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.

Chemical composition, antifungal and antibiofilm activities of essential oils from Glycyrrhiza foetida (Desf.) growing in Tunisia.

This study was designated to investigate the chemical composition, the antifungal activity and antibiofilm properties of Glycyrrhiza foetida (Desf.) growing in Tunisia and recognized for its pharmacological and therapeutic effects. The chemical analysis of essential oil samples prepared via hydrodistillation of the aerial parts was performed by gas chromatography-mass spectrometry (GC-MS). Moreover, the antifungal activity of G. foetida essential oil was developed against three dermatophyte strains, two molds and Candida spp. yeasts using the broth microdilution assay. According to the percentages, the main constituents are δ-cadinene (13.9%), (E)-caryophyllene (13.2%) and γ-cadinene (8.3%). The efficiency of the essential oil in inhibiting Candida albicans biofilms formation was also evaluated in terms of inhibitory percentages. The results showed that C. albicans and Microsporum canis were the most sensitive to G. foetida essential oil with a complete inhibition at 0.4 and 0.2 mg ml-1 , respectively. Candida albicans biofilm development was reduced by 80% by the volatile oil at a concentration of 0.8 mg ml-1 . The essential oil of G. foetida has a promising role in the control of fungal agents with medical interest and in inhibition of Candida biofilm development.

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.

Metabolite profiling, enzyme inhibitory activity and antioxidant potential of different extracts from Glycyrrhiza foetida Desf. (Fabaceae, Galegeae, Glycyrrhizinae).

Obesity, a risk factor for the development of type 2 diabetes, represents a socio-economic burden for healthcare systems. Consequently multiple studies aiming to facilitate early diagnostic and prevent complications have demonstrated the promising role of phenolic derivatives on diabetes management. In this frame, the present study aimed to establish for the first time the chemical ingredients and to appraise the antioxidant and the enzyme inhibitory properties of Glycyrrhiza foetida aerial parts and roots extracts using methanol, ethyl acetate and chloroform solvents. The phytochemicals were analyzed via (HPLC-MS/MS). In addition, the extracts were tested for inhibitory activities against α-amylase, α-glucosidase, acetylcholinesterase, butyrylcholinesterase, and tyrosinase. The antioxidant capabilities were evaluated using various methods (phospho­molybdenum, DPPH, ABTS, FRAP, CUPRAC, and metal chelating assays). Notably, twenty-nine secondary metabolites, namely eleven phenolic acids, seventeen flavonoids and a non-phenolic acid have been identified. Delphinidin 3,5-diglucoside, rutin, isoquercitrin, hyperoside, catechin, phloridzin and hesperidin were the major compounds in the aerial parts extracts while trans-cinnamic acid was the dominant compound in roots. Among phenolic acids, vanillic acid was found to be the main constituent in all extracts. The tested extracts were found to yield TPC in amounts ranging from 34.08 to 49.36 mg GAE/g and TFC ranging from 7.01 to 45.74 mg RE/g. G. foetida extracts showed interesting in vitro antioxidant properties. Additionally, all extracts showed a significant anti-tyrosinase activity, with inhibition values ranging between 52.84 and 80.34 mg KAE/g. Thus, G. foetida remains an exceptional matrix for further investigations and application in cosmetics and food additives.