A Comparative Study between Lycorine and Galantamine Abilities to Interact with AMYLOID β and Reduce In Vitro Neurotoxicity

Galantamine is a natural alkaloid extracted from the Amaryllidaceae plants and is used as the active ingredient of a drug approved for the treatment of the early stages of Alzheimer's disease. It mainly acts as an acetylcholinesterase (AChE) inhibitor, increasing concentrations of the acetylcholine neurotransmitter. Recent cellular studies have also shown the ability of galantamine to protect SH-SY5Y cell lines against amyloid-beta (A beta)-induced toxicity. Such investigations have supported and validated further in-depth studies for understanding the chemical and molecular features associated with galantamine-protective abilities. In addition to galantamine, other natural alkaloids are known to possess AChE inhibitory activity; among them lycorine has been extensively investigated for its antibacterial, anti-inflammatory and antitumoral activities as well. Despite its interesting biological properties, lycorine's neuroprotective functions against A beta-induced damages have not been explored so far. In this research study, the ability of galantamine and lycorine to suppress A beta-induced in vitro neuronal toxicity was evaluated by investigating the chemical interactions of the two alkaloids with A beta peptide. A multi-technique spectroscopic analysis and cellular cytotoxicity assays were applied to obtain new insights on these molecular associations. The comparison between the behaviors exhibited by the two alkaloids indicates that both compounds possess analogue abilities to interact with the amyloidogenic peptide and protect cells

Functionalized Hyaluronic Acid for “In Situ” Matrix Metalloproteinase Inhibition: A Bioactive Material to Treat the Dry Eye Sydrome

Hyaluronic acid (HA) is a naturally occurring polysaccharide with many molecular functions, including maintaining the structure and physiology of the tissues, tissue remodeling, and inflammation. HA is found naturally in physiological tear fluid, possesses excellent mucus-layer-adhesive properties, and is successfully employed in the treatment of dry eye syndrome (DES). However, HA has as major drawback: its rapid in vivo degradation by hyaluronidase. We report on a unique material, namely, HA-3, obtained by the functionalization of HA with the metalloproteinase inhibitor 3 (MMPI). This material is characterized by an increased resistance to hyaluronidase degradation, associated with MMP inhibition properties. The ability of HA-3 to prevent dehydration of human corneal epithelial cells in vitro and in vivo may accelerate the development of more efficient DES treatment and broaden the application of HA in human diseases

Exploiting the bile acid binding protein as transporter of a Cholic Acid/Mirin bioconjugate for potential applications in liver cancer therapy

Bioconjugation is one of the most promising strategies to improve drug delivery, especially in cancer therapy. Biomolecules such as bile acids (BAs) have been intensively explored as carriers, due to their peculiar physicochemical properties and biocompatibility. BAs trafficking is regulated by intracellular lipid-binding proteins and their transport in the liver can be studied using chicken liver Bile Acid-Binding Proteins (cL-BABPs) as a reference model. Therefore, we conceived the idea of developing a BA-conjugate with Mirin, an exonuclease inhibitor of Mre11 endowed with different anticancer activities, to direct its transport to the liver. Following computational analysis of various BAs in complex with cL-BABP, we identified cholic acid (CA) as the most promising candidate as carrier, leading to the synthesis of a novel bioconjugate named CA-M11. As predicted by computational data and confirmed by X-ray crystallographic studies, CA-M11 was able to accommodate into the binding pocket of BABP. Hence, it can enter BAs trafficking in the hepatic compartment and here release Mirin. The effect of CA-M11, evaluated in combination with varying concentrations of Doxorubicin on HepG2 cell line, demonstrated a significant increase in cell mortality compared to the use of the cytotoxic drug or Mirin alone, thus highlighting chemo-sensitizing properties. The promising results regarding plasma stability for CA-M11 validate its potential as a valuable agent or adjuvant for hepatic cancer therapy

Chemical characterization and antioxidant properties of products and by‐products from Olea europaea L.

The products and by-products of Olea europaea L.: olive fruits (primary agricultural product), oils (primary agro-industrial product), pomaces (agro-industrial processing by-product), and leaves (agricultural practices by-product), are promising sources of bioactive compounds. In the present study, qualitative and quantitative analyses of selected bioactive components in olive fruits, oils, and pomaces were performed. Total polyphenol content and antioxidant activity were analyzed in all samples (humid pomaces 2015: TPP, 26.0 ± 1.5–43.7 ± 3.0 g(GAEq)/kg DW; TEAC/ABTS, 189.5 ± 3.7–388.1 ± 12.0 mmol(Trx)kg DW). Radical (DPPH) quenching potential was analyzed via photometric and EPR methods, obtaining Vis/EPR signal ratio by 1.05 ± 0.45 and 1.66 ± 0.39 for fruits and pomaces, respectively. Through HPLC-UV and HPLC-MS/MS techniques, oleuropein and hydroxytyrosol, as well as selected hydroxycinnamic acids and flavonoids, were identified and quantified in olive fruits and pomaces. The main components were rutin, luteolin, and chlorogenic acid. Cytotoxic assay on fibroblast cells revealed toxic effects for selected extracts at highest tested concentrations (5%)

Click-Chemistry Cross-Linking of Hyaluronan Graft Copolymers

An easy and viable crosslinking procedure by click-chemistry (click-crosslinking) of hyaluronic acid (HA) was developed. In particular, the clickable propargyl groups of hyaluronane-based HA-FA-Pg graft copolymers showing low and medium molecular weight values were exploited in crosslinking by click-chemistry by using a hexa(ethylene glycol) spacer. The resulting HA-FA-HEG-CL materials showed an apparent lack of in vitro cytotoxic effects, tuneable water affinity, and rheological properties according to the crosslinking degree that suggests their applicability in different biomedical fields

Exploring the Antioxidant and Anti-Inflammatory Potential of Saffron (Crocus sativus) Tepals Extract within the Circular Bioeconomy

Repurposing saffron (Crocus sativus) waste presents a sustainable strategy for generating high-value products within the bioeconomy framework. Typically, flower components are discarded after stigma harvest, resulting in significant waste—350 kg of tepals per kilogram of stigmas. This research employed a comprehensive approach, integrating bioactivity studies (in vitro and in silico) with Life Cycle Assessment (LCA) evaluations, to extract and assess bioactive compounds from C. sativus tepals sourced in Tuscany, Italy. Phytochemical characterization using UPLC-MS/MS revealed a high abundance and variety of flavonoids in the hydro-ethanolic extract (CST). The antioxidant capacity was validated through various assays, and the ability to mitigate H2O2-induced oxidative stress and enhance fermentation was demonstrated in Saccharomyces cerevisiae. This study reports that C. sativus tepals extract reduces oxidative stress and boosts ethanol fermentation in yeast, paving the way for applications in the food and biofuels sectors. Further validation in RAW 264.7 macrophages confirmed CST’s significant anti-inflammatory effects, indicating its potential for pharmaceutical, cosmeceutical, and nutraceutical applications. In silico studies identified potential targets involved in antioxidant and anti-inflammatory processes, shedding light on possible interaction mechanisms with Kaempferol 3-O-sophoroside (KOS-3), the predominant compound in the extract. The integration of LCA studies highlighted the environmental benefits of this approach. Overall, this research underscores the value of using waste-derived extracts through “green” methodologies, offering a model that may provide significant advantages for further evaluations compared to traditional methodologies and supporting the circular bioeconomy

Selective fatty acid amide hydrolase inhibitors as potential novel antiepileptic agents

Temporal lobe epilepsy is the most common form of epilepsy, and current antiepileptic drugs are ineffective in many patients. The endocannabinoid system has been associated with an on-demand protective response to seizures. Blocking endocannabinoid catabolism would elicit antiepileptic effects, devoid of psychotropic effects. We herein report the discovery of selective anandamide catabolic enzyme fatty acid amide hydrolase (FAAH) inhibitors with promising antiepileptic efficacy, starting from a further investigation of our prototypical inhibitor 2a. When tested in two rodent models of epilepsy, 2a reduced the severity of the pilocarpine-induced status epilepticus and the elongation of the hippocampal maximal dentate activation. Notably, 2a did not affect hippocampal dentate gyrus long-term synaptic plasticity. These data prompted our further endeavor aiming at discovering new antiepileptic agents, developing a new set of FAAH inhibitors (3a–m). Biological studies highlighted 3h and 3m as the best performing analogues to be further investigated. In cell-based studies, using a neuroblastoma cell line, 3h and 3m could reduce the oxinflammation state by decreasing DNA-binding activity of NF-kB p65, devoid of cytotoxic effect. Unwanted cardiac effects were excluded for 3h (Langendorff perfused rat heart). Finally, the new analogue 3h reduced the severity of the pilocarpine-induced status epilepticus as observed for 2a

Potential use of plants and their extracts in the treatment of coagulation disorders in COVID-19 disease: a narrative review

Abstract: Coronavirus disease, i.e., COVID-19, is caused by the virus called “severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)”. Infection induces predominantly respiratory illness but is also associated with coagulation disorders which play an important role in the pathogenesis, clinical manifestations, and outcome of the disease. The treatment of hemostasis disorders of COVID-19 patients is a difficult problem to solve. For example, heparin is quite effective drug in reducing mortality in severe COVID-19 forms but not able to prevent venous and arterial thromboembolic complications. Moreover, anticoagulant therapy with heparin is associated with several adverse reactions, such as thrombocytopenia, osteoporosis, hypoaldosteronism and hypersensitivity reactions. New alternative anticoagulant molecules can be obtained from plants which are rich in polyphenols and flavonoids. These compounds, besides being potent antioxidants, also possess anti-inflammatory effect and, because able to inhibit the activity of many enzymes, including serine proteases, also anticoagulant properties. The purpose of this narrative review is to provide an overview of current literature data on coagulation disorders associated with COVID-19 disease and of the anticoagulant activity of plants and their extracts in order to evaluate their possible clinical application as alternative sources of novel molecules with anticoagulant and antithrombotic activity for the treatment of coagulation disorders in patients with COVID-19

Preliminary In Vitro Cytotoxicity, Mutagenicity and Antitumoral Activity Evaluation of Graphene Flake and Aqueous Graphene Paste

1nononeThis study aimed to determine the in vitro cytotoxicity and mutagenicity of graphene flake (GF) and aqueous graphene paste (AGP) in order to evaluate their potential for application as biomaterials. Furthermore, their antitumor activity against adherent and suspended cells, namely, human breast adenocarcinoma cells (MDA‐MB‐231), and human monocytes from histiocytic lymphoma (U‐937), was investigated. The results demonstrated that GF reduced the viability and proliferation of NIH3T3 immortalized murine fibroblasts for concentrations >0.8 μg/mL and incubation times of 48 and 72 h. AGP showed no toxic effects in any of the tested concentrations and incubation times. The same results were obtained for MDA‐MB‐231 cells. The viability of the U‐937 cells was not affected by either GF or AGP. The Ames test showed that GF and AGP were not genotoxic against Salmonella typhimurium strains TA98 and TA100, with and without metabolic activation. The present study demonstrated good in vitro cellular compatibility of GF and AGP and. Among these, AGP was the best material as it did not interfere, at any of the tested concentrations, with cell viability and proliferation for up to 72 h of incubation. In any case, neither material induced alterations to cell morphology and were not mutagenic.restrictedLamponi S.Lamponi, S