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 PPAR, but had no effect on PPAR. Compounds 2-4 activated PPAR, PPAR and LXR. Interestingly, 2 was stronger than 3 towards all three targets. Methyl gallate (2) showed the most potent effect toward both PPAR and PPAR 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-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.

A Multitarget Approach to Evaluate the Efficacy of Aquilaria sinensis Flower Extract against Metabolic Syndrome

“…These results suggest that AF can antagonize the undesired side effect of a full PPARγ agonist and may prevent adipogenesis and the accumulation of cytoplasmic lipid droplets during the differentiation in 3T3-L1 cells. These findings are similar to dual agonists previously reported by us and others [7,[40][41][42] and suggest that AF may have the potential for its use against obesity.…”

“…PPARγ full agonists induce adipogenesis and enhance differentiation of preadipocytes to mature adipocytes [39]. We have previously shown the antiadipogenic effects of selected medicinal plants (T. nervosa, T. hirsuta and T. chebula) and phytochemicals (gallotannins) that possess the property of dual PPAR agonists [7,40,41]. Due to the observed dual agonistic effects of AF, we further evaluated its effect on adipogenesis and lipid accumulation in mature adipocytes.…”

“…In numerous studies, phytochemicals belonging to polyphenols and flavonoids have been found to improve metabolic syndrome through their beneficial effects against lipid accumulation, high blood pressure and increased blood glucose [3,4]. A number of medicinal plants have also been reported to exhibit promising effects against metabolic syndrome due to their antidiabetic, hypolipidemic and anti-obesity effects [5][6][7][8][9]. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that belong to the family of ligand-inducible transcription factors, mainly expressed in three isoforms (PPAR α, β/δ and γ).…”

Natural Products Targeting Liver X Receptors or Farnesoid X Receptor

“…Methyl gallate (88) and ethyl gallate (89) were isolated from Talisia nervosa Radlk, widespread in the tropical moist and wet forest. The evaluation of LXRα transcriptional activity showed that 88 and 89 were 3.16- and 2.62-fold activation of LXRα at a concentration of 100 µg/ml, indicating their potential utility against metabolic syndrome ( Vásqueza et al, 2019 ).…”

Natural Compounds for the Prevention and Treatment of Cardiovascular and Neurodegenerative Diseases

“…In vitro assays on HepG2 revealed that while (–)-catechin activated only PPARγ and not PPARα, the other three compounds activated PPARα, PPARγ and LXR, with methyl gallate being more potent than ethyl gallate on all three targets. The two gallates also reduced nitric oxide (NO) production in mouse macrophages (RAW 264.7) cells [ 71 ].…”