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Background/Objectives: Urinary tract infections (UTIs) are infections that involve the urethra, bladder, and, in much more severe cases, even kidneys. These infections represent one of the most common diseases worldwide. Various pathogens are responsible for this condition, the most common being Escherichia coli (E. coli). Bromelain is a proteolytic complex obtained from the stem and stalk of Ananas comosus (L.) Merr. showing several beneficial activities. In addition to bromelain, N-acetylcysteine (NAC) has also been used. Methods: The purpose of this experiment was to evaluate the antibacterial, anti-motility, and anti-biofilm effects of a new polyenzymatic complex (DIF17BRO®) in combination with NAC (the Formulation) on various strains of E. coli isolated from patients with UTIs. Subsequently, the anti-inflammatory and antioxidant effects of the Formulation were studied in an ex vivo model of cystitis, using bladder samples from mice exposed to E. coli lipopolysaccharide (LPS). Results: Our results showed that the Formulation significantly affects the capability of bacteria to form biofilm and reduces the bacteria amount in the mature biofilm. Moreover, it combines the interesting properties of NAC and a polyenzyme plant complex based on bromelain in a right dose to affect the E. coli adhesion capability. Finally, the Formulation exhibited protective effects, as confirmed by the inhibitory activities on multiple inflammatory and oxidative stress-related pathways on bladder specimens exposed to LPS. Conclusions: This blend of active compounds could represent a promising and versatile approach to use to overcome the limitations associated with conventional therapies.

Chronic inflammation is a recognized risk factor for various cancers, including prostate cancer (PCa). We aim to explore the potential protective effects of aged black garlic extract (ABGE) against inflammation-induced prostate damage and its impact on prostate cancer cell lines. We used an ex vivo model of inflammation induced by Escherichia coli lipopolysaccharide (LPS) on C57BL/6 male mouse prostate specimens to investigate the anti-inflammatory properties of ABGE. The gene expression levels of pro-inflammatory biomarkers (COX-2, NF-κB, and TNF-α, IL-6) were measured. Additionally, we evaluated ABGE’s therapeutic effects on the prostate cancer cell lines through in vitro functional assays, including colony formation, tumorsphere formation, migration assays, and phosphorylation arrays to assess the signaling pathways (MAPK, AKT, JAK/STAT, and TGF-β). ABGE demonstrated significant anti-inflammatory and antioxidant effects in preclinical models, partly attributed to its polyphenolic content, notably catechin and gallic acid. In the ex vivo model, ABGE reduced the gene expression levels of COX-2, NF-κB, TNF-α, and IL-6. The in vitro studies showed that ABGE inhibited cell proliferation, colony and tumorsphere formation, and cell migration in the prostate cancer cells, suggesting its potential as a therapeutic agent. ABGE exhibits promising anti-inflammatory and anti-cancer properties, supporting further investigation into ABGE as a potential agent for managing inflammation and prostate cancer.

The enormous burden of the COVID-19 pandemic in economic and healthcare terms has cast a shadow on the serious threat of antimicrobial resistance, increasing the inappropriate use of antibiotics and shifting the focus of drug discovery programmes from antibacterial and antifungal fields. Thus, there is a pressing need for new antimicrobials involving innovative modes of action (MoAs) to avoid cross-resistance rise. Thiosemicarbazones (TSCs) stand out due to their easy preparation and polypharmacological application, also in infectious diseases. Recently, we reported a small library of TSCs (1–9) that emerged for their non-cytotoxic behaviour. Inspired by their multifaceted activity, we investigated the antibacterial, antifungal, and antidermatophytal profiles of derivatives 1–9, highlighting a new promising research line. Furthermore, the ability of these compounds to inhibit selected microbial and human carbonic anhydrases (CAs) was assessed, revealing their possible involvement in the MoA and a good selectivity index for some derivatives.

The present study was designed to determine the phenolic constituents, antioxidant, and enzyme inhibition activities of aerial parts and bulbs of Allium lycaonicum (family Amaryllidaceae). Extracts were prepared by maceration and Soxhlet/infusion using hexane, methanol, and water as extraction solvents. Generally, extracts from the aerial parts showed higher total phenolic and individual components and antioxidant activity than their respective bulb extracts. Maceration with water was the best to extract total phenolic content from the aerial parts (29.00 mg gallic acid equivalents (GAE)/g), while the Soxhlet extraction with hexane (22.29 mg GAE/g) was the best for the bulb. Maceration with methanol recovered the highest total flavonoid content from both the aerial parts (41.95 mg (rutin equivalents (RE)/g) and bulb (1.83 mg RE/g). Polar extracts of aerial parts were characterized by higher abundance of kaempferol-3-glucoside (≤20,624.27 µg/mg), hyperoside (≤19,722.76 µg/g), isoquercitrin (≤17,270.70 µg/g), delphindin-3,5-diglucoside (≤14,625.21 µg/g), and rutin (≤10,901.61 µg/g) than the bulb. Aerial parts’ aqueous extract, prepared by maceration, exerted the highest anti-ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical activity (64.09 mg trolox equivalents (TE)/g), Cu++ (83.03 mg TE/g) and Fe+++ (63.03 mg TE/g) reducing capacity while that prepared by infusion recorded the highest anti-DPPH (2,2-diphenyl-1-picrylhydrazyl) radical (31.70 mg TE/g) and metal chelating (27.66 mg EDTAE/g) activities. The highest total antioxidant activity (1.46 mmol TE/g) was obtained by maceration of the bulb with water. Extracts obtained by organic solvents showed remarkable enzyme inhibition properties against the tested enzymes. Soxhlet extraction of the bulb with hexane and methanol recorded the highest acetylcholinesterase inhibition (4.75 mg galanthamine equivalents (GALAE)/g) and tyrosinase inhibition (139.95 mg kojic acid equivalents/g) activities, respectively. Extracts obtained by maceration of the bulb with methanol and the aerial parts with hexane exerted the highest glucosidase inhibition (3.25 mmol acarbose equivalents/g) and butyrylcholinesterase inhibition (20.99 mg GALAE/g) activities, respectively. These data indicated that A. lycaonicum is a source of bioactive molecules with potential antioxidant and enzyme inhibition properties. Nonetheless, the extracts obtained through various solvents and extraction techniques showed variations in their phytoconstituent composition and biological properties.

In the present study, we performed comprehensive LC-MS chemical profiling and biological tests of Vepris boiviniana leaves and stem bark extracts of different polarities. In total, 60 bioactive compounds were tentatively identified in all extracts. The 80% ethanolic stem bark extract exhibited the highest activity in the ABTS assay, equal to 551.82 mg TE/g. The infusion extract of stem bark consistently demonstrated elevated antioxidant activity in all assays, with values ranging from 137.39 mg TE/g to 218.46 mg TE/g. Regarding the enzyme inhibitory assay, aqueous extracts from both bark and leaves exhibited substantial inhibition of AChE, with EC50 values of 2.41 mg GALAE/g and 2.25 mg GALAE/g, respectively. The 80% ethanolic leaf extract exhibited the lowest cytotoxicity in VERO cells (CC50: 613.27 µg/mL) and demonstrated selective cytotoxicity against cancer cells, particularly against H1HeLa cells, indicating potential therapeutic specificity. The 80% ethanolic bark extract exhibited elevated toxicity in VERO cells but had reduced anticancer selectivity. The n-hexane extracts, notably the leaves’ n-hexane extract, displayed the highest toxicity towards non-cancerous cells with selectivity towards H1HeLa and RKO cells. In viral load assessment, all extracts reduced HHV-1 load by 0.14–0.54 log and HRV-14 viral load by 0.13–0.72 log, indicating limited antiviral activity. In conclusion, our research underscores the diverse bioactive properties of Vepris boiviniana extracts, exhibiting potent antioxidant, enzyme inhibitory, and cytotoxicity potential against cancer cells.

The beech mushroom (Hypsizygus marmoreus) is a highly nutritious, edible medicinal mushroom native to East Asia. The present research investigated the impact of different substrates on the metabolite compositions of H. marmoreus mycelia cultivated in vitro. The substrates tested included malt extract agar, malt extract agar enriched with barley malt, and malt extract agar enriched with grape pomace. The study also assessed antimicrobial and antiradical activities of the extracts against gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus), gram-negative bacteria (Escherichia coli, Salmonella typhi, and Pseudomonas aeruginosa), yeasts (Candida albicans, C. tropicalis, and C. parapsilosis), and dermatophytes (Trichophyton mentagrophytes, T. tonsurans, T. rubrum, Arthroderma quadrifidum, A. gypseum, A. curreyi, and A. insingulare). The results revealed that the H. marmoreus mycelia extracts demonstrated antibacterial and antifungal activities against the tested microorganisms. Extracts obtained from the cultivation in substrates enriched with either barley malt or grape pomace exhibited the highest antibacterial activity among all the tested bacterial strains except for P. aeruginosa. The same extracts showed the highest inhibitory effect against C. albicans and C. parapsilosis. Noteworthy, the extract from the mushroom cultivated in the substrate enriched with grape pomace also exhibited remarkable efficacy against T. mentagrophytes and T. tonsurans. Terpenoid and carbapenem compounds could be related to the antimicrobial properties of the extracts from mushrooms cultivated in substrates enriched with grape pomace. In comparison, the higher antiradical properties could be related to the content of indole compounds. In conclusion, growth substrate selection affects the nutritional and medicinal properties of H. marmoreus, making it a valuable contribution to the understanding of the cultivation of this mushroom.

Plants from the Nepeta genus have been proved to possess different pharmacological properties, among which are antimicrobial, antioxidant, anti-inflammatory, analgesic, and cytotoxic effects. Nepeta italica is a medicinal plant traditionally used for its analgesic effects, and in the present study, the phytochemical composition and biological effects of hexane, dichloromethane (DCM), ethyl acetate (EA), ethanol, ethanol-water, and water extracts of the aerial parts were investigated for determining phenolic composition, antioxidant effects, and anti-inflammatory effects in isolated mouse colon specimens exposed to lipopolysaccharide (LPS). Polar extracts were the richest in terms of phenolic compounds, especially rosmarinic acid. In parallel, ethanol, ethanol-water, and water extracts were also the most effective as scavenging/reducing and enzyme inhibition agents, especially towards cholinesterases and α-glucosidase, and in inhibiting the LPS-induced cyclooxygenase-2 (COX-2) and tumor necrosis factor α (TNFα) gene expression in mouse colon. This poses the basis for future in vivo investigations for confirming the protective effects of polar extracts of N. italica against inflammatory bowel diseases.

Fomitopsis officinalis is a holartic polyporous mushroom that forms large fruiting bodies on old standing trees, fallen logs, or stumps. F. officinalis is a medicinal mushroom species that is most commonly used in traditional European medicine. In this study, we explore the spatial metabolic differences in F. officinalis’ mushroom parts, i.e., the cap (median and apical parts) and the hymenium. Additionally, chromatographic analysis was conducted in order to unravel the composition of specialized metabolites in the hydroalcoholic mushroom extracts. The potential antifungal and bacterial effects of extracts were tested against pathogen strains of Gram+ and Gram– bacteria, and yeast, dermatophytic, and fungal-pool species. Extracts from the apical part were the richest in terms of phenolic compounds; consistent with this finding, the extracts were also the most effective antiradical and antimicrobial agents with MIC values < 100 µg/mL for most of the tested bacterial and dermatophytic species. According to these findings, F. officinalis extracts are valuable sources of primary and secondary metabolites, thus suggesting potential applications in the formulation of food supplements with biological properties in terms of antioxidant and antimicrobial activities.

Multiple studies demonstrated biological activities of aged black garlic, including anti-inflammatory, antioxidant, and cardioprotective effects. We aimed to investigate the protective effects of an aged black garlic water extract (ABGE) alone or in association with multivitamins consisting of combined Vitamins D, C, and B12, on mouse heart specimens exposed to E. coli lipopolysaccharide (LPS). Moreover, we studied the hydrogen sulphide (H2S) releasing properties and the membrane hyperpolarization effect of the Formulation composed by ABGE and multivitamins, using Human Aortic Smooth Muscle Cells (HASMCs). ABGE, vitamins D and C, and the Formulation suppressed LPS-induced gene expression of cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, interleukin (IL)-6, nuclear factor-kB (NF-kB), and inducible nitric oxide synthase (iNOS) on mouse heart specimens. The beneficial effects induced by the extract could be related to the pattern of polyphenolic composition, with particular regard to gallic acid and catechin. The Formulation also increased fluorescence values compared to the vehicle, and it caused a significant membrane hyperpolarization of HASMCs compared to ABGE. To conclude, our present findings showed that ABGE, alone and in association with multivitamins, exhibited protective effects on mouse heart. Moreover, the Formulation increased intracellular H2S formation, further suggesting its potential use on cardiovascular disease.

Pelargonium quercetorum is a medicinal plant traditionally used for treating intestinal worms. In the present study, the chemical composition and bio-pharmacological properties of P. quercetorum extracts were investigated. Enzyme inhibition and scavenging/reducing properties of water, methanol, and ethyl acetate extracts were assayed. The extracts were also studied in an ex vivo experimental model of colon inflammation, and in this context the gene expression of cyclooxygenase-2 (COX-2) and tumor necrosis factor α (TNFα) were assayed. Additionally, in colon cancer HCT116 cells, the gene expression of transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8), possibly involved in colon carcinogenesis, was conducted as well. The extracts showed a different qualitative and quantitative content of phytochemicals, with water and methanol extracts being richer in total phenols and flavonoids, among which are flavonol glycosides and hydroxycinnamic acids. This could explain, at least in part, the higher antioxidant effects shown by methanol and water extracts, compared with ethyl acetate extract. By contrast, the ethyl acetate was more effective as cytotoxic agent against colon cancer cells, and this could be related, albeit partially, to the content of thymol and to its putative ability to downregulate TRPM8 gene expression. Additionally, the ethyl acetate extract was effective in inhibiting the gene expression of COX-2 and TNFα in isolated colon tissue exposed to LPS. Overall, the present results support future studies for investigating protective effects against gut inflammatory diseases.

Sour cherries fruits (Prunus cerasus L., syn P. cerasus var. austera) are locally known as “visciola di Sezze”, due to the name of the city where they are traditionally cultivated in Lazio Region, Italy. Fruit samples from three harvesting years (June 2019, 2020 and 2021), were submitted to a protocol of analyses to detect the bioactive content based on year of harvest, freezing, homogenization and thermic treatments. Polyphenolic components, particularly anthocyanin compounds, were extracted, purified and analyzed by HPLC-DAD and DI-ESI-MS. An anthocyanin content between 0.24 and 21 mg/g fresh weight and a flavonols content between 0.04 and 0.2 mg/g fresh weight were found, depending on the harvest year and the applied procedures. Anthocyanins, besides being the principal components, were mainly represented by cyanidin-3-glucosyl-rutinoside (about 80%), a not particularly widespread molecule, mostly accounting for polyphenolic content. Color analysis and anti-radical activity of the different obtained extracts were performed with the aim to correlate organoleptic characters and health potential to the detected anthocyanins and flavanols content. Results show that immediate post-harvest freezing is the best way to preserve the bioactive content, the correlated color expression and anti-radical activity.

Cannabis sativa products have historically been used for healing purposes; now their biological properties are supported with scientific evidence, but modern research has not yet fully developed its therapeutic potential. This study focuses on the cultivar of C. sativa called strawberry to understand the biological and medical potentials of hydroalcoholic extracts from two different parts of the plant: leaves and inflorescences. Two biological assets were investigated including antioxidant and antimicrobial potential. Additionally, quantitative determination of phenolic and terpenophenol compounds was conducted. The antimicrobial action was highlighted for the hydroalcoholic extract from inflorescences, especially against Escherichia coli and Bacillus subtilis. Among the dermatophytes’ strains, the most sensitive was Arthroderma currey. These effects could be related albeit partially to the pattern of the phenolics detected, among which the most prominent one was benzoic acid. On the other hand, antioxidant and antimicrobial effects of the extracts could be also mediated by the main terpenophenolics identified and quantified, namely cannabidiolic acid and cannabidiol. Collectively, the present data point to the potential use of the inflorescences from the C. sativa cultivar strawberry as a valuable plant material for the development of bioactive extracts with antioxidant and antimicrobial effects

In this study, the methanolic and infusion extracts of two species, Thymbra capitata and Thymus sipyleus subsp. rosulans, were tested for their chemical composition and biological abilities (antioxidant, enzyme inhibitory and anti-inflammatory effects). The extracts yielded total phenolic and flavonoid contents in the range of 83.43–127.52 mg GAE/g and 9.41–46.34 mg RE/g, respectively. HPLC analysis revealed rosmarinic acid to be a major component of the studied extracts (15.85–26.43%). The best ABTS radical scavenging ability was observed in the methanol extract of T. capitata with 379.11 mg TE/g, followed by in the methanol extract of T. sipylus (360.93 mg TE/g). In the CUPRAC assay, the highest reducing ability was also found in the methanol extract of T. capitata with 802.22 mg TE/g. The phosphomolybdenum ability ranged from 2.39 to 3.61 mmol TE/g. In terms of tyrosinase inhibitory effects, the tested methanol extracts (83.18–89.66 mg KAE/g) were higher than the tested water extracts (18.74–19.11 mg KAE/g). Regarding the BChE inhibitory effects, the methanol extracts were active on the enzyme while the water extracts showed no inhibitory effect on it. Overall, the methanolic extracts showed better enzyme inhibition compared to the infusion extracts. Molecular docking also showed the selected exhibited potential binding affinities with all enzymes, with a preference for cholinesterases. Additionally, the extracts were effective in attenuating the LPS-induced increase in COX-2 and IL-6 gene expression in isolated colon, thus indicating promising anti-inflammatory effects. The preliminary results of this study suggest that these species are good natural sources of antioxidants and also provide some scope as enzyme inhibitors, most likely due to their bioactive contents such as phenolic acids, and thus can be exploited for different applications related to health promotion and disease prevention.

Inflammatory bowel diseases (IBDs) are chronic and multifactorial inflammatory conditions of the colonic mucosa (ulcerative colitis), characterized by increased and unbalanced immune response to external stimuli. Garlic and its bioactive constituents were reported to exert various biological effects, including anti-inflammatory, antioxidant and immunomodulatory activities. We aimed to evaluate the protective effects of a hydroalcoholic (GHE) and a water (GWE) extract from a Sicilian variety of garlic, known as Nubia red garlic, on an ex vivo experimental model of ulcerative colitis, involving isolated LPS-treated mouse colon specimens. Both extracts were able to counteract LPS-induced cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, nuclear factor-kB (NF-kB), and interleukin (IL)-6 gene expression in mouse colon. Moreover, the same extracts inhibited prostaglandin (PG)E2, 8-iso-PGF2α, and increased the 5-hydroxyindoleacetic acid/serotonin ratio following treatment with LPS. In particular, GHE showed a better anti-inflammatory profile. The anti-inflammatory and antioxidant effects induced by both extracts could be related, at least partially, to their polyphenolic composition, with particular regards to catechin. Concluding, our results showed that GHE and GWE exhibited protective effects in colon, thus suggesting their potential use in the prevention and management of ulcerative colitis.

Pleurotus species isolated in vitro were studied to determine the effect of different media on their production of secondary metabolites, antimicrobial, and antioxidant activity. The different metabolites among Pleurotus samples covered a total of 58 pathways. Comparisons were made between the metabolic profiles of Pleurotus spp. mycelia grown in two substrates: Potato-dextrose-agar-PDA, used as control (S1), and PDA enriched with 0.5 % of wheat straw (S2). The main finding was that the metabolic pathways are strongly influenced by the chemical composition of the growth substrate. The antibacterial effects were particularly evident against Escherichia coli, whereas Arthroderma curreyi (CCF 5207) and Trichophyton rubrum (CCF 4933) were the dermatophytes more sensitive to the mushroom extracts. The present study supports more in-depth investigations, aimed at evaluating the influence of growth substrate on Pleurotus spp. antimicrobial and antioxidant properties.

‘Sulmona red garlic’ is an Italian variety characterized by a red tunica surrounding a white bulb. Red tunicae and non-commercial small bulbs are food wastes that must be studied for their added value. Hydroalcoholic extracts, obtained by separated inner and outer tunicae and peeled bulbs of small commercial ‘Sulmona red garlic’ bulbs, harvested at two different years, were first characterized with respect to their color, polyphenolic content, and antiradical activity. Then, an untargeted metabolic profile by means of electrospray ionization Fourier transform ion cyclotron resonance (ESI FT-ICR) mass spectrometry led to a comparative evaluation of the chemical diversity of six different samples. The study was completed by biological tests aiming to evaluate the associated health potential. Data on monocytes/macrophages showed good biocompatibility and a promising cytoprotective effect under oxidative stress conditions of all the extracts. At a molecular level, all the garlic extracts were able to downregulate the hydrogen peroxide-induced cyclooxygenase-2 and inducible nitric oxide synthase expression through the modulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB) and peroxynitrite intracellular amounts, at different extents depending on the extract, the cell type, and the concentration. On the whole, data highlight an associated health potential of the extracts of this waste plant material both in terms of cytoprotection and of anti-inflammatory activity.

Pollen extract represents an innovative approach for the management of the clinical symptoms related to prostatitis and pelvic inflammatory disease (PID). In this context, the aims of the present work were to analyze the phenolic composition of a hydroalcoholic extract of PollenAid Plus soft gel capsules, and to evaluate the extract’s cytotoxic effects, in human prostate cancer PC3 cells and human ovary cancer OVCAR-3 cells. Additionally, protective effects were investigated in isolated prostate and ovary specimens exposed to lipopolysaccharide (LPS). The phytochemical investigation identified catechin, chlorogenic acid, gentisic acid, and 3-hydroxytyrosol as the prominent phenolics. The extract did not exert a relevant cytotoxic effect on PC3 and OVCAR-3 cells. However, the extract showed a dose-dependent inhibition of pro-inflammatory IL-6 and TNF-α gene expression in prostate and ovary specimens, and the extract was effective in preventing the LPS-induced upregulation of CAT and SOD gene expression, which are deeply involved in tissue antioxidant defense systems. Finally, a docking approach suggested the capability of catechin and chlorogenic acid to interact with the TRPV1 receptor, playing a master role in prostate inflammation. Overall, the present findings demonstrated anti-inflammatory and antioxidant effects of this formulation; thus, suggesting its capability in the management of the clinical symptoms related to prostatitis and PID.

Intensive farming systems represent a stressful environment for pigs and negatively influence neuroendocrine functions, behavior, and performance. Outdoor farming is an alternative option, which is thought to imply several beneficial effects for the animal. Dietary essential oils are known to be an innovative strategy to improve pig health and performance, and oregano essential oil (ORE) possesses beneficial effects due to its antimicrobial, anti-fungal, and antioxidant properties. We tested the effect of dietary ORE on peripheral blood mononuclear cells (PBMCs) in 36 growing pigs, either reared under indoor or outdoor conditions. Quantitative real-time PCR (RT-qPCR) assay was used to evaluate the effect of diet (control vs. ORE) and the time of sampling (T1−120 days vs. T2−190 days) on the expression of inflammatory and immune-related genes (TNF, IL1β, IL8, IL18, IL10, IL1RN, STAT3, HSP90, ICAM-1, and NFKB1). Under outdoor condition, the majority of transcripts were upregulated (p < 0.05), assuming a general inflammatory status (TNF, HSP90, NFKB1, IL1β, and STAT3). However, an interaction between diet and the farming system was observed: HSP90, NFKB1, and STAT3 were downregulated (p < 0.05) in the outdoor reared pigs when fed the ORE diet. Our study showed that bioactive compounds of ORE exert their activity, especially when the animals are exposed to stressful stimuli. Dietary ORE can be an acceptable strategy to help pigs tolerate the stress related to the harsh, outdoor, rearing conditions.

MOMAST® GR25 is a polyphenolic granular complex from olive pressing juice with high total content in polyphenols. In this work, we evaluated the possible anti-inflammatory effects of MOMAST® GR25 in both acute and chronic inflammatory models. MOMAST® GR25 decreased the levels of prostaglandin (PG) E2 and 8-iso-PGF2α in isolated rat colon, liver, and heart specimens stimulated with lipopolysaccharide (LPS). In vivo, compared to controls, rats treated with MOMAST® GR25 (100 mg/kg to 1 g/kg) showed a significant reduction in both licking/biting time in the formalin test. In a rat model of osteoarthritis by monoiodoacetate (MIA) injection, MOMAST® GR25 showed pain-relieving properties when acutely administered, reducing mechanical hyperalgesia and spontaneous pain. Moreover, a repeated daily treatment with MOMAST® GR25 (300 mg/kg) fully counteracted osteoarticular pain without the development of tolerance to the antinociceptive effect. Taken together, our present findings showed that MOMAST® GR25 could represent a potential strategy for the treatment of inflammation and pain.

Bacteria belonging to Staphylococcus genus, in particular methicillin-resistant Staphylococcus aureus and multidrug-resistant Staphylococcus epidermidis, together with Cutibacterium acnes are the main strains involved in skin disease. The increase in multidrug-resistant bacteria has revived attention on natural compounds as alternative agents for the treatment management. Among these, hop extract, a hydroalcoholic solution obtained from experimental crops of Humulus lupulus L. variety cascade (hop), displays diverse biological properties including an antimicrobial one. The aim of this study was to evaluate the antimicrobial activity and the capacity to inhibit the biofilm formation of a characterized hop extract against S. aureus and S. epidermidis multidrug-resistant strains and against a C. acnes strain. The hop extract was characterized by (i) phytochemical analysis through a reversed-phase high-performance liquid chromatography (HPLC)–fluorimetric method, (ii) biocompatibility test with Artemia salina L., (iii) cytotoxicity against two cell lines, (iv) docking analysis, and (v) antimicrobial and antibiofilm activities by detection of zones inhibition, minimal inhibitory concentrations (MICs), biomass quantification, and cell viability. The hop extract was biocompatible and non-cytotoxic at all tested concentrations. HPLC analysis revealed significant levels of gallic acid, resveratrol, and rutin. This last compound was the most representative displaying a high affinity against PBP2a and KAS III (Ki values in the submicromolar range). The characterized hop extract showed a good antimicrobial action with MICs ranging from 1 to 16 μg/mL and was able to inhibit the biofilm formation of all tested strains, except for two S. aureus strains. The biofilm formed in presence of the hop extract was significantly reduced in most cases, even when present at a concentration of 1/4 MIC. The live/dead images showed a remarkable inhibition in the biofilm formation by hop extract with a weak killing action. Overall, the tested hop extract is a good candidate to further explore for its use in the prevention of infection particularly, by multidrug-resistant Gram-positive pathogens.

Kiwi fruit samples (Actinidia deliciosa Planch, cv. Hayward) represent a suitable and good source for fibers obtainment as well as for polyphenolic and carotenoid extraction. With this aim, in this study they were submitted to a double phase extraction to separate insoluble fibers by an organic phase containing lipophilic substances and an hydroalcoholic phase containing polyphenols and soluble fibers. Insoluble fibers could be separated by filtration and sent to be micronized and reused. Hydroalcoholic fractions were then furtherly fractionated by solid-phase extraction. Data coming from the color CIEL*a*b* and the HPLC-DAD analyses of the extracts were compared and correlate with those coming from the SPME-GC/MS analysis of either the finely shredded peels or of the extracts. The obtained extracts were also submitted to anti-radical activity evaluation and anti-Candida activity. Results show that all of the obtained residues are value added products. Hypotheses were also made about the nature and the possible recycle of the obtained purified solid residue.

Mentha spicata is one of the most popular species in the genus, and it is of great interest as a gastrointestinal and sedative agent in the folk medicine system. In this study, different M. spicata extracts, obtained by the use of four solvents (hexane, chloroform, acetone and acetone/water) were chemically characterized using HPLC-ESI-MS n, which allowed for identification of 27 phenolic compounds. The extracts’ antioxidant and enzyme inhibitory properties were investigated. In addition, neuroprotective effects were evaluated in hypothalamic HypoE22 cells, and the ability of the extracts to prevent the hydrogen peroxide-induced degradation of dopamine and serotonin was observed. The best antioxidant effect was achieved for all the extraction methods using acetone/water as a solvent. These extracts were the richest in acacetin, eriodictyol, hesperidin, sagerinic acid, naringenin, luteolin, chlorogenic acid, chrysoeriol and apigenin. The intrinsic antioxidant and enzyme inhibition properties of the acetone/water extract could also explain, albeit partially, its efficacy in preventing prostaglandin E2 overproduction and dopamine depletion (82.9% turnover reduction) in HypoE22 cells exposed to hydrogen peroxide. Thus, our observations can provide a scientific confirmation of the neuromodulatory and neuroprotective effects of M. spicata.

In the present study, the phytochemical composition and bioactivities of A. maroccanus (AM) and A. radiatus (AR), two ecotypes collected in the Demnate road and Essaouira regions, respectively, were studied to highlight a pharmacological interest and to enable possible pharmaceutical development. To this end, methanolic and ethyl acetate extracts were prepared for each ecotype by fractionation; next, their phytochemical composition was evaluated by spectrophotometric and chromatographic analysis. Moreover, in line with the available evidence for Anacyclus spp. and their traditional use, a screening of bioactivities, including antioxidant, hypoglycemic, antiglycative, chelating, and antibacterial activities, was performed. The extracts were characterized by high amounts of polyphenols, tannins, and flavonoids, especially in the methanolic extracts; these samples were also enriched in carotenoids despite a lower chlorophyll content. Chlorogenic acid and rutin were the major identified compounds. The extracts also showed interesting hypoglycemic, antiglycative, and antibacterial properties, although with differences in efficacy and potency. Present results provide more scientific basis to the ethnopharmacological uses of Anacyclus spp. and suggest a further interest in AM and AR ecotypes as natural sources of bioactive compounds and/or phytocomplexes for possible pharmaceutical and nutraceutical developments.

The present work evaluates the aromatic waters of rosemary (Salvia rosmarinus Spenn. syn. Rosmarinus officinalis L.), sage (Salvia officinalis L.), and cypress (Cupressus sempervirens L.) obtained as innovative commercial products of a hydrodistillation process. All extracts were exhaustively analysed by GC-MS, 1H-NMR, and LC-MS in order to evaluate potential metabolite fingerprint differences. GC-MS appears to be the most exhaustive technique for the qualitative identification of the single constituents, although in this case, the use of 1H-NMR and LC-MS techniques allowed some useful considerations in semi-quantitative terms. Antimycotic effects were studied against Tricophyton, Candida, and Arthroderma species, resulting in weak activity. The toxicological impact was partly evaluated in vitro by means of allelopathy and brine shrimp lethality. Cytotoxicity was investigated in human colon cancer cells (HCT116) and in hypothalamic cells (Hypo-E22) challenged with hydrogen peroxide. Sage and rosemary hydrosols were the most effective antimycotics, whereas all hydrosols displayed antiradical effects. Cytotoxic effects against HCT116 cells (at 500 µL/mL) were related in silico to the endovanilloid TRPM8 and TRPV1 receptors. At lower concentrations (5–50 µL/mL), the hydrosols protected hypothalamic neurons Hypo-E22 cells from hydrogen peroxide-induced toxicity. The overall experience indicates that hydrolates are an important source of relevant phytochemicals with significant pharmacological potential.

In this study, the nutraceutical potential of two hazelnut varieties (Turkey and Italy) were examined by studying several aspects including the phytochemical properties, antioxidant potential, cell viability and ex vivo neuroprotective potential. Results showed that the Turkish hazelnut had the higher concentration of phenolic acids, flavonoids, higher antioxidant capacity and enzyme inhibition properties and lower saturated fatty acid concentration than the Italian sample. The in vivo studies showed that compared to the Italian hazelnuts, the addition of Turkish hazelnuts to high fat diet was associated with a more significant decrease in body weight, food consumption, atherogenic index, lipid peroxidation levels and biochemical/morphological markers of liver injury. Also, from our results, the two hazelnut varieties were protective against β-amyloid-induced neurochemical changes and high-fat diet induced alteration of metabolic indices.

The genus Pleurotus (Fr.) P. Kumm (Pleurotaceae, Basidiomycota) comprises a cosmopolitan group of mushrooms highly appreciated for their nutritional value and health-promoting benefits. Despite there being many studies about the phytochemical composition of Pleurotus spp., there are very few reports dealing with the phytochemistry, antioxidant and antimicrobial activities of P. columbinus Quél. In this study, a mass spectrometry ultra-performance liquid chromatography mass spectrometry (UHPLC)-QTOF method, coupled with principal component analysis (PCA), was applied to the P. columbinus metabolome in order to investigate the influence of different agri-food residues as growth substrates for P. columbinus cultivation, on the bioactive chemical profile of fruiting bodies and evaluated their potential as antioxidants and antimicrobials. Additionally, a quantitative HPLC-DAD-MS analysis was conducted on phenolic and flavonoid compounds, that could explain, albeit partially, the observed biological effects of P. columbinus extracts. The qualitative metabolic profile identified 97 metabolites, whereas the quantitative HPLC-DAD-MS analysis confirmed the presence of phenolic and flavonoids, in the mushroom extracts, which also showed intrinsic scavenging/reducing and antimicrobial effects. The antibacterial effects were particularly evident against Escherichia coli, whereas Tricophyton and Aspergillus were the dermatophytes more sensitive to the mushroom extracts. The present study supports more in-depth investigations, aimed at evaluating the influence of growth substrate on P. columbinus antimicrobial and antioxidant properties. The extracts from P. columbinus revealed valuable sources of primary and secondary metabolites, thus suggesting potential applications in the formulation of food supplements with biological properties, above all in terms of antioxidant and antimicrobial properties.

Hot air drying has proven to be an efficient method to preserve specific edible plant materials with medicinal properties. This is a process involving chemical, physical, and biological changes in plant matrices. Understanding these processes will lead to an improvement in the yields of bioactive compounds. This study aims to optimize the drying process of two species’ fruits used in folk medicine, Berberis vulgaris and Crataegus monogyna. The optimized extracts’ antioxidant capacity was assessed using various assays, with the barberry extract showing very good activity (50.85, 30.98, and 302.45 mg TE/g dw for DPPH, TEAC, and FRAP assays, respectively). Both species exerted good fungal α-glucosidase inhibitory activity (IC50 = 0.34 and 0.56 mg/mL, respectively) but no activity on mammalian α-glucosidase. Additionally, this study identified and quantified the main bioactive compounds. The results presented herein are a breakthrough in industrializing this drying process. Additional studies are necessary to mechanistically understand the drying process involved in these plant materials.

Vitis vinifera (grape) contains various compounds with acknowledged phytochemical and pharmacological properties. Among the different parts of the plant, pomace is of particular interest as a winemaking industry by-product. A characterization of the water extract from grape pomace from Montepulciano d’Abruzzo variety (Villamagna doc) was conducted, and the bioactive phenolic compounds were quantified through HPLC-DAD-MS analysis. HypoE22, a hypothalamic cell line, was challenged with an oxidative stimulus and exposed to different concentrations (1 µg/mL−1 mg/mL) of the pomace extract for 24, 48, and 72 h. In the same conditions, cells were exposed to the sole catechin, in a concentration range (5–500 ng/mL) consistent with the catechin level in the extract. Cell proliferation was investigated by MTT assay, dopamine release through HPLC-EC method, PGE2 amount by an ELISA kit, and expressions of neurotrophin brain-derived neurotrophic factor (BDNF) and of cyclooxygenase-2 (COX-2) by RT-PCR. The extract reverted the cytotoxicity exerted by the oxidative stimulus at all the experimental times in a dose-dependent manner, whereas the catechin was able to revert the oxidative stress-induced depletion of dopamine 48 h and 72 h after the stimulus. The extract and the catechin were also effective in preventing the downregulation of BDNF and the concomitant upregulation of COX-2 gene expression. In accordance, PGE2 release was augmented by the oxidative stress conditions and reverted by the administration of the water extract from grace pomace and catechin, which were equally effective. These results suggest that the neuroprotection induced by the extract could be ascribed, albeit partially, to its catechin content.

Despite the beneficial health properties shown by Lebanese saffron, its qualitative and quantitative composition has never been investigated before. In the present study, NMR spectroscopy, together with antioxidant activity assays, were applied to evaluate the chemical composition of saffron samples of different geographical origins (Lebanon, Italy, Iran, and India) and to categorize the Lebanese saffron for the first time. The distinction between Lebanese saffron and that produced in other countries was attributed to its higher linolenic and linoleic fatty acids, glucose and picrocrocin contents. Moreover, spices produced in three different regions of the Lebanese territory have been clearly differentiated. Saffron cultivated in the Qaa region displayed a high glucose, fatty acids and polyphenols content, whereas Hermel saffron exhibited the largest rate of picrocrocin and glycosylated carotenoids. Finally, samples from Baalbeck showed lower rates for the majority of metabolites. Moreover, Lebanese saffron showed a high antioxidant activity in ABTS and DPPH assays. A low dose of saffron extract (10 µg/mL) inhibited the growth of human lung adenocarcinoma cells, probably due to the high polyphenolic content. This study highlights the quality and peculiarity of Lebanese saffron cultivated in Northern Beqaa district and allows for a good discrimination between spices produced in relatively close territory.

Epilobium hirsutum is extensively used as a traditional remedy in folk medicine, especially against prostate inflammation. Therefore, we evaluated the chemical profiles and biopharmaceutical potentials of different extracts of E. hirsutum aerial parts and roots. Metabolomic, antioxidant, and enzyme inhibitory profiles were investigated. Human prostate cancer PC3 cells were exposed to the extracts to evaluate antiproliferative effects. Gene expression and bioinformatics analyses were performed to investigate anti-inflammatory mechanisms. Oenothein B and myricetin were prominent compounds in the extracts. In scavenging/reducing assays, the methanol, infusion, and methanol/water extracts exhibited similar activities. We also observed the reduction of PC3 viability occurring following exposure to methanol and methanol/water extracts. According to bioinformatics analysis, myricetin was predicted to interact with COX-2 and TNFα. The interaction between TNFα and oxo-dihydroxy-octadecenoic acid was predicted as well. Intriguingly, the gene expression of COX-2 and TNFα was reduced in PC3 cells after exposure to methanol and methanol/water extracts. These effects were paralleled by the decreased gene expression of IL-8 and NFkB and the inhibition of PGE2 release. Therefore, the present findings suggest the potential use of E. hirsutum for the management of the burden of inflammation and oxidative stress occurring in lower urinary tract diseases, including prostatitis.

The aim of the present study was to investigate the possible protective effects of a garlic hydroalcoholic extract on the burden of oxidative stress and inflammation occurring on mouse heart specimens exposed to E. coli lipopolysaccharide (LPS), which is a well-established inflammatory stimulus. Headspace solid-phase microextraction combined with the gas chromatography–mass spectrometry (HS-SPME/GC–MS) technique was applied to determine the volatile fraction of the garlic powder, and the HS-SPME conditions were optimized for each of the most representative classes of compounds. CIEL*a*b* colorimetric analyses were performed on the powder sample at the time of delivery, after four and after eight months of storage at room temperature in the dark, to evaluate the color changing. Freshly prepared hydroalcoholic extract was also evaluated in its color character. Furthermore, the hydroalcoholic extract was analyzed through GC–MS. The extract was found to be able to significantly inhibit LPS-induced prostaglandin (PG) E2 and 8-iso-PGF2α levels, as well as mRNA levels of cyclooxygenase (COX)-2, interleukin (IL)-6, and nuclear factor-kB (NF-kB), in heart specimens. Concluding, our findings showed that the garlic hydroalcoholic extract exhibited cardioprotective effects on multiple inflammatory and oxidative stress pathways.

Prunus mahaleb L. fruit has long been used in the production of traditional liqueurs. The fruit also displayed scavenging and reducing activity, in vitro. The present study focused on unravelling peripheral and central protective effects, antimicrobial but also anti-COVID-19 properties exerted by the water extract of P. mahaleb. Anti-inflammatory effects were studied in isolated mouse colons exposed to lipopolysaccharide. Neuroprotection, measured as a blunting effect on hydrogen-peroxide-induced dopamine turnover, was investigated in hypothalamic HypoE22 cells. Antimicrobial effects were tested against different Gram+ and Gram- bacterial strains. Whereas anti-COVID-19 activity was studied in lung adenocarcinoma H1299 cells, where the gene expression of ACE2 and TMPRSS2 was measured after extract treatment. The bacteriostatic effects induced on Gram+ and Gram- strains, together with the inhibition of COX-2, TNFα, HIF1α, and VEGFA in the colon, suggest the potential of P. mahaleb water extract in contrasting the clinical symptoms related to ulcerative colitis. The inhibition of the hydrogen peroxide-induced DOPAC/DA ratio indicates promising neuroprotective effects. Finally, the downregulation of the gene expression of ACE2 and TMPRSS2 in H1299 cells, suggests the potential to inhibit SARS-CoV-2 virus entry in the human host. Overall, the results support the valorization of the local cultivation of P. mahaleb.

Jatropha L. species, in particular, J. curcas and J. gossypiifolia, are well known medicinal plants used for treating various diseases. In the present study, leaf and stem bark extracts of J. curcas and J. gossypiifolia obtained by maceration or homogenizer assisted extraction, were investigated for their phytochemical contents and biological potential as antioxidants, enzyme inhibitors and neuromodulators. In this regard, the gene expression of tumor necrosis factor α (TNFα) and brain-derived neurotrophic factor (BDNF) was investigated in hypothalamic HypoE22 cells. Finally, a bioinformatics analysis was carried out with the aim to unravel the putative mechanisms consistent with both metabolomic fingerprints and pharmacological effects. The leaf extracts of J. curcas showed higher total phenolic content (TPC) and total flavonoid content (TFC) than the stem bark extracts (range: 5.79–48.95 mg GAE/g and 1.64–13.99 mg RE/g, respectively), while J. gossypiifolia possessed TPC and TFC in the range of 42.62–62.83 mg GAE/g and 6.97–17.63 mg RE/g, respectively. HPLC-MS/MS analysis revealed that the leaf extracts of both species obtained by homogenizer assisted extraction are richer in phytochemical compounds compared to the stem bark extracts obtained by the same extraction method. In vitro antioxidant potentials were also demonstrated in different assays (DPPH: 6.89–193.93 mg TE/g, ABTS: 20.20–255.39 mg TE/g, CUPRAC: 21.07–333.30 mg TE/g, FRAP: 14.02–168.93 mg TE/g, metal chelating activity: 3.21–17.51 mg EDTAE/g and phosphomolybdenum assay: 1.76–3.55 mmol TE/g). In particular, the leaf extract of J. curcas and the stem bark extract of J. gossypiifolia, both obtained by homogenizer assisted extraction, showed the most potent antioxidant capacity in terms of free radical scavenging and reducing activity, which could be related to their higher TPC and TFC. Furthermore, anti-neurodegenerative (acetylcholinesterase inhibition: 1.12–2.36 mg GALAE/g; butyrylcholinetserase inhibition: 0.50–3.68 mg GALAE/g), anti-hyperpigmentation (tyrosinase inhibition: 38.14–57.59 mg KAE/g) and antidiabetic (amylase inhibition: 0.28–0.62 mmol ACAE/g; glucosidase inhibition: 0.65–0.81 mmol ACAE/g) properties were displayed differentially by the different extracts. Additionally, the extracts were effective in reducing the gene expression of both TNFα and BDNF, which could be partially mediated by phenolic compounds such as naringenin, apigenin and quercetin. Indeed, the scientific data obtained from the present study complement the several other reports highlighting the pharmacological potentials of these two species, thus supporting their uses as therapeutically active plants.

Industrial hemp is characterized by a huge amount of by-products, such as inflorescences, that may represent high-quality sources of biomolecules with pharmaceutical interest. In the present study, we have evaluated the phytochemical profile, including terpene and terpenophenolic compounds, of the essential oils (EOs) of Futura 75, Carmagnola selezionata and Eletta campana hemp varieties. The EOs were also tested for antifungal properties toward Trichophyton mentagrophytes, Trichophyton rubrum, Arthroderma crocatum, Arthroderma quadrifidum, Arthroderma gypseum, Arthroderma curreyi, and Arthroderma insingulare. In parallel, we investigated the inhibitory effects of the EOs against tyrosinase, and the production of prostaglandin E2 in isolated mouse skin exposed to hydrogen peroxide. In human H1299 lung adenocarcinoma cells, we also evaluated the influence of the EOs on the gene expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2), which are involved in SARS-CoV-2 entry in human host. E-caryophyllene and α-pinene were the prominent terpenes in the EOs, whereas the cannabidiolic acid was the terpenophenol present at higher concentration. The EOs inhibited the growth of all tested dermatophytes species. In isolated skin specimens, EOs prevented the hydrogen-peroxide-induced synthesis of prostaglandin E2, consistent with the intrinsic antityrosinase activity. Finally, in H1299 cells, all tested EOs reduced the gene expression of ACE-2 and TMPRSS2, as well. Therefore, the present findings highlight the rationale for the use of the present EOs against infectious diseases.

Three specimens of H. officinalis subsp. aristatus were collected in three areas of the Abruzzo region (Italy) and subjected to macroscopic and microscopic observation to support their botanical identification. The essential oils (EOs) obtained from the aerial parts of the samples were characterized with the object to define their phytochemical and pharmaceutical biology profile. They highlight three different chemotypes, including one never seen in previous literature (CIV17-EO, distilled from sample harvested in 2017 at Civitaretenga), that showed a fingerprinting with the predominance of (-)-limonen-10-yl-acetate (67.9%). In 2017 European Food Safety Authority (EFSA) reported the genotoxicity of similar compounds, therefore, to dismiss any safety concern for the CIV17-EO use as flavouring substance, the Ames test was performed with no evidence of mutagenic activity. Safety of use coupled with chemical characterization of this new chemotype set the stage for a better standardization of H. officinalis EOs. The ethanolic extracts, on the other hand, with qualitatively similar chemical profiles in which caftaric, chlorogenic and rosmarinic acid were the main molecules, showed interesting antioxidant activity and a slight cytotoxicity towards the A549 cell line that could indicate a starting point for the evaluation of an additional preventive tool for maintaining health status.

Alchornea cordifolia (Schumach. & Thonn.) Müll. Arg. is a well-known African medicinal plant traditionally used for various healing purposes. In the present study, methanolic, ethyl acetate and infusion extracts of A. cordifolia leaves were studied for their total phenolic and flavonoid contents and screened for their chemical composition. Moreover, the enzyme (acetyl- and butyryl-cholinesterases, α-amylase, α-glucosidase, and tyrosinase) inhibitory and cytotoxicity activities on HepG2: human hepatocellular carcinoma cells, B16 4A5: murine melanoma cells, and S17: murine bone marrow (normal) cells of extracts were evaluated. Finally, components-targets and docking analyzes were conducted with the aim to unravel the putative mechanisms underlying the observed bio-pharmacological effects. Interestingly, the infusion and methanolic extracts showed significantly higher total phenolic and flavonoid contents compared with the ethyl acetate extract (TPC: 120.38–213.12 mg GAE/g and TFC: 9.66–57.18 mg RE/g). Besides, the methanolic extracts followed by the infusion extracts were revealed to contain a higher number of compounds (84 and 74 compounds, respectively), while only 64 compounds were observed for the ethyl acetate extract. Gallic acid, ellagic acid, shikimic acid, rutin, quercetin, myricetin, vitexin, quercitrin, kaempferol, and naringenin were among the compounds that were commonly identified in all the studied extracts. Additionally, the methanolic and infusion extracts displayed higher antioxidant capacity than ethyl acetate extract in all assays performed. In ABTS and DPPH radical scavenging assays, the methanol extract (500.38 mg TE/g for DPPH and 900.64 mg TE/g for ABTS) exhibited the best ability, followed by the water and ethyl acetate extracts. Furthermore, the extracts exhibited differential enzyme inhibitory profiles. In particular, the methanolic and infusion extracts showed better cytotoxic selectivity activity against human hepatocellular carcinoma cells. Overall, this study demonstrated A cordifolia to be a species worthy of further investigations, given its richness in bioactive phytochemicals and wide potentialities for antioxidants and pharmacological agents.

Industrial hemp is a multiuse crop that has been widely cultivated to produce fibers and nutrients. The capability of the essential oil (EO) from inflorescences as antimicrobial agent has been reported. However, literature data are still lacking about the hemp EO antiprotozoal efficacy in vivo. The present study aims to unravel this concern through the evaluation of the efficacy of hemp EOs (2.5 mL/kg, intraperitoneally) of three different cultivars, namely Futura 75, Carmagnola selezionata and Eletta campana, in mice intraperitoneally infected with Leishmania tropica. A detailed description of EO composition and targets-components analysis is reported. Myrcene, α-pinene and E-caryophyllene were the main components of the EOs, as indicated by the gas-chromatographic analysis. However, a prominent position in the scenario of the theoretical interactions underlying the bio-pharmacological activity was also occupied by selina-3,7(11)-diene, which displayed affinities in the micromolar range (5.4–28.9) towards proliferator-activated receptor α, cannabinoid CB2 receptor and acetylcholinesterase. The content of this compound was higher in Futura 75 and Eletta campana, in accordance with their higher scavenging/reducing properties and efficacy against the tissue wound, induced by L. tropica. Overall, the present study recommends hemp female inflorescences, as sources of biomolecules with potential pharmacological applications, especially towards infective diseases.

To avail the possible pharmacological actions of Brideliaferruginea Benth., the present investigation was designed to quantitatively analyze the total flavonoid and phenolic contents and assess the various antioxidant and enzyme inhibition properties of leaf and stem bark extracts (ethyl acetate, water and methanolic) of B. ferruginea. Anti-proliferative effect was also investigated against human colon cancer cells (HCT116) as well as the antimicrobial potential against multiple bacterial and fungal (yeasts and dermatophytes) strains. The methanolic and water extracts of the stem bark demonstrated the highest phenolic content (193.58 ± 0.98 and 187.84 ± 1.88 mg/g, respectively), while the leaf extracts showed comparatively higher flavonoid contents (24.37–42.31 mg/g). Overall, the methanolic extracts were found to possess the most significant antioxidant potency. Compared to the other extracts, methanolic extracts of the B. ferruginea were revealed to be most potent inhibitors of acetyl- and butyryl-cholinesterases, tyrosinase α-amylase, except α-glucosidase. Only the ethyl acetate extracts were found to inhibit glucosidase. Additionally, the stem bark methanolic extract also showed potent inhibitory activity against E. coli and gram-positive bacteria (MIC (minimum inhibitory concentration): 2.48–62.99 µg/mL), as well as all the tested fungi (MIC: 4.96–62.99 µg/mL). In conclusion, B. ferruginea can be regarded as a promising source of bioactive compounds displaying multifunctional pharmacological activities and thus is a potential candidate for further investigations in the endeavor to develop botanical formulations for pharmaceutical and cosmeceutical industries.

Industrial hemp is a multiuse crop whose phytocomplex includes terpenophenolics and flavonoids. In the present study, the phenolic and terpenophenolic compounds were assayed in the water extract of the hemp variety Futura 75. Protective effects were also investigated in human fibroblast and keratinocytes and isolate mouse skin specimens, which were exposed to hydrogen peroxide and/or to the extract (1–500 µg/mL). The results of phytochemical analysis suggested the cannabidiol, cannabidiolic acid and rutin as the prominent phytocompounds. In the in vitro system represented by human keratinocytes and fibroblasts, the hemp extract was found to be able to protect cells from cytotoxicity and apoptosis induced by oxidative stress. Moreover, modulatory effects on IL-6, a key mediator in skin proliferation, were found. In isolated rat skin, the extract reduced hydrogen peroxide-induced l-dopa turnover, prostaglandin-E2 production and the ratio kynurenine/tryptpophan, thus corroborating anti-inflammatory/antioxidant effects. The in silico docking studies also highlighted the putative interactions between cannabidiol, cannabidiolic acid and rutin with tyrosinase and indoleamine-2,3-dioxygenase, involved in l-dopa turnover and tryptophan conversion in kynurenine, respectively. In conclusion, the present findings showed the efficacy of hemp water extract as a skin protective agent. This could be partly related to the extract content in cannabidiol, cannabidiolic acid and rutin.

Tanacetum parthenium (feverfew) has traditionally been employed as a phytotherapeutic remedy in the treatment of migraine. In this study, a commercial T. parthenium water extract was investigated to explore its anti-inflammatory and neuromodulatory effects. Isolated mouse cortexes were exposed to a K+ 60 mM Krebs-Ringer buffer and treated with T. parthenium water extract. The prostaglandin E2 (PGE2) level, brain-derived neurotrophic factor (BDNF), interleukin-10 (IL-10), and IL-1β gene expression were evaluated in the cortex. The effects on dopamine (DA) release and dopamine transporter (DAT) gene expression were assayed in hypothalamic HypoE22 cells. A bioinformatics analysis was conducted to further investigate the mechanism of action. The extract was effective in reducing cortex PGE2 release and IL-1β gene expression. In the same experimental system, IL-10 and BDNF gene expressions increased, and in HypoE22 cells, the extract decreased the extracellular dopamine level and increased the DAT gene expression due to the direct interaction of parthenolide with the DAT. Overall, the present findings highlight the efficacy of T. parthenium water extract in controlling the inflammatory pathways that occur during cortical-spreading depression. Additionally, the inhibition of the hypothalamic DA release observed in this study further supports the role of dopaminergic pathways as key targets for novel pharmacological approaches in the management of migraine attacks.

Nine commercial hemp seed oils from different countries were studied using a multimethodological approach to obtain information about their quality and chemical composition. Due to the lack of a specific regulation for hemp seed oils, quality parameters used in the case of olive oils (free acidity, peroxides number, spectrophotometer parameters) and anisidine number were measured and compared with those reported for extra virgin olive oil (EVOO). Free acidity and peroxides number showed a great variability, ranging from 0.4 to 17.24% and from 4.32 to 22.14 meqO2/kg, respectively, whereas the anisidine number ranged from 0.11 to 3.58. K232 value turned out to be generally below the limit reported for EVOO, whereas K270 and ΔK values were higher, with respect to EVOO limits, due to the high amount of tri-unsaturated fatty chains. Colorimetric analysis showed a peculiar curve trend that could represent the fingerprint of this product. Untargeted nuclear magnetic resonance methodology allowed to measure the amount of fatty chains, ω-6:ω-3 ratio, β-sitosterol, and aldehydes. The ω-6:ω-3 ratio turned out to be, in some cases, different from that reported on the bottle labels. Finally, lipoperoxidation assays were also carried out under different storage (light and temperature) and time exposure conditions, confirming that the exposure to direct light is the condition that interferes more with the product quality.

Coronilla species, belonging to the Coronilla genus (Fabaceae), have long been used in traditional medicine for treating cold, diabetes, pain, and as cardiotonics. The goal of the present study was to explore the phytochemical composition and pharmaco-toxicological properties of C. minima. In this regard, phenolic content, scavenging/reducing properties and antimicrobial activity toward pathogen bacterial (Escherichia coli, Pseudomonas aeruginosa, Bacillus cereus, Staphylococcus aureus) and fungal strains (Candida albicans, C. tropicalis, Aspergillus tubigensis and A. minutus) were investigated. Extract effects on human colon cancer HCT116 cell viability were also assayed. Finally, a bioinformatics approach was conducted with the aim to identify putative microbial and human protein targets underlying antibacterial, antimycotic, and antiproliferative effects. Phytochemical investigation suggested that water extract is richer in terms of total flavonoid and phenol content, whereas the hydroalcoholic extract was revealed to be more potent as antioxidant agent. According to bioinformatics analysis, the antibacterial activity of the hydroalcoholic extract could be related to its content in resveratrol. The presence of resveratrol could also explain the hydroalcoholic extract efficacy in reducing HCT116 cell viability. In conclusion, the present study represents the first phytochemical and bio-pharmacological investigation about C. minima. Like other plants belonging to the Fabaceae family, C. minima revealed a good source of resveratrol, which could explain, albeit partially, the efficacy of the hydroalcoholic extract as antimicrobial, antioxidant, and antiproliferative agent.

Tricholosporum goniospermum (Bres.) Guzmán ex T.J. Baroni is an excellent edible mushroom whose compounds and biological properties are still unknown. In this study, n-hexane, ethyl acetate and methanol extracts from fruiting bodies and liquid-cultured mycelia were compared for the analysis of phenolic compounds, the evaluation of scavenger (DPPH, ABTS) and reducing (CUPRAC, FRAP) activities, and the enzyme inhibition of α-amylase, acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and tyrosinase. Additionally, T. goniospermum extracts were evaluated for antibacterial and antimycotic activities against Gram+ and Gram− bacteria, and clinical yeast and fungal dermatophytes. Finally, based on the extract content in phenolic compounds, in silico studies, including the docking approach, were conducted to predict the putative targets (namely tyrosinase, lanosterol-14-α-demethylase, the multidrug efflux system transporters of E. coli (mdtK) and P. aeruginosa (pmpM), and S. aureus β-lactamase (ORF259)) underlying the observed bio-pharmacological and microbiological effects. The methanolic extract from mycelia was the richest in gallic acid, whereas the ethyl acetate extract from fruiting bodies was the sole extract to show levels of catechin. Specifically, docking runs demonstrated an affinity of catechin towards all docked proteins, in the micromolar range. These in silico data are consistent, at least in part, with the highest activity of ethyl acetate extract as an antimicrobial and anti-tyrosinase (554.30 mg KAE/g for fruiting bodies and 412.81 mg KAE/g for mycelia) agent. The ethyl acetate extracts were also noted as being the most active (2.97 mmol ACAE/g for fruiting bodies and 2.25 mmol ACAE/g for mycelia) on α-amylase. BChE inhibitory activities varied from 2.61 to 26.78 mg GALAE/g, while the tested extracts were not active on AChE. In conclusion, all mushroom extracts tested in this study had potent antimicrobial activities. Particularly, among the tested extracts, the ethyl acetate extract showed the highest efficacy as both an antimicrobial and anti-tyrosinase agent. This could be related, albeit partially, to its content of catechin. In this regard, the bioinformatics analyses showed interactions of catechin with tyrosinase and specific microbial proteins involved in the resistance to chemotherapeutic drugs, thus suggesting innovative pharmacological applications of T. goniospermum extracts.

Strawberries belonging to cultivar Clery (Fragaria x ananassa (Duchesne ex Weston)), cultivated in central Italy were subjected to a multi-methodological experimental study. Fresh and defrosted strawberries were exposed to different processing methods, such as homogenization, thermal and microwave treatments. The homogenate samples were submitted to CIEL*a*b* color analysis and Head-Space GC/MS analysis to determine the impact of these procedures on phytochemical composition. Furthermore, the corresponding strawberry hydroalcoholic extracts were further analyzed by HPLC-DAD for secondary metabolites quantification and by means of spectrophotometric in vitro assays to evaluate their total phenolic and total flavonoid contents and antioxidant activity. These chemical investigations confirmed the richness in bioactive metabolites supporting the extraordinary healthy potential of this fruit as a food ingredient, as well as functional food, highlighting the strong influence of the processing steps which could negatively impact on the polyphenol composition. Despite a more brilliant red color and aroma preservation, non-pasteurized samples were characterized by a lower content of polyphenols and antioxidant activity with respect to pasteurized samples, as also suggested by the PCA analysis of the collected data.

Even though Salvia genus is one of the most known and studied taxa of Lamiaceae family, the knowledge regarding the chemical composition and health-related benefits of some locally used Salvia species (mostly endemic) is still scarce. In this regard, the present work aims to evaluate the chemical profile and potential bioactivities of 70% (v/v) ethanolic extracts obtained from the less-studied S. transsylvanica and S. glutinosa in comparison with S. officinalis. HPLC-PDA analysis revealed the presence of rutin and catechin as the main compounds in the extracts of the three studied species (using the employed HPLC method), whereas the presence of naringenin was highlighted only in S. glutinosa extract. Chlorogenic acid, rutin and quercetin were identified and quantified for the first time in S. transsylvanica extracts. The in vitro antioxidant capacity of each extract was tested through complementary methods (phosphomolybdenum assay, DPPH, ABTS, CUPRAC and FRAP assays), and correlated with the presence of phenolics (especially flavonoids) in high amounts. The neuroprotective and antidiabetic abilities of S. officinalis (the most active as AChE, BChE and α-glucosidase inhibitor), S. glutinosa (the most active as α-amylase inhibitor) and S. transsylvanica were also studied. For each extract it was determined the antimicrobial, antifungal and cytotoxic effects using in vitro assays. The obtained results confirm the potential of S. transsylvanica and S. glutinosa as promising sources of bioactive compounds and as a starting point for further analyses.

Mangrove forests exemplify a multifaceted ecosystem since they do not only play a crucial ecological role but also possess medicinal properties. Methanolic, ethyl acetate and aqueous leaf and bark extracts were prepared using homogenizer-assisted extraction (HAE), infusion and maceration (with and without stirring). The different extracts were screened for phytochemical profiling and antioxidant capacities in terms of radical scavenging (DPPH, ABTS), reducing potential (CUPRAC, FRAP), total antioxidant capacity and chelating power. Additionally, R. racemosa was evaluated for its anti-diabetic (α-amylase, α-glucosidase), anti-tyrosinase and anti-cholinesterase (AChE, BChE) activities. Additionally, antimycotic and antibacterial effects were investigated against Eescherichia coli, Pseudomonas aeruginosa, Salmonella typhimurium, Listeria monocytogenes, Enterobacter cloacae, Bacillus cereus, Micrococcus luteus, Staphylococcus aureus, Aspergillus fumigatus, Aspergillus niger, Trichoderma viride, Penicillium funiculosum, Penicillium ochrochloron and Penicillium verrucosum. Finally, based on phytochemical fingerprint, in silico studies, including bioinformatics, network pharmacology and docking approaches were conducted to predict the putative targets, namely tyrosinase, lanosterol-14-α-demethylase and E. coli DNA gyrase, underlying the observed bio-pharmacological and microbiological effects. The methanolic leave and bark extracts (prepared by both HAE and maceration) abounded with phenolics, flavonoids, phenolic acids and flavonols. Results displayed that both methanolic leaf and bark extracts (prepared by HAE) exhibited the highest radical scavenging, reducing potential and total antioxidant capacity. Furthermore, our findings showed that the highest enzymatic inhibitory activity recorded was with the tyrosinase enzyme. In this context, bioinformatics analysis predicted putative interactions between tyrosinase and multiple secondary metabolites including apigenin, luteolin, vitexin, isovitexin, procyanidin B, quercetin and methoxy-trihydroxyflavone. The same compounds were also docked against lanosterol-14α-demethylase and E. Coli DNA gyrase, yielding affinities in the submicromolar–micromolar range that further support the observed anti-microbial effects exerted by the extracts. In conclusion, extracts of R. racemosa may be considered as novel sources of phytoanti-oxidants and enzyme inhibitors that can be exploited as future first-line pharmacophores.

Anacamptis pyramidalis (L.) Rich. forms part of the Orchidaceae family that is highly valued for its horticultural as well as therapeutic benefits. The present study set out to investigate the inhibitory activity of A. pyramidalis tubers against key biological targets for the management of type 2 diabetes, Alzheimer disease, and skin hyperpigmentation. In addition, the antioxidant potential of the extracts was also assessed using multiple methods. The detailed phytochemical profiles of the extracts were determined using high-performance liquid chromatography. Based on qualitative phytochemical fingerprint, a network pharmacology analysis was conducted as well. Parishin was identified from the water extract only, whereas gastrodin and caffeic acid derivatives were present in the methanol extract. The methanol extract exhibited high inhibitory activity against tyrosinase (69.69 mg kojic acid equivalent/g extract), α-amylase (15.76 mg acarbose equivalent/g extract), and α-glucosidase (20.07 mg acarbose equivalent/g extract). Similarly, the methanol extract showed highest antioxidant potential (22.12, 44.23, 45.56, and 29.38 mg Trolox equivalent/g extract, for 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), CUPric Reducing Antioxidant Capacity (CUPRAC), and Ferric Reducing Antioxidant Power (FRAP) assays, respectively). Finally, the results of network pharmacology analysis, besides corroborating traditional uses of plant extracts in the management of cold and flu, confirmed a direct involvement of identified phytochemicals in the observed enzyme inhibitory effects, especially against tyrosinase, α-amylase, and α-glucosidase. Furthermore, based on the results of both colorimetric assays and network pharmacology analysis related to the activity of A. pyramidalis extracts and identified phytocompounds on enzymes involved in type 2 diabetes, a docking study was conducted in order to investigate the putative interactions of oxo-dihydroxy octadecenoic acid trihydroxy octadecenoic acid against aldose reductase, peroxisome proliferator-activated receptor (PPAR)-α, dipeptidyl peptidase (DPP)-IV, and α-glucosidase. Docking analysis suggested the inhibitory activity of these compounds against the aforementioned enzymes, with a better inhibitory profile shown by oxo-dihydroxy octadecenoic acid. Overall, the present findings supported the rationale for the use of A. pyramidalis as source of bioactive metabolites and highlight, today more than ever, for the strong necessity of linkage strategy between wild resource valorization and conservation policy.

The present work evaluates for the first time two Lavandin (Lavandula × intermedia Emeric ex Loisel.) aromatic waters obtained from different plant organs, the flowers and the stems. Both extracts were analysed by GC-MS, which indicates semi-quantitative differences between the major metabolites including linalool, 1,8-cineole, camphor, linalyl acetate and 4-terpineol. 1H-NMR and LC-MS investigation confirmed the presence of these compounds. Moreover, behavioural tests with the food insect pest Tribolium confusum (Coleoptera Tenebrionidae) showed a good repellency for both hydrosols extracts with RD50 values of 3.6 and 3.3 µL·cm−2 for the flowers and stems, respectively; at the higher concentrations, however, the hydrosol extract from the flowers is expected to be more effective than the one from the stems. The effect of the flowers and stems aromatic water of Lavandin on seed germination of Raphanus sativus was also evaluated. Results showed that seed germination was completely inhibited by flowers hydrolate, having a possible application as natural herbicide. The overall experience with these Lavandin extracts indicates the potential of improved hydrolates to become the main distillation products, rather than by-products, of the aromatic plants manufacturing; this stimulates further discussions about the potential positive impacts that such a shift could have in the context of ecopharmacognosy.