Cholesterol-lowering effects of piceatannol, a stilbene from wine, using untargeted metabolomics

- Piceatannol lowered total blood cholesterols, LDL-C levels and atherogenic index.
- Piceatannol attenuated esterified fatty acids, lysophospholipids and bile acids.
- Piceatannol raised ratio of esterified arachidonic acid to di-homo-γ linoleic acid.
- High fat diet increased secondary and conjugated bile acids.
- Piceatannol lowered primary and secondary bile acids, raised conjugated bile acids.

This study aims at examining the hypolipidemic effect of piceatannol on high fat diet (HFD)-induced hypercholesterolemic Sprague-Dawley rats and serum metabolite changes. Piceatannol supplement significantly lowered the total cholesterols, low density lipoprotein cholesterol levels and the atherogenic index as compared to the HFD model which only have increased dietary cholesterol intake. Using untargeted mass spectrometry-based metabolomic platforms, multivariate statistics revealed that HFD significantly perturbed fatty acids, lysophospholipids, bile acids and conjugated bile acids. Reduced CYP7A1 protein expression and increase in glycocholate and taurodeoxycholate after piceatannol treatment suggested the conjugated bile acid might contribute to the cholesterol-lowering effect. For lipid profiles, lysoPC (20:2) and lysoPC (20:0) were decreased while the ratio of esterified arachidonic acid to esterified dihomo-γ linoleic acid was up-regulated for rats after piceatannol supplement. These results indicated that the therapeutic effect of piceatannol is associated with bile acid and fatty acid metabolisms and reduced absorption of dietary cholesterols.