D(101)树脂以及普通和反相硅胶柱色谱法进行纯化。根据物理化学常数和核磁共振光谱阐明其化学结构。然后评估这些化合物对几种人类癌细胞系的体外细胞毒性的构效关系。
这11种化合物被鉴定为20(R)-达玛烷-3β,12β,20,25-四醇（25-OH-PPD，1）；20(R)-达玛烷-3β,6α,12β,20,25-五醇（25-OH-PPT，2）；20(S)-原人参二醇（PPD，3）；胡萝卜苷4，20(S)-人参皂苷-Rh(2)（Rh(2)，5）；20(S)-人参皂苷-Rg(3)（Rg(3)，6）；20(S)-人参皂苷-Rg(2)（Rg(2)，7）；20(S)-人参皂苷-Rg(1)（Rg(1)，8）；20(S)-人参皂苷-Rd（Rd，9）；20(S)-人参皂苷-Re（Re，10）；以及20(S)-人参皂苷-Rb(1)（Rb(1)，11）。在这11种化合物中，1、3和5是细胞生长和增殖的最有效抑制剂，也是细胞凋亡和细胞周期停滞的诱导剂。对于化合物1，大多数细胞系的IC(50)值在10 - 60微摩尔范围内，至少比其他任何化合物低两倍。化合物1和3对细胞凋亡、增殖和细胞周期进程具有显著的剂量依赖性作用。
结果表明达玛烷类型、糖基数量以及取代基的差异会影响它们的抗癌活性。这些信息可能有助于评估其他人参皂苷及其苷元的结构/功能关系，并有助于开发新型抗癌药物。
