Abstract
Analysis of Verdicchio (a white wine produced in Italy) with high performance liquid chromatography-tandem mass spectrometry (HPLC-ESI-MS-MS) showed a concentration of ethyl caffeoate (CfE), a natural phenolic substance, of 67.3 μmol L-1; CfE was then purified from wine with preparative reversed phase HPLC and tested on rat hepatic stellate cell cultures (HSC). HSC proliferation induced by iron(III) nitrilotriacetate (FeNTA), a pro-oxidant agent (absorbance = 0.68 ± 0.03 versus 0.32 ± 0.02 in controls), was significantly inhibited by CfE starting at a concentration of 10 μmol L-1 (absorbance = 0.45 ± 0.01), with a maximal effect at 20 μmol L-1 (absorbance = 0.32 ± 0.02). The formation of intracellular hydroperoxides induced by FeNTA was significantly reduced by CfE starting at a concentration of 10 μmol L-1 and completely prevented by CfE at a concentration of 20 μmol L-1. The increase in α1(I) procollagen mRNA synthesis induced by FeNTA was inhibited by CfE starting at a concentration of 10 μmol L-1 and almost completely at a concentration of 20 μmol L-1. Thus, Verdicchio wine is a remarkable source (about seven-fold the bioactive concentration) of CfE, an interesting drug to be tested as an antifibrotic agent. © 2005 Elsevier B.V. All rights reserved.