New Polyacetylenes, DGAT Inhibitors from the Roots of Panax ginseng

Abstract

The petroleum ether extract of Panax ginseng showed a significant inhibition of the diacylglycerol acyltransferase (DGAT) enzyme from rat liver microsomes. Bioactivity-guided fractionation led to the isolation of two new polyacetylenic compounds, (9R,10S)-epoxyheptadecan-4,6-diyn-3-one (1) and 1-methoxy-(9R,10S)-epoxyheptadecan-4,6-diyn-3-one (2). Their chemical structures were elucidated on the basis of spectroscopic evidence and asymmetric synthesis. IC₅₀ values of 9 μg/mL (1) and 32 μg/mL (2) were obtained.

Panax ginseng - Araliaceae - diacylglycerol acyltransferase (DGAT) - polyacetylenes - structure elucidation

References

• 1 Lehner R, Kuksis A. Biosynthesis of triacylglycerols.  Prog Lipid Res. 1996;  35 169-201
• 2 Cases S, Smith S, Zheng Y, Myers H, Lear S R, Sande E. et al . Identification of gene encoding an acyl CoA:diacylglycerol acyltransferase, a key enzyme in triacyglycerol synthesis.  Proc Natl Acad Sci USA. 1998;  95 13 018-23
• 3 Smith S J, Cases S, Jensen D R, Chen H C, Sande E, Tow B. et al . Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking DGAT.  Nat Genet. 2000;  25 87-90
• 4 Jung B S, Shin M K. Encyclopedia of illustrated Korean natural drugs, Araliaceae. In: Kwon SB, editor Seoul; Young Lim Sa. 1998: pp. 439-43
• 5 Hirakura K, Morita M, Nakajima K, Ikeya Y, Mitsuhashi H. Polyacetylenes from the roots of Panax ginseng .  Phytochemistry. 1991;  30 3327-33
• 6 Poplawski J, Wrobel J T, Glinka T. Panaxydol, a new polyacetylenic epoxide from Panax ginseng roots.  Phytochemistry. 1980;  19 1539-41
• 7 Saita T, Matsunaga H, Yamamoto H, Nagumo F, Fujito H, Mori M. et al . A highly sensitive enzyme-linked immunosorbent assay (ELISA) for antitumor polyacetylenic alcohol, panaxytriol.  Biol Pharm Bull. 1994;  17 798-802
• 8 Fujimoto Y, Satoh M. Acetylenes from the callus of Panax ginseng .  Phytochemistry. 1987;  26 2850-2
• 9 Matsunaga H, Katano M, Yamamoto H, Fujito H, Mori M, Takata K. Cytotoxic activity of polyacetylene compounds in Panax ginseng C. A. Meyer.  Chem Pharm Bull. 1990;  38 3480-2
• 10 Wang C N, Shiao Y J, Kuo Y H, Chen C C, Lin Y L. Inducible nitric oxide synthase inhibitors from Saposhnikovia divaricata and Panax quinquefolium .  Planta Med. 2000;  66 644-7
• 11 Kwon B M, Nam J Y, Lee S H, Jeong T S. Isolation of cholesteryl ester transfer protein inhibitors from Panax ginseng roots.  Chem Pharm Bull. 1996;  44 444-5
• 12 Coleman R A. Diacylglycerol acyltransferase and monoacylglycerol acyltransferase from liver and intestine.  Methods Enzymol. 1992;  209 98-103
• 13 Ko J S, Rho M C, Chung M Y, Song H Y, Kang J S, Kim K H. et al . Quinolone alkaloids, diacylglycerol acyltransferase inhibitors from the fruits of Evodia rutaecarpa .  Planta Med. 2002;  68 1131-3
• 14 Bohlmann F, Burkhardt T, Zdero C. Naturally Occurring Acetylenes. London; Academic Press 1973: p. 4