In this study, Mentha pulegium leaves and flowers harvested in three different Sicilian areas were investigated from a micromorphological, phytochemical and biological point of view. Light and scanning electron microscopy showed the presence of spherocrystalline masses of diosmin both in the leaf epidermal cells and in thin flower petals. Two different chemotypes were identified (I, kaempferide/rosmarinic acid; II, jaceidin isomer A). Phytochemical screening identified plant from collection site II as the richest in total phenolics (16.74 g GAE/100 g DE) and that from collection site I as the richest in flavonoids (46.56 g RE/100 g DE). Seventy-seven metabolites were identified both in flower and leaf extracts. Plant from site II showed the best antioxidant (0.90–83.72 µg/mL) and anti-inflammatory (27.44–196.31 µg/mL) activity expressed as half-maximal inhibitory concentration (IC₅₀) evaluated by DPPH, TEAC, FRAP, ORAC, BSA denaturation and protease inhibition assays. These data were also corroborated by in vitro cell-based assays on lymphocytes and erythrocytes. Moreover, plant of site II showed the best antiangiogenic properties (IC₅₀ 33.43–33.60 µg/mL) in vivo on a chick chorioallantoic membrane. In conclusion, pedoclimatic conditions influence the chemotype and the biological activity of M. pulegium, with chemotype I showing the most promising biological properties.

Alnus glutinosa (namely black alder or European alder) is a tree of the Betulaceae family widely spread through Europe, Southeastern Asia, the Caucasus mountains, and Western Siberia. Its bark is traditionally used for medicinal purposes as an astringent, cathartic, febrifuge, emetic, hemostatic, and tonic, suggesting that it may contain bioactive compounds useful to counteract inflammation. The aim of this study was to investigate the phytochemical profile of A. glutinosa stem bark extract (AGE) by LC-DAD-ESI-MS/MS analysis and to validate some biological activities such as antioxidant, anti-inflammatory and anti-angiogenic properties by in vitro and in vivo models (chick chorioallantoic membranes and zebrafish embryos), that can justify its use against inflammatory-based diseases. The AGE showed a high total phenols content expressed as gallic acid equivalents (0.71 g GAE/g of AGE). Diarylheptanoids have been identified as the predominant compounds (0.65 g/g of AGE) with oregonin, which alone constitutes 74.67% of the AGE. The AGE showed a strong and concentration-dependent antioxidant (IC₅₀ 0.15–12.21 µg/mL) and anti-inflammatory (IC₅₀ 5.47–12.97 µg/mL) activity. Furthermore, it showed promising anti-angiogenic activity, inhibiting both the vessel growth (IC₅₀ 23.39 µg/egg) and the release of an endogenous phosphatase alkaline enzyme (IC₅₀ 44.24 µg/embryo). In conclusion, AGE is a promising source of antioxidant, anti-inflammatory and angio-modulator compounds.

Morin (MRN) is a natural compound with antiangiogenic, antioxidant, anti-inflammatory, and anticancer activity. However, it shows a very low water solubility (28 μg/mL) that reduces its oral absorption, making bioavailability low and unpredictable. To improve MRN solubility and positively affect its biological activity, particularly its antiangiogenic activity, in this work, we prepared the inclusion complexes of MNR with sulfobutylether-β-cyclodextrin (SBE-β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD). The inclusion complexes obtained by the freeze-drying method were extensively characterized in solution (phase-solubility studies, UV–Vis titration, and NMR spectroscopy) and in the solid state (TGA, DSC, and WAXD analysis). The complexation significantly increased the water solubility by about 100 times for MRN/HP-β-CD and 115 times for MRN/SBE-β-CD. Furthermore, quantitative dissolution of the complexes was observed within 60 min, whilst 1% of the free drug dissolved in the same experimental time. ¹H NMR and UV–Vis titration studies demonstrated both CDs well include the benzoyl moiety of the drug. Additionally, SBE-β-CD could interact with the cinnamoyl moiety of MRN too. The complexes are stable in solution, showing a high value of association constant, that is, 3380 M⁻¹ for MRN/HP-β-CD and 2870 M⁻¹ for MRN/SBE-β-CD. In vivo biological studies on chick embryo chorioallantoic membrane (CAM) and zebrafish embryo models demonstrated the high biocompatibility of the inclusion complexes and the effective increase in antiangiogenic activity of complexed MRN with respect to the free drug.

Transition metal complexes have continued to constitute an appealing class of medicinal compounds since the exceptional discovery of cisplatin in the late 1960s. Pt(II)-based complexes are endowed with a broad range of biological properties, which are mainly exerted by targeting DNA. In this study, we report a significant biological investigation into and computation analyses of four Pt(II)-complexes, namely, LDP-1–4, synthesized and characterized according to previously reported procedures. Molecular-modelling studies highlighted that the top two LDP compounds (i.e., LDP-1 and LDP-4) might bind to both matched and mismatched base pair sites of the oligonucleotide 5′-(dCGGAAATTACCG)₂-3′, supporting their anticancer potential. These two complexes displayed noteworthy cytotoxicity in vitro (sub-micromolar–micromolar range) against two leukaemia cell lines, i.e., CCRF-CEM and its multi-drug-resistant counterpart CEM/ADR5000, and remarkable anti-angiogenic properties (in the sub-micromolar range) evaluated in an in vivo model, i.e., a chick embryo chorioallantoic membrane (CAM) assay.

Tyrosinase (EC 1.14.18.1) is implicated in melanin production in various organisms. There is a growing body of evidence suggesting that the overproduction of melanin might be related to several skin pigmentation disorders as well as neurodegenerative processes in Parkinson’s disease. Based on this consideration, the development of tyrosinase inhibitors represents a new challenge to identify new agents in pharmaceutical and cosmetic applications. With the goal of identifying tyrosinase inhibitors from a synthetic source, we employed a cheap and facile preliminary assay using tyrosinase from Agaricus bisporus (AbTYR). We have previously demonstrated that the 4-fluorobenzyl moiety might be effective in interactions with the catalytic site of AbTYR; moreover, the additional chlorine atom exerted beneficial effects in enhancing inhibitory activity. Therefore, we planned the synthesis of new small compounds in which we incorporated the 3-chloro-4-fluorophenyl fragment into distinct chemotypes that revealed the ability to establish profitable contact with the AbTYR catalytic site. Our results confirmed that the presence of this fragment is an important structural feature to improve the AbTYR inhibition in these new chemotypes as well. Furthermore, docking analysis supported the best activity of the selected studied compounds, possessing higher potency when compared with reference compounds.

Cynara cardunculus L. subsp. cardunculus (Cynara cardunculus L. var. sylvestris (Lam.) Fiori), the wild cardoon, is known for its culinary applications and potential health benefits. Due to this, and given the growing interest in circular economies, deepening our under-standing of the effects of wild cardoon leaf waste on angiogenesis and collagenase activity represents a valuable opportunity to valorise agricultural byproducts as health-promoting ingredients. In this study, the waste product of wild cardoon leaves was extracted to examine its chemical composition and biological activities. Analytical techniques identified several bioactive compounds, including flavonoids, hydroxycinnamic acids such as dicaffeoyl-succinoylquinic acids, and luteolin-7-O-rutinoside. In vivo tests in zebrafish embryos and the chick chorioallantoic membrane demonstrated dose-dependent antiangiogenic effects, particularly enhanced by the complexation with hydroxypropyl-β-cyclodextrin (HP-β-CD). Considering the link between angiogenesis and collagenase, the potential effects of the extract on collagenase activity was investigated. The extract alone inhibited collagenase with an IC₅₀ value comparable to that of the standard inhibitor while its complexed form exhibited a 4.5-fold greater inhibitory activity. A molecular docking study examined the interaction between the main compounds and collagenase. In conclusion, wild cardoon leaves can represent a valuable source of bioactive compounds. This study demonstrated that the complexation of the extract with cyclodextrin determines an increase in its biological activity.