A pinitol-rich Glycyrrhiza glabra L. leaf extract as functional supplement with potential in the prevention of metabolically induced inflammation and insulin-resistance

Glycyrrhiza glabra L. (Licorice) is a small perennial herb that has been traditionally used to treat many diseases. While liquorice roots have been well studied for their pharmacological activities, less research has been conducted on aerial parts. Leaves represent a good source of the inositol D-pinitol, useful in the treatment of insulin resistance-related pathologies. In this study, a methanolic extract from G. glabra leaves (GGLME) was prepared and profiled for its polyphenols content. The amount of D-pinitol was also measured by HPLC-ELSD and NMR. The extract was then tested, using two different models, for its in vitro protective effects against insulin resistance induced by palmitic acid (PA), the most prevalent saturated free fatty acid in circulation, comparing its activity with D-pinitol. In the first model the activity against endothelial dysfunction in endothelial cells (HUVECs) was evaluated. GGLME restored tyrosine phosphorylation of IRS-1 and downstream PI3K/Akt/eNOS signaling pathway altered by PA. Next, GGLME activity against lipotoxicity-related hypertrophy, inflammation, and insulin resistance in 3T3-L1 adipocytes exposed to PA was evaluated. GGLME pretreatment decreased PA-induced lipid deposition, PPAR-γ and NF-κB pathway, similarly to D-pinitol, and improved insulin sensitivity increasing PI3K, pAkt, and GLUT1 levels. Interestingly, we demonstrated, in both models, that the extract, as well as D-pinitol, possess insulin sensitizing effects since they induced insulin-PI3K/Akt pathway also under basal conditions. This study confirms that liquorice leaves, considered a waste of resource, gives a phytocomplex endowed with potential therapeutic properties and thus could potentially be reused, and support further in vivo studies on animal and human models. In conclusion, liquorice leaves extract represents a potential candidate for prevention of metabolically induced inflammation, frequently leading to metabolic disorders. Moreover, the use of the phytocomplex, rather than a pure compound, allows avoiding a series of isolation/purification procedures and can be easily scaled up for industrial applications.