Diterpenoid, steroid, and triterpenoid agonists of liver X receptors from diversified terrestrial plants and marine sources.
Journal Article (Journal Article)
It has been demonstrated that liver X receptors (LXR) play a significant role in cholesterol homeostasis. Agonists of LXR are expected to increase cellular cholesterol efflux, lower LDL, and raise HDL levels. Screening of a natural product library of plant extracts using a LXR-SPA binding assay and bioassay-guided fractionation of a number of plant and marine gorgonian extracts led to the isolation of a number of active compounds. These included acanthoic acid (1) and alcohol (2), viperidone (3), polycarpol (4), rosacea acid (5), a cycloartane derivative (6), a new cycloartane analogue (7), betulinic acid (8), and gorgostane derivatives (9, 10, and 11). Of these compounds, 1, 4, and 11 exhibited potent binding affinity for alpha-receptor with IC(50) values of 0.25, 0.12, and 0.07 microM, respectively. Functionally they also showed strong coactivator association stimulation for LXRalpha receptor with EC50 values of 0.18, 0.03, and 0.05 microM, respectively. They also exhibited 15-, 8-, and 13-fold induction of the alpha-receptor in a transactivation assay in HEK-293 cells, respectively. In general these compounds were selective for the LXR alpha-receptor over the beta-receptor in all assays and were much better stimulators of the alpha-receptor than the endogenous steroid ligands.
Full Text
Duke Authors
Cited Authors
- Jayasuriya, H; Herath, KB; Ondeyka, JG; Guan, Z; Borris, RP; Tiwari, S; de Jong, W; Chavez, F; Moss, J; Stevenson, DW; Beck, HT; Slattery, M; Zamora, N; Schulman, M; Ali, A; Sharma, N; MacNaul, K; Hayes, N; Menke, JG; Singh, SB
Published Date
- August 2005
Published In
Volume / Issue
- 68 / 8
Start / End Page
- 1247 - 1252
PubMed ID
- 16124770
International Standard Serial Number (ISSN)
- 0163-3864
Digital Object Identifier (DOI)
- 10.1021/np050182g
Language
- eng
Conference Location
- United States