Pentacyclic Triterpenes from Cecropia telenitida Can Function as Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1

Abstract

Plant extracts from the genus Cecropia have been used by Latin-American traditional medicine to treat metabolic disorders and diabetes. Previous results have shown that roots of Cecropia telenitida contain pentacyclic triterpenes and these molecules display a hypoglycemic effect in an insulin-resistant murine model. The pharmacological target of these molecules, however, remains unknown. Several lines of evidence indicate that pentacyclic triterpenes inhibit the 11β-hydroxysteroid dehydrogenase type 1 enzyme, which highlights the potential use of this type of natural product as phytotherapeutic or botanical dietary supplements. The main goal of the study was the evaluation of the inhibitory effect of Cecropia telenitida molecules on 11β-hydroxysteroid dehydrogenase type 1 enzyme activity. A pre-fractionated chemical library was obtained from the roots of Cecropia telenitida using several automated chromatography separation steps and a homogeneous time resolved fluorescence assay was used for the bio-guided isolation of inhibiting molecules. The screening of a chemical library consisting of 125 chemical purified fractions obtained from Cecropia telenitida roots identified one fraction displaying 82% inhibition of the formation of cortisol by the 11β-hydroxysteroid dehydrogenase type 1 enzyme. Furthermore, a molecule displaying IC50 of 0.95 ± 0.09 µM was isolated from this purified fraction and structurally characterized, which confirms that a pentacyclic triterpene scaffold was responsible for the observed inhibition. Our results support the hypothesis that pentacyclic triterpene molecules from Cecropia telenitida can inhibit 11β-hydroxysteroid dehydrogenase type 1 enzyme activity. These findings highlight the potential ethnopharmacological use of plants from the genus Cecropia for the treatment of metabolic disorders and diabetes.

Pentacyclic Triterpene Profile and Its Biosynthetic Pathway in Cecropia telenitida as a Prospective Dietary Supplement

“…All molecules were isolated as described in the extraction process and flash and preparative chromatography section. The 1D 13C-NMR fingerprint for 17.94 min is equal to the previously reported isoyarumic acid [ 16 ]. Additionally, the connectivity was fully determined employing homo- and heteronuclear 2D-NMR experiments (see Supplementary Materials ).…”

“…The automated flash chromatography fractionation of powdered Cecropia telenitida roots [ 16 ] yielded 86 fractions. TLC fingerprinting, using vanillin-sulfuric acid as a derivatizing agent, was carried out to determine the fractions whose chromatographic profile was similar to DE16.…”

“…The powdered roots were extracted using a solvent system composed of dichloromethane (1): ethyl acetate (1) at room temperature (25 °C) and under constant stirring (90 rpm) for 14 days, employing a semi-pilot extraction system designed and manufactured by Process Solutions and Equipment (Bogotá, Colombia). In order to perform the fractionation process, the automated flash chromatography conditions were replicated according to the reported procedure without any modification [ 16 ].…”

“…In a previous report, using in vitro testing, we isolated a fraction from Cecropia telenitida active towards the metabolic target 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The active fraction was codified as DE16 [ 16 ], and part of our initial work was to describe its metabolic PT profile. Interestingly, in the same study, DE16 subfractions were considerably less active than the whole fraction over the selected metabolic target (11β-HSD1), suggesting a synergistic effect.…”

Plants of Genus Mentha: From Farm to Food Factory

“…Medicinal plants represent a significant source of therapeutic remedies, being also the basis of traditional or indigenous healing systems, still widely used by the majority of populations in many countries [ 1 , 2 ]. Recently, the ethnopharmacological potentials of these plant matrices have received important consideration by both scientists and the pharmaceutical industry towards complementing or even replacing conventional pharmacotherapies [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. Moreover, many of these plants have also been highlighted for their added-food value ability, providing a dual role, i.e., food flavor and bioactive compounds [ 3 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ].…”