Inhibitory Effect of Triterpenoid Saponins from the Leaves of Ilex kudingcha on Aggregated LDL-Induced Lipid Deposition in Macrophages

Abstract

We have investigated the inhibitory effect of triterpenoid saponins from the leaves of Ilex kudingcha C. J. Tseng on aggregated low-density lipoprotein (LDL)-induced lipid deposition in macrophages. A cell-based screening model was initially applied on aggregated LDL (aggLDL)-induced lipid deposition on macrophages to test the inhibitory effects of the 12 triterpenoid saponins from this plant. Eight of these compounds inhibited the formation of foam cells and reduced intracellular total cholesterol and triglyceride contents. Structure–activity relationship analysis showed the essential role of the δ-lactone ring for the biological activity. The promoter action of the OH group at the C-12 position, the number of monosaccharides in the sugar chain and the rhamnose at the terminal of the sugar chain is also discussed.

Key words

Ilex kudingcha - Aquifoliaceae - anti‐atherosclerosis - structure–activity relationship - foam cells - triterpenoid saponins

References

• 1 Huang Z C. Clinical study on the effects of Ilex kudincha on treating 35 cases of hypertension.  Chin J Infor Tradit Chin Med. 1997;  4 25
• 2 Xiang H L, Xu H D, Tian W Y, Tian H. An experimented study on the effect of China Ilex kudincha on hyperlipidemia in mice.  China J Chin Mater. 1994;  19 497-498
• 3 Lusis A L. Atherosclerosis.  Nature. 2000;  407 233-241
• 5 Tang L, Jiang Y, Chang H T, Zhan M B, Peng F T. Triterpene saponins from the leaves of Ilex kudingcha. .  J Nat Prod. 2005;  68 1169-1174
• 6 Ouyang M A, Yang C R, Chen Z L, Wang H Q. Triterpenoid saponins from the leaves of Ilex latifolia.  Phytochemistry. 1997;  45 1501-1505
• 7 Melek F R, Miyase T, Abdel-Khalik S M, Hetta M H, Mahmoud I I. Triterpenoid saponins from Oreopanax guatemalensis.  Phytochemistry. 2002;  60 185-195
• 8 Ouyang M A, Yang C R, Chen Z L, Yang C R. Triterpenoid glycosides from Ilex kudingcha.  Phytochemistry. 1996;  43 441-443
• 9 Zhu Y, Liao H, Xie X, Yuan Y, Lee T S, Wang N, Wang X, Shyy J YJ, Stemerman M B. Oxidized LDL downregulates ATP-binding cassette transporter-1 in human vascular endothelial cells via inhibiting liver X receptor (LXR).  Cardiovasc Res. 2005;  68 425-432
• 10 Yancey P G, Jerome W G. Lysosomal cholesterol derived from mildly oxidized low density lipoprotein is resistant to efflux.  J Lipid Res. 2001;  42 317-327
• 11 Palmer A M, Murphy N, Graham A. Triglyceride-rich lipoproteins inhibit cholesterol efflux to apolipoprotein (apo) A1 from human macrophage foam cells.  Atherosclerosis. 2004;  173 27-38
• 12 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.  J Immunol Methods. 1983;  65 55-63
• 13 Folch J, Lees M, Sloane Stanley G H. A simple method for the isolation and purification of total lipids from animal tissues.  J Biol Chem. 1957;  226 497-509
• 14 Nishimura K, Toshiyuki F, Miyase T, Noguchi H, Chen X M. Activity-guided isolation of triterpenoid acyl CoA cholesteryl acyl transferase (ACAT) inhibitors from Ilex kudincha.  J Nat Prod. 1999;  62 1061-1064