Bioactive triterpenoids from the caffeine-rich plants guayusa and maté.

Unlike all other caffeinated plants, guayusa (Ilex guayusa Loes.) and maté (Ilex paraguariensis A. St. Hill) contain high amounts of pentacyclic triterpenoid acids and alcohols. A phytochemical investigation on these plants revealed a similar triterpenoid profile and a content of ursolic acid (0.7-1%) and amyrin esters (up to 0.5%), quite unusual for dietary plants. The major constituent of the amyrin complex from both plants is α-amyrin palmitate (2a), accompanied by lower amounts of its corresponding palmitoleate (2b) and by the corresponding constitutional isomers from the ß-series (3a and 3b, respectively). Ursolic acid (1) was identified as the responsible for the activity of maté and guayusa extracts in the activation of TGR5, a nuclear receptor of relevance for the prevention and management of diabetes and metabolic syndrome because of its involvement in the regulation of energy expenditure and insulin sensitivity.

Stearoyl-CoA-desaturase 1 regulates lung cancer stemness via stabilization and nuclear localization of YAP/TAZ.

This corrects the article DOI: 10.1038/onc.2017.75.

Stearoyl-CoA-desaturase 1 regulates lung cancer stemness via stabilization and nuclear localization of YAP/TAZ.

Recent evidences suggest that stearoyl-CoA-desaturase 1 (SCD1), the enzyme involved in monounsaturated fatty acids synthesis, has a role in several cancers. We previously demonstrated that SCD1 is important in lung cancer stem cells survival and propagation. In this article, we first show, using primary cell cultures from human lung adenocarcinoma, that the effectors of the Hippo pathway, Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), are required for the generation of lung cancer three-dimensional cultures and that SCD1 knock down and pharmacological inhibition both decrease expression, nuclear localization and transcriptional activity of YAP and TAZ. Regulation of YAP/TAZ by SCD1 is at least in part dependent upon ß-catenin pathway activity, as YAP/TAZ downregulation induced by SCD1 blockade can be rescued by the addition of exogenous wnt3a ligand. In addition, SCD1 activation of nuclear YAP/TAZ requires inactivation of the ß-catenin destruction complex. In line with the in vitro findings, immunohistochemistry analysis of lung adenocarcinoma samples showed that expression levels of SCD1 co-vary with those of ß-catenin and YAP/TAZ. Mining available gene expression data sets allowed to observe that high co-expression levels of SCD1, ß-catenin, YAP/TAZ and downstream targets have a strong negative prognostic value in lung adenocarcinoma. Finally, bioinformatics analyses directed to identify which gene combinations had synergistic effects on clinical outcome in lung cancer showed that poor survival is associated with high co-expression of SCD1, ß-catenin and the YAP/TAZ downstream target birc5. In summary, our data demonstrate for the first time the involvement of SCD1 in the regulation of the Hippo pathway in lung cancer, and point to fatty acids metabolism as a key regulator of lung cancer stem cells.

Cannabinoids: occurrence and medicinal chemistry.

With an inventory of several hundreds secondary metabolites identified, Cannabis sativa L. (hemp) is one of the phytochemically best characterized plant species. The biomedical relevance of hemp undoubtedly underlies the wealth of data on its constituents and their biological activities, and cannabinoids, a class of unique meroterpenoids derived from the alkylation of an olivetollike alkyl resorcinol with a monoterpene unit, are the most typical constituents of Cannabis. In addition to the well-known psychotropic properties of Δ(9)-THC, cannabinoids have been reported to show potential in various fields of medicine, with the capacity to address unmet needs like the relief of chemotherapy-derived nausea and anorexia, and symptomatic mitigation of multiple sclerosis. Many of the potential therapeutic uses of cannabinoids are related to the interaction with (at least) two cannabinoid G-protein coupled receptors (CB1 and CB2). However, a number of activities, like the antibacterial or the antitumor properties are non totally dependent or fully independent from the interaction with these proteins. These pharmacological activities are particularly interesting since, in principle, they could be easily dissociated by the unwanted psychotropic effects. This review aims at giving readers a survey of the more recent advances in both phytochemistry of C. sativa, the medicinal chemistry of cannabinoids, and their distribution in plants, highlighting the impact that research in these hot fields could have for modern medicinal chemistry and pharmacology.

The flavonoids of leek, Allium porrum.

A phytochemical investigation of the extracts obtained from bulbs of leek. Allium porrum L. has led to the isolation of five flavonoid glycosides based on the kaempferol aglycone. Two of them are new compounds and have been identified as kaempferol 3-O-[2-O-(trans-3-methoxy-4-hydroxycinnamoyl)-beta-D-galactopyranosyl]-(1-->4)-O-beta-D-glucopyranoside, and kaempferol 3-O-[2-O-(trans-3-methoxy-4-hydroxycinnamoyl)-beta-D-glucopyranosyl]-(1-->6)-O-beta-D-glucopyranoside, on the basis of spectroscopic methods, including 2D NMR. The isolated compounds have been evaluated for their human platelet anti-aggregation activity.

Kaempferide triglycoside: a possible factor of resistance of carnation (Dianthus caryophyllus) to Fusarium oxysporum f. sp. dianthi.

A kaempferide triglycoside has been found as a constitutive component in an uninfected carnation (Dianthus caryophyllus) of the cultivar Novada. The chemical structure has been determined mainly by the use of spectroscopic methods, including 2D NMR experiments. It showed a strong activity in restricting fungal parasite development, which could contribute to the known ability of carnation cv. Novada to resist to Fusarium oxysporum f. sp. dianthi infection.

Cytotoxic saponins from bulbs of Allium porrum L.

An extensive phytochemical analysis of the saponin content has been undertaken on leek, Allium porrum L., sown and collected at different seasons. As a result of this investigation, eight saponins (1-8) have been isolated, four of them (5-8) being novel compounds. Compounds 5 and 6, possessing the same tetrasaccharide moiety of compounds 1 and 3, display very unusual spirostane aglycones, 12-ketoporrigenin and 2,12-diketoporrigenin (named porrigenin C), respectively, recently isolated for the first time as free sapogenin in the same plant. Compounds 7 and 8 are rare cholestane bidesmosides possessing a di- and trisaccharide residues linked to a polyhydroxycholesterol aglycone, respectively. The structures of the isolated compounds have been determined by nondegradative spectroscopic analysis, mainly based on NMR. All the eight saponins isolated from leek were tested for their cytotoxic activity against two different cell lines in vitro, and compounds 1, 2, and 6 resulted particularly active.

Novel betaines from the marine sponge Agelas dispar.

Three novel betaine alkaloids, called aminozooanemonin (1), pyridinebetaine A (2), and pyridinebetaine B (3), have been isolated from the Caribbean sponge Agelas dispar. Their structures were determined by FABMS, IR, UV, and 1D and 2D NMR spectroscopic experiments. Aminozooanemonin and pyridinebetaine A showed moderate antibacterial activity.

Novel bromopyrrole alkaloids from the sponge Agelas dispar.

Further investigation of the Caribbean marine sponge Agelas dispar for biologically active constituents has led to the isolation of the novel bromopyrrole alkaloids longamide B (1), and clathramides C (2) and D (3), whose structures have been determined by spectroscopic methods. Isolation of the known keramadine (4) and of the ecdysonic sterols ecdysterone (5) and ajugasterone C (6) is also reported. The antimicrobial activities of the isolated bromopyrrole alkaloids is summarized.