Glucose Uptake-Stimulating Metabolites from Aerial Parts of Centaurea sicula

Abstract

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).Centaurea is one of the most emblematic plant genera of the Mediterranean area, and with its hundreds of species (between 500 and 700, depending on the classification used), it is among the most numerous and taxonomically complex in the Cardueae tribe of the Asteraceae family. Centaurea plants can be annual, biennial, or perennial, rarely dwarf shrubs, with usually unarmed leaves. Along with the Iranian region, the Mediterranean area is one of the hotspots of distribution of the genus. 1−5 Considering this botanical richness, it is not surprising that several Centaurea species have long been used in folk medicine for a variety of ailments, such as treatment of diabetes, diarrhea, hypertension, headache, muscle pains, microbial infections, rheumatism, and malaria. 6 Compounds virtually belonging to dozens of classes of secondary metabolites have been characterized in Centaurea species, but, undoubtedly, sesquiterpene lactones, 7,8 flavonoids, 9 and alkaloids 10 are the hallmark of this genus.Centaurea sicula L. is a Mediterranean species distributed in Spain, Southern Italy, Malta, Tunisia, and other countries of Northwestern Africa. 11 In Sicily, the Italian region that gives the name to the species, it is widespread in the uncultivated lands. 12 Previous phytochemical investigations on this plant have reported the occurrence of sesquiterpene lactones, 13,14 flavonoids, 15 acetylenes, 16 and its essential oil composition. 17 Recently, the antioxidant properties of the plant extracts of specimens collected in Tunisia have been investigated. 18 In the frame of our research project aimed at the phytochemical profiling of species of the genus Centaur-