Metabolites from Aerial Parts of Glycyrrhiza foetida as Modulators of Targets Related to Metabolic Syndrome.

A detailed phytochemical investigation has been carried out on the aerial parts of G. foetida leading to the isolation of 29 pure compounds, mainly belonging to the amorfrutin and polyphenol classes. Among them, the new amorfrutin N (5) and exiguaflavone L (21) were isolated and their structures elucidated by means of HR-ESIMS and NMR. All the isolated compounds were investigated for modulation of mitochondrial activity and stimulation of glucose uptake via GLUT transporters, two metabolic processes involved in intracellular glucose homeostasis, which, therefore, correlate with the incidence of metabolic syndrome. These experiments revealed that amorfrutins were active on both targets, with amorfrutin M (17) and decarboxyamorfrutin A (2) emerging as mitochondrial stimulators, and amorfrutin 2 (12) as a glucose uptake promoter. However, members of the rich chalcone/flavonoid fraction also proved to contribute to this activity.

Glucose Uptake-Stimulating Metabolites from Aerial Parts of Centaurea sicula.

A comprehensive phytochemical investigation of aerial parts obtained from Centaurea sicula L. led to the isolation of 14 terpenoids (1-14) and nine polyphenols (15-23). The sesquiterpenoid group (1-11) included three structural families, namely, elemanolides (1-6), eudesmanolides (7 and 8), and germacranolides (9-11) with four unreported secondary metabolites (5-8), whose structure has been determined by extensive spectroscopic analysis, including 1D/2D NMR, HR-MS, and chemical conversion. Moreover, an unprecedented alkaloid, named siculamide (24), was structurally characterized, and a possible biogenetic origin was postulated. Inspired by the traditional use of the plant and in the frame of ongoing research on compounds with potential activity on metabolic syndrome, all the isolated compounds were evaluated for their stimulation of glucose uptake, disclosing remarkable activity for dihydrocnicin (10) and the lignan salicifoliol (15).

PPARα/γ-Targeting Amorfrutin Phytocannabinoids from Aerial Parts of Glycyrrhiza foetida.

An LC-MS/MS-guided analysis of the aerial parts of Glycyrrhiza foetida afforded new phenethyl (amorfrutin)- and alkyl (cannabis)-type phytocannabinoids (six and four compounds, respectively). The structural diversity of the new amorfrutins was complemented by the isolation of six known members and the synthesis of analogues modified on the aralkyl moiety. All of the compounds so obtained were assayed for agonist activity on PPARα and PPARγ nuclear receptors. Amorfrutin A (1) showed the highest agonist activity on PPARγ, amorfrutin H (7) selectively targeted PPARα, and amorfrutin E (4) behaved as a dual agonist, with the pentyl analogue of amorfrutin A (11) being inactive. Decarboxyamorfrutin A (2) was cytotoxic, and modifying its phenethyl moiety to a styryl or a phenylethynyl group retained this trait, suggesting an alternative biological scenario for these compounds. The putative binding modes of amorfrutins toward PPARα and PPARγ were obtained by a combined approach of molecular docking and molecular dynamics simulations, which provided insights on the structure-activity relationships of this class of compounds.

Guaiane-rich phytochemical profile of Centaurea kotschyi subsp. persica (Boiss.) Wagenitz and identification of hypoglycaemic metabolites.

Phytochemical investigation of the aerial parts obtained from the Turkish plant Centaurea kotschyi subsp. persica led to the isolation of nine sesquiterpene lactones belonging to the guaiane class, including the undescribed kotschyols A and B, a monoterpene lactone (daphnauranin E), four known lignans (matairesinol, matairesinoside, arctiin and arctigenin) and an undescribed dihydrobenzofuran neolignan (4-O-glucosylcrataegifin A). The structures of these compounds were defined by spectroscopic analysis, including ECD and 1D/2D NMR, and chemical conversion. Spurred from the traditional use of C. kotschyi subsp. persica and previous reports on the activity of its extracts, the isolated compounds were evaluated for their hypoglycaemic activity disclosing the bioactive components.

Salvigenin, a Trimethoxylated Flavone from Achillea Wilhelmsii C. Koch, Exerts Combined Lipid-Lowering and Mitochondrial Stimulatory Effects.

Phytochemical analysis of the Iranian plant Achillea wilhelmsii led to the isolation of 17 pure secondary metabolites belonging to the classes of sesquiterpenoids and phenolics. Two of these compounds, named wilhemsin (7) and wilhelmsolide (9), are new sesquiterpenoids, and the first shows undescribed structural features. Their structures were elucidated through extensive spectroscopic analysis, mainly based on 1D and 2D NMR, and chemical derivatization. Starting from plant traditional use and previous reports on the activity of the plant extracts, all the pure compounds were evaluated on endpoints related to the treatment of metabolic syndrome. The sesquiterpene hanphyllin (8) showed a selective cholesterol-lowering activity (-12.7% at 30 µM), santoflavone (13) stimulated glucose uptake via the GLUT transporter (+16.2% at 30 µM), while the trimethoxylated flavone salvigenin (14) showed a dual activity in decreasing lipid levels (-22.5% palmitic acid biosynthesis at 30 µM) and stimulating mitochondrial functionality (+15.4% at 30 µM). This study further confirms that, in addition to the antioxidants vitexin, isovitexin, and isoschaftoside, A. wilhelmsii extracts contain molecules that can act at different levels on the metabolic syndrome symptoms.