Isolation, structural determination, and evaluation of the biological activity of 20(S)-25-methoxyl-dammarane-3beta, 12beta, 20-triol [20(S)-25-OCH3-PPD], a novel natural product from Panax notoginseng.

Abstract

Ginseng has been used extensively for medicinal purposes, with suggested utility for indications as diverse as diabetes, cardiovascular disease and cancer. Herein we report the discovery and characterization of 20(S)-25-OCH3-PPD, a ginsenoside that inhibits growth and survival of cancer cells. The novel dammarane triterpene sapogenin (C31H56O4; molecular weight 492) was isolated from the total hydrolyzed saponins extracted from the leaves of Panax notoginseng using conventional and reverse-phase silica gel chromatography. Based on physicochemical characteristics and NMR data, the compound was identified as 20(S)-25-OCH3-PPD. The biological activities of 20(S)-25-OCH3-PPD and its known analogs, 20(S)-PPD and Rg3, were evaluated in 12 human cancer cell lines. In all cell lines, the order of cytotoxicity of the test compounds was 20(S)-25-OCH3-PPD >> 20(S)-PPD >> Rg3. 20(S)-25-OCH3-PPD also induced apoptosis and cell cycle arrest in the G1 phase, and inhibited proliferation in breast cancer cell lines, demonstrating its potent biological effects. In regard to cytotoxicity, the IC50 values of 20(S)-25-OCH3-PPD for most cell lines were in the lower microM range, a 5-15-fold greater cytotoxicity relative to 20(S)-PPD and a 10-100-fold increase over Rg3. These findings suggest a structure-activity relationship among dammarane-type sapogenins. The data presented here may provide a basis for the future development of 20(S)-25-OCH3-PPD as a novel anti-cancer agent.

• Authors: Y Zhao, W Wang, L Han, E R Rayburn, D L Hill, H Wang, R Zhang
• Journal: Medicinal chemistry (Shariqah (United Arab Emirates)) (Med Chem) Vol. 3 Issue 1 Pg. 51-60 (Jan 2007) ISSN: 1573-4064 [Print] Netherlands
• PMID: 17266624 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 25-methoxydammarane-3,12,20-triol
• Antineoplastic Agents, Phytogenic
• Ginsenosides
• Plant Extracts
• Triterpenes

Topics

• Antineoplastic Agents, Phytogenic (chemistry, isolation & purification, pharmacology)
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• G1 Phase (drug effects)
• Ginsenosides (chemistry, isolation & purification, pharmacology)
• Humans
• Magnetic Resonance Spectroscopy
• Molecular Conformation
• Panax (chemistry)
• Plant Extracts (chemistry)
• Plant Leaves (chemistry)
• Triterpenes (chemistry, isolation & purification, pharmacology)