The 2009 ASHS Annual Conference

Folkloric use of medicinal plants continues to be practiced. Oftentimes, knowledge on the therapeutic property of the plant is from traditional practice, and without regard to the bioactive constituents.  For example, members of the genus Vaccinium have been traditionally used for the treatment of diabetic symptoms.  Several phenolic compounds in Vaccinium species are reported as “active constituents.”  Our studies have identified, by gas chromatography-mass spectrometry, phenolic compounds belonging to the group stilbene in Vaccinium berries. Specifically, among the phenolics tested in H4IIEC3 cells, pterostilbene demonstrated the greatest activation of PPAR_ (a transcription factor predominantly involved in fatty acid and lipid catabolism and import, and the activation of genes involved in fatty acid oxidation).  Cathechin and epicatechin, also reported as bioactive constituents in Vaccinium species, showed very weak activation of PPAR_.  Docking studies in the PPAR_ ligand-binding domain supported results obtained in vitro.  Hypercholesterolemic rats fed with diet supplemented with pterostilbene showed decreased serum lipid and glucose levels, in agreement with the role of pterostilbene as PPAR__agonist.  In another study, stilbenes were tested for inhibition of HT-29 colon cancer cell growth.  Cis- and trans-stilbene analogs were synthesized for structure-activity relationship studies. Three cis-isomers that showed the greatest inhibitory activity, together with their corresponding trans-isomers, were tested in vivo using Severe Combined Immunodeficiency (SCID) mice.  In this test, trans-resveratrol trimethylether reduced tumor weight and volume greater than the cis-isomer, opposite that observed in vitro.  The three (of the 6) stilbenes that showed reduction of tumor burden in SCID mice were detected in the serum, suggesting that bioavailability of the compounds play a role in the observed effects.  These studies illustrate the importance of identifying “the relevant” bioactive compound(s) for the therapeutic use of interest in developing sustainable medicinal plant programs.