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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-D-glucopyranose,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 IC 50  values of 7.0 and 7.5 μg/mL, respectively. ß-D-glucopyranose,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.

Constituents ofTalisia nervosawith Potential Utility against Metabolic Syndrome