Constituents of talisia nervosa with potential utility against metabolic syndrome

Abstract

This study is focused on the isolation and characterization of bioactive secondary metabolites from the ethanolic extract of stems of the Panamanian plant Talisia nervosa Radlk, through a series of target-based cellular assays related to the metabolic syndrome (MetS): A combination of type 2 Diabetes Mellitus (T2DM), hypercholesterolemia, inflammation, and obesity. Bioassay guided fractionation allowed the isolation of four known compounds: (-)-catechin (1), methyl gallate (2), ethyl gallate (3), and ß-D-glucopyranose,1,4,6-tris(3,4,5-trihydroxybenzoate) (4). This is the first report of (-)-catechin (1) and ß-Dglucopyranose, 1,4,6-tris (3,4,5-trihydroxybenzoate) (4) from T. nervosa. Among the isolates, 1 activated PPARγ, but had no effect on PPARα. Compounds 2 - 4 activated PPARα, PPARγ and LXR. Interestingly, 2 was stronger than 3 towards all three targets. Methyl gallate (2) showed the most potent effect toward both PPARα and PPARγ with an increase of 3.0 and 13-fold, respectively, while 4 was most potent in activating LXR with a fold induction of 5.3 at concentrations of 100 μg/mL. The nitric oxide (NO) production was reduced by compounds 2 and 3 with IC50 values of 7.0 and 7.5 μg/mL, respectively. ß-Dglucopyranose, 1,4,6-tris (3,4,5-trihydroxybenzoate) (4) did not cause a significant increase in adipogenesis despite its strong PPARγ agonistic action (8.6-fold increase) and may represent a good candidate for the treatment of MetS without the undesirable side effect of weight gain.