Arbutus unedo L. Fractions Exhibit Chemotherapeutic Properties for the Treatment of Gastrointestinal Stromal Tumors.

Novel treatments in gastrointestinal stromal tumors (GISTs) are essential due to imatinib resistance and the modest results obtained with multi-target tyrosine kinase inhibitors. We investigated the possibility that the hydroalcoholic extract from the leaves of Arbutus unedo L. (AUN) could harbor novel chemotherapeutics. The bio-guided fractionation of AUN led to a subfraction, FR2-A, that affected the viability of both imatinib-sensitive and -resistant GIST cells. Cells treated with FR2-A were positive for Annexin V staining, a marker of apoptosis. A rapid PARP-1 downregulation was observed, although without the traditional caspase-dependent cleavage. The fractionation of FR2-A produced nine further active subfractions (FRs), indicating that different molecules contributed to the effect promoted by FR2-A. NMR analysis revealed that pyrogallol-bearing compounds, such as gallic acid, gallic acid hexoside, gallocatechin, myricetin hexoside, and trigalloyl-glucose, are the main components of active FRs. Notably, FRs similarly impaired the viability of GIST cells and peripheral blood mononuclear cells (PBMCs), suggesting a non-specific mechanism of action. Nevertheless, despite the lack of specificity, the established FRs showed promising chemotherapeutic properties to broadly affect the viability of GIST cells, including those that are imatinib-resistant, encouraging further studies to investigate whether pyrogallol-bearing compounds could represent an alternative avenue in GISTs.

Saving the local tradition: ethnobotanical survey on the use of plants in Bologna district (Italy).

BACKGROUND: Traditional knowledge about plants is unfortunately subjected to a progressive loss, mainly due to globalization and depopulation of the rural areas. This work enhances the ethnobotanical knowledge from Northern Italy, specifically Bologna district, and contributes to preserving Italy's plant-based traditional knowledge and to valorize local resources also in view of an ecological transition. METHODS: The study was conducted between 2010 and 2016 in Bologna district encompassing 22 municipalities, which were grouped into three areas: hill, mountain, and plain. In total, 1172 key informants were interviewed, ranging in age from 50 to 85 years, and having strong links with traditional activities in the area. RESULTS: The final inventory included 374 taxa belonging to 91 families. Among these, 251 were wild native, 40 wild alien, 74 cultivated and 6 were products bought from the market. Hill, mountain, and plain provided information on 278, 213, and 110 taxa, respectively. The most cited families were Asteraceae, Lamiaceae, and Rosaceae. The information was systematized in 12 use categories (UC): medicinal (MED), food, cosmetic, domestic, superstitious-magical-religious (SMR), agropastoral, craft, repellent-insecticide, veterinary, toxic, games, other uses and information. The most relevant UC were in turn divided into subcategories. A descriptive table with all the results was also created. MED was the most relevant UC (310 taxa), and among the 17 MED subcategories, the most significant ones were: gastroenteric (160 taxa), respiratory (133 taxa), and dermatologic (122 taxa). Food was also relevant (197 taxa, and 16 subcategories), and the widest food subcategory was nutraceutical (98 taxa). In cosmetic, the most relevant subcategory was skin treatment (37 taxa). Within SMR, the majority of the plants were cited to heal a disease in a ritual or superstitious way (15 taxa), while for agropastoral, the majority of the taxa (29) were cited as feed. CONCLUSIONS: The data collected has highlighted a significant traditional use of plants in Bologna district. Some plants or uses emerged for the first time from an ethnobotanical study carried out in Italy. The inclusion of a large number of municipalities and informants enabled the collection of a wide spectrum of data, encompassing various uses, anecdotes, and historical curiosities, which are crucial to preserve from being forgotten.

Metabolomic analysis and bioactivities of Arbutus unedo leaves harvested across the seasons in different natural habitats of Sardinia (Italy).

BACKGROUND: Arbutus unedo L. is a wild tree of Mediterranean regions used as food and in traditional medicine and important for afforestation programs. There is no detailed information available on the variation of A. unedo leaves metabolome across the seasons. The leaves were analyzed by Proton nuclear magnetic resonance (1 H NMR)-based metabolomics, comparing samples harvested across the seasons and in ten different natural habitats of Sardinia (Italy). RESULTS: Multivariate analysis showed the impact of seasonal variation on the metabolome: glucose and quinic acid increased in summer, while in spring sucrose was accumulated. ß-Arbutin, the main known active principle of A. unedo, generally reached the highest concentration in autumn. In winter, O-ß-methylglucose, γ-aminobutyric acid (GABA), flavonols (quercetin-3-O-α-rhamnoside, myricetin-3-O-α-rhamnoside, kaempferol-3-O-α-rhamnoside), catechin, and gallocatechin increased. Characteristic metabolomic features were found also for samples collected in different locations. For instance, trees growing at the highest altitude and exposed to lower temperatures produced less flavonols and catechins. The only sample collected on trees growing on limestones, dolomites, and dolomitic limestones type of soil showed generally the highest content of arbutin. The highest phenolics content was found during spring, while samples collected on flowering branches in winter were the ones with the highest flavonoid content. The antioxidant activity was also variated, ranging from 1.3 to 10.1 mg of Trolox equivalents (TE)/mL of extract, and it was positively correlated to both total phenolics and flavonoid content. Winter samples showed the lowest antibacterial activity, while summer and autumn ones exhibited the highest activity (IC50 values ranging from 17.3 to 42.3 µg/mL against Staphylococcal species). CONCLUSION: This work provides 1 H-NMR fingerprinting of A. unedo leaves, elucidating the main metabolites and their variations during seasons. On the basis of arbutin content, autumn could be considered the balsamic period of this taxon. Samples collected in this season were also the most active ones as antibacterial. Moreover, an interesting metabolomic profile enriched in catechins and flavonols was observed in leaves collected in winter on flowering branches which were endowed with high antioxidant potential.