Nunziatina De Tommasi

Crataegus L. (Rosaceae) comprises several species rich in nutrients and bioactive compounds with nutraceutical relevance. The present study aimed to investigate the polyphenolic profile, antioxidant activity, and in vitro antihyperglycemic-related activity of fruits from 11 Crataegus taxa collected in Western Sicily, a region characterized by a high diversity of this genus. Total polyphenol quantification indicated that, among the tested extracts, Crataegus laciniata exhibited the highest content (25.54 mg GAE/g). Using high-resolution Orbitrap Q-Exactive PLUS ESI-MS instrument (Thermo Fisher Scientific, Waltham, MA, USA), a comprehensive phytochemical characterization was performed. Hyperoside quantification revealed that Crataegus aff. insengae, Crataegus zichichii, and Crataegus drepanensis are rich in this bioactive compound (1.47, 1.22, 1.22 mg/g DW). Multivariate analysis, including principal component analysis (PCA), highlighted hyperoside and vitexin as the main contributors to sample differentiation. Additionally, Crataegus laciniata, Crataegus drepanensis, and Crataegus aff. insengae showed the highest antioxidant activity in chemical assays (DPPH, ABTS, and FRAP) and in Caco-2 and H9c2 cell models through the modulation of intracellular reactive oxygen species (ROS). Regarding antihyperglycemic-related activity, Crataegus laciniata, Crataegus azarolus var. azarolus, and Crataegus drepanensis extracts showed the best inhibitory activity against α-glucosidase and α-amylase. Overall, the study highlights the value of Crataegus fruits as sources of bioactive compounds for food and nutraceutical research and supports their further valorization.

Lavandula dentata is a medicinal and aromatic plant rich in specialised secondary metabolites, but the biomedical potential of leaf-surface metabolites recovered from pruning biomass remains poorly investigated. In this study, a pruning-derived leaf-surface extract of L. dentata was obtained by brief acetone immersion followed by n-hexane partitioning. Its chemical profile was investigated by ultra-high-performance liquid chromatography coupled with high-resolution tandem mass spectrometry analysis combined with feature-based molecular networking, which revealed an enrichment in methoxylated flavonoids and pentacyclic triterpenes, including oleanane- and ursane-like derivatives. The biological activity of the extract was evaluated in HCT116 colorectal cancer cells, MDA-MB-231 triple-negative breast cancer cells, and HaCaT keratinocytes. After 24 h treatment, the extract selectively reduced HCT116 cell viability in a concentration-dependent manner, with an IC₅₀ of 27.8 ± 1.049 μg/mL, whereas MDA-MB-231 and HaCaT cells were less sensitive. Mechanistic analyses in HCT116 cells showed increased early and late apoptotic populations, mitochondrial membrane depolarisation, and enhanced cleavage of caspase-9, caspase-3, and PARP. These findings indicate that a chemically profiled L. dentata leaf-surface extract selectively impairs colorectal cancer cell survival by activating mitochondria-mediated apoptosis. The study also supports the valorisation of pruning-derived aromatic plant biomass as a source of bioactive natural products with potential biomedical relevance.

Phytochemical study of Cedrus atlantica aerial parts apolar extract led to the isolation of a new abietane diterpene (1), an abietane diterpene reported for the first time as a genuine natural product (2), 2 new megastigmane glycosides (3–4), and 9 known compounds (5–13), including 7 abietanes. Their structures were elucidated by 1D and 2D NMR spectroscopy and HRMS experiments. The crude extract was then evaluated through a broad screening against both Gram-positive and Gram-negative bacterial strains, with Staphylococcus epidermidis being the only affected microorganism. In a next step, a selection of pure compounds was also investigated, and the diterpene 15-hydroxydehydroabietic acid (15-HDAA) (11) was shown to exhibit detectable antibacterial activity against S. epidermidis. Growth kinetics analysis revealed a clear modulation of bacterial growth at sub-minimum inhibitory concentration (MIC), indicating a measurable physiological impact on the bacterium. This effect, when combined, allows a significant reduction in the effective concentration of ampicillin.

The development of advanced cell culture models has overcome the limitations of conventional monolayer cultures, still doubts remain about the reliability of data obtained using traditional systems, as well as the comparability of results from different models. This is highly relevant to preclinical drug analysis, where in vitro studies determine the fate of molecules. We investigated the molecular mechanisms that regulate the activity of cannabidiolic acid (CBDA) in a 3D model of a glioblastoma cell line, comparing the results with those obtained on a conventional monolayer model of the same cells. CBDA targeted the translation initiation factor EIF2A in both tested models. However, the downstream consequences of the CBDA-EIF2A interaction differed between cells cultured in 3D and 2D, since the biological functions and interactome of EIF2A were found to change significantly. Overall, this study sheds new light on the difficulties associated with comparing results obtained using different in vitro models.

Antimicrobial resistance poses a significant threat to global health, highlighting the urgent need for novel therapeutic agents. Plant-derived compounds are a promising source of antimicrobial compounds. Given their huge structural variability, they putatively operate through a multiplicity of modes of action, interacting with various targets. The implementation of appropriate approaches aimed at reliably describe the molecular mechanism of these compounds, allows identifying promising hits, and new pharmacologically exploitable proteins. Here, we investigated the antimicrobial activity of manool, a diterpene isolated from Salvia officinalis L. (Lamiaceae), against the dental pathogen Streptococcus mutans . Using compound-centric proteomic techniques, we identified ATP-binding cassette (ABC) transporters as key targets of manool. These proteins are involved in nutrient uptake and in bacterial drug resistance. Implementing metabolomics approaches, we showed that manool inhibits ABCs, thereby impairing energy metabolism and delaying bacterial proliferation, and. enhancing the efficacy of the antibiotic kanamycin. Finally, based on the docking and molecular dynamics results we hypothesized that manool is able to interfere with the activity of various ABCs by occupying their ATP binding domain. This is the first time that ABCs have emerged from a completely untargeted approach as proteins responsible for the bioactivity of an antibacterial agent.

Phytopathogenic fungi and bacteria pose a serious threat to global agriculture, leading to significant economic losses and potential health risks. Consequently, the search for natural alternatives to synthetic agrochemicals has garnered increasing scientific attention, with plant extracts emerging as promising environmentally friendly solutions. In this context, the surface extract of Salvia discolor, obtained using dichloromethane, was analyzed for its bioactive potential. Chemical profiling revealed a rich composition of terpenoids and flavonoids. The antimicrobial potential of the ground extract was evaluated against nine phytopathogenic fungi (Alternaria solani, Botrytis cinerea, Colletotrichum lindemuthianum, Fusarium solani, Fusarium oxysporum f. sp. lactucae race 1, Phoma betae, Phaeomoniella chlamydospora, Pythium dissotocum, and Stemphylium sp.), and two phytopathogenic bacteria (Clavibacter michiganesis subsp. michiganesis and Pectobacterium carotovorum subsp. carotovorum), selected from common pathogens of agricultural interest. Complete inhibition of P. chlamydospora at 1000 µg mL⁻¹ and strong activity against P. dissotocum, F. solani and B. cinerea was observed, and low inhibition (C. lindemuthianum and F. oxysporum f. sp. lactucae race 1. However, the extract showed promising results in the post-harvest protection of tomatoes against gray mold. Moderate antibacterial activity was seen against C. michiganensis subsp. michiganensis. These findings indicate that S. discolor extract has the potential to serve as an effective natural crop protection agent, though further optimization may be needed for broader application.

The review is a full report of the sesterterpenoids reported up to now, categorized according to producing organisms and bioactivity. All the data have been implemented in a relational database https://sesterterpenoids.unige.net/.

The phytochemical study of Zanthoxylum rhoifolium apolar and medium polarity stem bark and leaf extracts afforded 29 compounds, including three new sesquiterpenes (1 – 3) and one new α-ionone glycoside (4). All compounds were characterized by means of 1D and 2D NMR and HRESIMS data. Furthermore, a precise structural analysis was performed, employing a combined density functional theory (DFT)/NMR approach to elucidate the compounds configurations. The crude extracts were then tested against a panel of gram-positive and gram-negative bacteria by broth dilution methods to determine their minimal inhibitory concentration. In these experimental conditions, no interesting antimicrobial activity was observed.