Liver X receptor and peroxisome proliferator-activated receptor agonist from Cornus alternifolia

• Published in: Biochimica et biophysica acta 2012-07, Vol.1820 (7), p.1021-1026
• Main Authors: He, Yang-Qing, Ma, Guo-Yi, Peng, Jiang-nan, Ma, Zhan-Ying, Hamann, Mark T.
• Format: Article
• Language: English
• Subjects: agonists; Animals; Cell Proliferation - drug effects; CHO Cells; cholesterol; Cornus - chemistry; Cornus alternifolia; Cricetinae; Hep G2 Cells; high performance liquid chromatography; homeostasis; hormone receptors; Humans; hydrolysis; Iridoid glycosides; Iridoid Glycosides - chemistry; Iridoid Glycosides - pharmacology; iridoids; leaves; ligands; liver; Liver X Receptors; medicinal plants; Orphan Nuclear Receptors - agonists; Peroxisome proliferator-activated receptors; Peroxisome Proliferator-Activated Receptors - agonists; Plant Extracts - chemistry; Plant Extracts - pharmacology; receptors; screening; spectral analysis; transcription factors
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2012.02.004

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptors superfamily and are transcription factors activated by specific ligands. Liver X receptors (LXR) belong to the nuclear hormone receptors and have been shown to play an important role in cholesterol homeostasis. From the previous screening of several medicinal plants for potential partial PPARγ agonists, the extracts of Cornus alternifolia were found to exhibit promising bioactivity. In this paper, we report the isolation and structural elucidation of four new compounds and their potential as ligands for PPAR. The new compounds were extracted from the leaves of C. alternifolia and fractionated by high-performance liquid chromatography. Their structures were elucidated on the basis of spectroscopic evidence and analysis of their hydrolysis products. Three new iridoid glycosides including an iridolactone, alternosides A–C (1–3), a new megastigmane glycoside, cornalternoside (4) and 10 known compounds, were obtained from the leaves of C. alternifolia. Kaempferol-3-O-β-glucopyranoside (5) exhibited potent agonistic activities for PPARα, PPARγ and LXR with EC50 values of 0.62, 3.0 and 1.8μM, respectively. We isolated four new and ten known compounds from C. alternifolia, and one known compound showed agonistic activities for PPARα, PPARγ and LXR. Compound 1 is the first example of a naturally occurring iridoid glycoside containing a β-glucopyranoside moiety at C-6. ►The metabolites isolated show potential active agonists for PPAR and LXR receptors. ►Four new natural products 1–4 were isolated from the leaves of Cornus alternifolia. ►Metabolite 1 is the first iridoid glycoside containing a β-glucopyranoside at C-6. ►Metabolite 5 showed potent agonistic activities for PPARα, PPARγ and LXR. ►The results presented can be used for further synthetic and pharmacological studies.