Muscari comosum L.: the ancient wild plant protagonist of the Mediterranean diet and its effects on liver cancer cells.

Among the wild plants that grow throughout the Mediterranean area including Basilicata, particular attention was paid to Leopoldia comosa L. (syn. Muscari comosum L.), a spontaneous plant belonging to the Asparagaceae family known for its therapeutic effect known in folk medicine [1]. We investigated the effects on HepG2 hepatoma cells of Muscari comosum aqueous and methanol extracts. The metabolomics analysis performed by NMR suggested that M. comosum extracts modify the intra­ and extra­cellular metabolic profile. Moreover, the extracts exhibited concentration/solvent dependent radical scavenging activity, as well as promotion of Nrf2 expression which, in turn and in different way, modulated the expression level of downstream target genes SOD­2, GPX­1. Several ATP binding cassette (ABC) transporters are Nrf2 targets. The extracts promote the expression of ABCC6 and ABCG2, two ATP dependent transporters involved in chemotherapy, multidrug resistance and also responsible for glutathione transport [2]. The increase in ROS is responsible for blocking the cell cycle and the reduction of cell viability. ROS levels increased at higher concentration of the extracts. Depending on the extract, p21cip1/waf1 expression level increased in p53­independent or ­dependent manner. Over­expression of p53 protein plays a key role in activating the intrinsic pathway of apoptosis. Treatment with M. comosum extracts increased the expression level of cytochrome c as well as downregulated GRP78/BiP and upregulated CHOP, involved in the unfolded protein response (URP) and, consequently, in ER­stress.