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Neurodegenerative diseases represent a growing global health burden. With current treatments limited to symptom management, natural biodiversity offers a promising source of novel, multi-target compounds. Bioprospecting thus emerges as a sustainable strategy for discovering innovative neuroprotective therapies, underscoring the importance of preventing biodiversity for future drug discovery. An initial metabolomic screening of Italian plants was performed to support a bioprospective approach, in which 27 plant extracts were evaluated for their ability to inhibit acetylcholinesterase and tyrosinase, targeting mechanisms involved in neurodegenerative diseases. Adenophora liliifolia and Carissa macrocarpa emerged as the most promising species through multi-parameter screening. Metabolomic analysis showed that most identified metabolites exhibit activity against acetylcholinesterase and/or tyrosinase, supporting observed bioactivities. These extracts represent potential candidates for developing therapies against neurodegenerative diseases. These findings highlight systematic bioprospecting as a powerful strategy for identifying novel candidates with neuroprotective activity. By integrating traditional knowledge with modern metabolomic and biochemical approaches, this study demonstrates how underexplored plant biodiversity, such as Adenophora liliifolia and Carissa macrocarpa , can yield promising therapeutic candidates for targeting the complex multi-target mechanisms underlying neurodegenerative disorders.

Apricot kernels (Prunus armeniaca L.) represent a valuable by-product of stone fruit cultivation, offering diverse applications in food, cosmetic, and pharmaceutical industries. While apricot kernel oil is recognized for its rich composition of unsaturated fatty acids, phenolics, and tocopherols, its therapeutic potential, particularly in cancer prevention, remains unexplored. This study investigated a purified fraction (FOPF) obtained from Farclo variety kernel oil, cultivated in the Emilia-Romagna region of Italy and selected for its naturally low amygdalin content. In vitro studies demonstrated FOPF’s significant antiproliferative effects against colorectal cancer (LoVo, HT29) and hepatocarcinoma (Hep3B) cell lines, with GI50 values ranging from 0.06 to 0.09 mg/mL. The fraction induced cell cycle arrest and significantly inhibited cancer cell migration, effects mediated through PPAR-γ expression modulation. These findings establish FOPF’s potential as a natural chemopreventive agent and provide a foundation for its development as a nutraceutical ingredient targeting colorectal and hepatic cancers.

During the years, many usnic acid (UA) conjugates have been synthesized to obtain potent endowed with biological properties. Since (S)-UA is less abundant in nature than (R)-enantiomer, it is difficult to source, thus precluding a deeper investigation. Among the lichens producing UA, Cladonia foliacea is a valuable (S)-UA source. In the present work, we report on a rapid HPLC-UV/PAD-CD protocol suitable for the analysis and the identification of the main secondary metabolites present in C. foliacea extract. Best results were achieved using XBridge Phenyl column and acetonitrile and water, which were both added with formic acid as mobile phase in gradient elution. By combining analytical, spectroscopical, and chiroptical analysis, the most abundant analyte was unambiguously identified as (S)-UA. Accordingly, a versatile microwave-assisted extractive (MAE) protocol, assisted by a design of experiment (DoE), to quantitatively recover (S)-UA was set up. The best result in terms of UA extraction yield was obtained using ethanol and heating at 80 °C under microwave irradiation for 5 min. Starting from 100 g of dried C. foliacea, 420 mg of (S)-UA were achieved. Thus, our extraction method resulted in a suitable protocol to produce (S)-UA from C. foliacea for biological and pharmaceutical investigation or commercial purposes.

Premise Leaf extracts are valuable sources of bioactive compounds. However, co‐extracted chlorophylls interfere with analyses, including spectroscopic and biochemical assays. Existing methods for chlorophyll removal often have limitations, including the use of hazardous solvents, low specificity, or high costs. Methods and Results A solid‐phase extraction protocol for chlorophyll removal from leaf extracts of Corylus avellana was developed using commercially available cartridges. The method requires standard equipment, can be completed within 10 minutes, and is scalable from analytical to preparative quantities. We validated this protocol across 20 taxa, demonstrating the removal of 85% of chlorophylls, successful scale up of quantities, cartridge reusability, and low solvent consumption. Conclusions Key innovations of the protocol include simplified elution steps and the possibility of multiple reuse cycles. The simplicity, sustainability, and scalability of this new protocol make it particularly valuable for high‐throughput applications and process development.

The aim of the present work was to load a Hibiscus sabdariffa (HS) hydroalcoholic extract into in situ gelling formulations for the treatment of oral mucositis and esophagitis. Such formulations, selected as the most promising options in a previous work of ours, were composed by κ-carrageenan (κ-CG), a sulfated marine polymer able to gelify in presence of saliva ions, hydroxypropyl cellulose (HPC), used as mucoadhesive agent, and CaCl2, salt able to enhance the interaction κ-CG/saliva ions. HS extract, which is rich in phytochemicals such as polyphenols, polysaccharides and organic acids, was selected due to its antioxidant and anti-inflammatory properties. For HS extraction, three different methodologies (maceration, Ultrasound Assisted Extraction (UAE) and Microwave Assisted Extraction (MAE)) were compared in terms of extraction yield and extract antioxidant activity, revealing that MAE was the best procedure. Rheological and mucoadhesive properties of HS-loaded formulations were investigated. Such formulations were characterized by a low viscosity at 25 °C, guaranteeing an easy administration, a proper in situ gelation behavior and marked elastic and mucoadhesive properties at 37 °C, functional to a protective action towards the damaged mucosa. Finally, the biocompatibility and the proliferative effect of HS-loaded formulations, as well as their antioxidant and anti-inflammatory properties, were proved in vitro on human dermal fibroblasts.

Life expectancy in high-income countries is increasing, leading to a higher incidence of age-related neurodegenerative diseases. To address this urgent medical need, several molecular targets have been identified, including advanced glycation end products (AGEs) and tyrosinase. Given the well-established role of diet in counteracting degenerative processes, this study aimed to identify a potential food ingredient with combined anti-tyrosinase and anti-glycative properties. L. was selected based on its inclusion in the BelFrIt list and its known content of tyrosinase inhibitors, such as benzoxazinones and verbascoside. Extraction of leaves was optimized using a design of experiments approach, comparing microwave- and ultrasound-assisted techniques. Optimal conditions were achieved using microwave-assisted extraction with ethanol 80%, 80 °C, one cycle, drug-to-solvent ratio of 10 mL/g. The optimized extract (at 5 mg/mL) inhibited tyrosinase activity by approximately 47%, increasing to 58% after chlorophyll removal. Moreover, the extract reduces AGEs formation in presence of methylglyoxal, with an activity at 1 mg/mL comparable with that of a well-known anti-glycative agent. A similar trend was observed in the reduction in methylglyoxal and glyoxal levels. Overall, these results support the potential of the optimized extract as a functional food ingredient to counteract aging-related neurodegeneration.

Olive cultivation generates substantial pruning waste, yet current valorization strategies focus solely on leaves despite the logistical challenges of separating them. This study optimized the extraction of bioactive compounds from unseparated pruning waste (branches and leaves) using a D-optimal design of experiments to evaluate solvent composition, temperature, and time effects in thirteen experiments. Optimized conditions were scaled up, and extracts were tested via DPPH, ORAC assays, and ROS inhibition in HaCaT cells. Extracts from unseparated pruning waste demonstrated antioxidant capacity equivalent to isolated leaf extracts, and effectiveness in reducing the oxidative stress by approximately 60% compared to the H2O2 condition. This approach eliminates costly leaf separation while maintaining bioactivity, offering a scalable circular economy solution for olive waste management. The practical implications are substantial: whole pruning waste valorization reduces processing costs and time, decreases agricultural waste by utilizing currently discarded branches, and simplifies supply chains for industries requiring olive-derived antioxidants. Our findings challenge the current paradigm in olive waste biorefining, providing a more economically viable and environmentally sustainable pathway for producing antioxidant-rich extracts suitable for cosmetics, nutraceutical, and pharmaceutical applications.

Multiple Myeloma (MM) is an aggressive tumor causing millions of deaths every year and currently available therapies are often unsuccessful or correlated with severe side effects. In our previous work we demonstrated that the Hibiscus sabdariffa hydroalcoholic extract inhibits the growth of the MM cell line and we isolated two metabolites responsible for the activity: Hib-ester and Hib-carbaldehyde. Herein we report their interaction with proteasome, one of the main targets in the fight against MM. The molecular modelling study outlined a good interaction of both compounds with the target and these results prompted us to investigate their potential to inhibit proteasome. Metabolites were then isolated from the calyces and an extract with a high content of Hib-ester and Hib-carbaldehyde was prepared. An anticancer profile was drawn, evaluating apoptosis, autophagy and proteasome inhibition, with the anticancer properties being mainly attributed to the Hib-ester and Hib-carbaldehyde, while the proteasome inhibition of the extract could also be ascribed to the presence of anthocyanins, a class of secondary metabolites already known for their proteasome inhibitory activity.

LsrK is a bacterial kinase that triggers the quorum sensing, and it represents a druggable target for the identification of new agents for fighting antimicrobial resistance. Herein, we exploited tryptophan fluorescence spectroscopy (TFS) as a suitable technique for the identification of potential LsrK ligands from an in-house library of chemicals comprising synthetic compounds as well as secondary metabolites. Three secondary metabolites (Hib-ester, Hib-carbaldehyde and (R)-ASME) showed effective binding to LsrK, with KD values in the sub-micromolar range. The conformational changes were confirmed via circular dichroism and molecular docking results further validated the findings and displayed the specific mode of interaction. The activity of the identified compounds on the biofilm formation by some Staphylococcus spp. was investigated. Hib-carbaldehyde and (R)-ASME were able to reduce the production of biofilm, with (R)-ASME resulting in the most effective compound with an EC50 of 14 mg/well. The successful application of TFS highlights its usefulness in searching for promising LsrK inhibitor candidates with inhibitor efficacy against biofilm formation.

Multiple myeloma (MM) belongs to hematological cancers and its incidence is increasing worldwide. Despite recent advances in its therapy, MM still causes many deaths every year. In fact, current therapies sometimes fail and are associated with severe adverse effects, including neurotoxicity. As a part of our ongoing efforts to discover new potential therapies against MM, we prepared Hibiscus sabdariffa extracts obtained by a microwave-assisted solvent extraction and investigate their activity by in vitro assays on the RPMI-8226 cell line. The bioguided fractionation of the crude ethanolic extract allowed the identification of HsFC as the most effective extract. We assessed cell viability (MTT and Tripan blue test), cell migration (Boyden chamber assay), and neurotoxicity (DRG neurotoxicity assay). The promising results prompted us to further fractionate HsFC and we obtained two molecules effective against RPMI-8226 cells without neurotoxic effects at their active concentrations. Moreover, both compounds are able to significantly reduce cell migration.