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Lunaria annua is an underexplored crop with promising potential for use in various industries: food, oil etc. It grows rapidly, has low maintenance and high resistance to pathogens, which makes it a promising crop for sustainable cultivation. Herein, we investigated nutritional value, phenolic profile, and bioactive properties of L. annua seeds collected in the wild. The results we obtained indicate that seeds of L. annua have high energy value (406.6 kcal/100 g dw), with high share of carbohydrates (65.2 g/100 g dw), followed by proteins (26.47 g/100 g dw) and fat (4.46 g/100 g dw). Free sugar analysis showed presence of fructose, glucose and sucrose (0.77 g, 0.189 g and 3.85 g/100 g dw, respectively). Oxalic and malic acid were quantified <1.0 g/100 g dw and fumaric acid only in trace. Monounsaturated fatty acids were predominant over polyunsaturated and saturated fatty acids (erucic, nervonic and oleic acid were dominant). The content of flavonoid compounds was several times higher than the content of phenolic acids (58.5 vs 9.4 mg/g). Methanolic extract showed better antioxidant potential than dichloromethane extract (EC 50  = 0.32 vs. 1.25 mg/mL, in TBARS test). The antibacterial activity ranged from 0.50 to 2.00 mg/mL, with E. coli showing the highest susceptibility to the methanolic extract (MIC: 0.25 mg/mL, MBC: 0.50 mg/mL). The other tested microorganisms showed quite uniform susceptibility to the extracts, but better than the positive controls E211 and E224. The tested samples demonstrated encouraging antifungal/anticandidal properties, and no cytotoxic effects onto spontaneously immortalized keratinocytes cell line HaCaT, indicating its safe application in terms of dermal exposure. Overall, our results indicate that L. annua seeds may be considered as source of compounds used in food and pharmaceutical industry and a candidate for functional ingredient that provides additional health benefits beyond basic nutritional requirements., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Corresponding author Dejan Stojković serves as Associate Editor of the journal Heliyon. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2025 The Authors. Published by Elsevier Ltd.)

Background/objectives: Cotinus coggygria Scop. is traditionally used for treatment of various gastrointestinal ailments. In this study, we investigated the phytochemical profile and biological activities of leaves, bark and flowers extracts of C. coggygria. Methods: Phytochemical analysis was performed using HPLC. The antimicrobial activity of water and methanolic extracts of C. coggygria leaves, bark and flowers towards various oral fungal and bacterial strains of clinical origin was tested by use of a microdilution assay. Additionally, their cytotoxic activity was determined against different gastrointestinal carcinoma cell lines (CAL27, FaDu, SW480, HCT116 and MRC-5) in concentrations ranging from 3.125 to 400 µg/mL for 48 and 72 h., Results: The presence of numerous flavonoid and phenolic compounds such as sulfuretin, gallic acid, rutin, hyperoside, and isoquercitrine was detected. Micrococcus luteus , Streptococcus parasanguinis , and Candida tropicalis were the most sensitive microbiological species, with MICs of 0.12 mg/mL for the most effective extracts. Additionally, the cytotoxic activity of the samples against different gastrointestinal carcinoma cell lines (CAL27, FaDu, SW480, HCT116, and MRC-5) was determined in concentrations ranging from 3.125 to 400 µg/mL. Among the tested samples, the methanolic leaf extract exhibited the highest cytotoxic capacity, and the possible mechanism could be related to its inhibitory effect on the release of proinflammatory cytokine in CD4+ cells., Conclusions: The traditional use of C. coggygria for gastrointestinal diseases may be substantiated by its ability to inhibit the growth of harmful microorganisms and its promising cytotoxic properties. The methanolic leaf and flower extracts show significant potential for future clinical applications, and further studies are warranted to explore their mechanisms and applications in medical treatments.

Alhagi persarum (AP), Alhagi persarum flowers (APF), Ephedra equisetina (EE) and Glycyrrhiza glabra root (GGR) have been utilized in Central Asian folk medicine for centuries. In the present study, antioxidant, enzyme inhibition, antimicrobial and cytotoxic effects the aqueous extracts of these plants were studied. In addition, 23 compounds were identified in the extracts using UHPLC-DAD-QqQ-MS/MS analysis. The four plant samples demonstrated promising antioxidant activities in vitro for scavenging of 2, 20-azinobis-(3-ethylbenz-thiazoline-6-sulphonate) radical (ABTS), 1, 1-diphenyl-2-picrylhydrazyl radical (DPPH), and total reducing power. AP (DPPH: 47.39 mg TE/g; ABTS:108.58 mg TE/g; CUPRAC: 117.41 mg TE/g; FRAP: 82.22 mg TE/g) and EE (DPPH: 46.75 mg TE/g; ABTS: 110.51 mg TE/g; CUPRAC: 140.77 mg TE/g; FRAP: 91.00 mg TE/g) displayed the strongest antiradical and reduction abilities in the test system. In terms of enzyme inhibition efficacy, AP and EE showed higher bioactivity. Aqueous extracts demonstrated the most potent efficacy against eight different bacterial and fungal strains in antibacterial (MIC values: 1.5-4 mg/ml) and antifungal (MIC values: 1-8 mg/ml) testing. Contrary to other activities, these aqueous extracts did not show cytotoxic effects against HaCaT cells. All bioactivities suggested that the plants could be utilized as candidate resources in the food and pharmaceutical industries., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Jujube ( Ziziphus jujuba Mill.) is a highly abundant wild-growing plant in Montenegro. It has been utilized since old times for various bioactive properties by the natives, however its detailed chemical characterization, antimicrobial, antioxidant and cytotoxic potential have not been extensively explored. Herein, we used crud methanol extract and three fractions (methylene chloride, n -butanol and aqueous) to asses bioactive features of fruits from this wild growing edible plant, after which we performed the targeted analysis of phenolic compounds of n -butanol fraction by (UHPLC-DAD-MS/MS). Our antioxidant assays showed the highest radical scavenging potential for n -butanol fraction using DPPH and ABTS methods. As for the antimicrobial activity of extract and three fractions, generally aqueous showed the least promising antibacterial and antifungal properties, whereas methylene chloride, methanol and n -butanol fractions showed quite promising antimicrobial potential. E. coli and S. aureus strains were the most susceptible to the compounds present in the methylene chloride and n -butanol fractions with MIC of 0.01-0.025 mg/mL, and MBC 0.025-0.05 mg/mL, along with MRSA strain, which was the most susceptible to the effects of methanol extract with MIC of 0.10 mg/mL and MBC 0.15 mg/mL. The results of antifungal activity showed lower potential to inhibit growth of pathogenic fungi than bacteria, whereas cytotoxicity assay showed extracts have no effects towards HaCaT skin cell line.The n -butanol fraction had the overall most promising activity, and therefore was subjected to more in depth chemical analysis., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Corresponding author Dejan Stojković serves as Associate Editor of the journal Heliyon. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

In this study, we conducted a thorough analysis of Rheum turkestanicum (RT) and Calendula officinalis flowers (COF) extracts with varying polarities using LC-MS chemical profiling and biological tests (antioxidant, antimicrobial, enzyme inhibition, and cytotoxic effects). The highest level of total phenolic content in the ethanol extract of RT with 75.82 mg GAE/g, followed by the infusions of RT (65.00 mg GAE/g) and COF (40.99 mg GAE/g). A total of 20 bioactive compounds were identified and quantified. The ethanol extract of COF was rich in terms of 5-O-caffeoylquinic acid (2780.56 μg/g), isorhamnetin-O-rutinoside (1653.59 μg/g), and rutin (1356.97 μg/g). However, RF extracts were rich in catechin gallate (21.66-80.01 μg/g) and 5-O-caffeoylquinic acid. Except for metal chelating ability, the ethanol extract of RT exhibited the strongest ability (DPPH: 171.5 mg TE/g; ABTS: 387.35 mg TE/g; CUPRAC: 449.80 mg TE/g; FRAP: 195.60 mg TE/g; and PBD: 1.52 mmol TE/g). In the enzyme inhibition tests, the tested ethanol extracts for both species were more active than the infusion. The highest values for tyrosinase were recorded as 72.47 mg KAE/g (in RT extracts) and 71.74 mg KAE/g (in COF extracts). Furthermore, all extracts underwent assessment for their antibacterial and antifungal properties, targeting both Gram-positive and Gram-negative bacteria, as well as clinical yeast and fungal microorganisms. In silico studies yielded valuable insights into the potential therapeutic applications of the bioactive compounds identified in COF and RT extracts. Stable interactions were observed between key compounds, such as isorhamnetin 3-O-glucoside and 3-O-caffeoylquinic acid, with crucial target proteins (AChE, BChE, and MurE). These compounds formed stable hydrogen bonds with minimal root mean square deviation (RMSD) fluctuations, particularly in the isorhamnetin 3-O-glucoside- Staphylococcus aureus MurE and 3-O-caffeoylquinic acid-MurE of S. aureus complexes. These findings further underscore the potential of these compounds as promising candidates for therapeutic development., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Food Science & Nutrition published by Wiley Periodicals LLC.)

This study was designed to investigate chemical composition and biological activities of the Anthriscus cerefolium methanolic extract. Chemical characterization of the extracts was performed by LC-HRMS/MS analysis. Antimicrobial activities of the extract were investigated on six bacteria and eight fungi while antioxidant activity was assessed by six different assays. Anti-enzymatic activity of the methanolic extract was tested on five enzymes associated with therapy of neurodegenerative diseases and diabetes mellitus type 2. Cytotoxic properties of the extract were tested on human immortalized keratinocytes (HaCaT) and tumor cell lines (SiHa, MCF7, HepG2). Anti-inflammatory activity of the extract was assessed on bacteria mediated inflammation model using HaCaT cell line. Molecular docking studies of enzymes and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis were performed. The results showed that the obtained extract was rich in phenolic compounds (a total of seventy-two were identified), with malonyl-1,4-O-dicaffeoylquinic acid and 3,5-O-dicaffeoylquinic acid dominating in the sample. The extract expressed antimicrobial, antioxidant, anti-enzymatic, cytotoxic and anti-inflammatory properties. The identified compounds demonstrated strong binding to the acetylcholinesterase (AChE) and to a lesser extent, to the butyrylcholinesterase (BChE), glucosidase, amylase, and modestly, to tyrosinase. KEGG pathway analysis has shown that the certain phenolic compounds may be related to anti-tumor, anti-inflammatory and anti-microbial activities of the extract. The data obtained suggest that phenolic compounds of the extract and their mixtures should be considered for future research as ingredients in pharmaceutical and nutraceutical formulations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Herein we describe the antioxidant, antimicrobial, antibiofilm, anti-inflammatory and wound-healing potential of aqueous and polysaccharide extracts from three widely appreciated mushrooms: Agrocybe aegerita , Laetiporus sulphureus and Agaricus bisporus . Moreover, we present their detailed phenolic, polysaccharide and protein profiles and ATR-FTIR spectra. The study found that polysaccharide extracts (PEs) from mushrooms had higher total and β -glucan levels than aqueous extracts (AEs), with A. aegerita showing the highest content. L. sulphureus had a higher total protein content, and A. aegerita AE had the highest phenolic content. Our results indicate that all the tested extracts have high potential regarding their bioactive properties, with A. aegerita being the most promising one. Namely, the antibacterial activity assay showed that the development of the skin-infection-causing agent, Staphylococcus aureus , was inhibited with a minimal inhibitory concentration of 4.00 mg/mL and minimal bactericidal concentration of 8.00 mg/mL, while the results regarding wound healing showed that, over the course of 24 h, the A. aegerita extract actively promoted wound closure in the HaCaT keratinocyte cell line model. The anti-inflammatory activity results clearly showed that when we used S. aureus as an inflammation-inducing agent and the A. aegerita aqueous extract in treatment, IL-6 levels reduced to the level of 4.56 pg/mL. The obtained data suggest that the tested mushroom extracts may serve as a source of bioactive compounds, with potential applications in the cosmeceutical, pharmaceutical and food industries. Furthermore, potential skin preparations carefully crafted with mushroom extract may help restore the skin's barrier function, decrease the probability of staph infections and minimize skin irritation.

Wild edible greens are a key ingredient of the so-called Mediterranean diet and they are commonly used in various local dishes in their raw or processed form. Domestic processing of edible greens may affect their nutritional value and chemical profile. In this work, six wild species (e.g., Cichorium spinosum L. (S1); Centaurea raphanina subsp. mixta (DC.) Runemark (S2); Picris echioides (L.) Holub (S3); Urospermum picroides (L.) Scop. ex. F.W. Schmidt (S4); Sonchus oleraceus L. (S5); and S. asper L. (S6)) were assessed for the effect of domestic processing (boiling) on chemical composition and bioactivities. Concerning the chemical composition, glucose, oxalic acid, α-tocopherol, and α-linolenic acid were the most abundant compounds, especially in P. echiodes leaves. After decoction, mainly sugars, tocopherols, and oxalic acid were decreased. The species and processing affected the phenolic compounds content and antioxidant, cytotoxicity, and anti-inflammatory activities. Specific compounds were not previously detected in the studied species, while hydroethanolic extracts contained a higher total phenolic compound content. Hydroethanolic and aqueous extracts were effective towards a range of bacterial and fungi strains. Therefore, the consumption of leaves has health-promoting properties owing to the bioactive compounds and can be integrated into healthy diets. However, domestic cooking may affect the chemical profile and bioactivities of the edible leaves, especially in the case of free sugars and phenolic compound content where a significant reduction was recorded in leaves after decoction. On the other hand, domestic processing could be beneficial since it reduces the oxalic acid content in edible leaves, which is considered an antinutritional factor.

In order to gain further insight into how various extraction techniques (maceration, microwave-, and ultrasound-assisted extractions) affect the chemical profile and biological activities of leaf extracts from Paeonia tenuifolia L., Paeonia peregrina Mill., and Paeonia officinalis L., this research was performed. The targeted chemical characterization of the extracts was achieved using the Ultra-High-Performance-Liquid-Chromatography-Linear-Trap-Mass-Spectrometry OrbiTrap instrumental technique, while Fourier Transform Infrared Spectroscopy was conducted to investigate the structural properties of the examined leaf extracts. According to the results, the species P. officinalis, Božurna locality as the origin of the plant material, and microwave-assisted extraction produced the maximum polyphenol yield, (491.9 ± 2.7 mg gallic acid equivalent (GAE)/mL). The ethanolic extracts exhibited moderate antioxidant activity as evaluated by DPPH (2,2-diphenyl-1-picrylhydrazyl) and phosphomolybdenum tests. With MIC values of 0.125 mg/mL, the leaf extracts produced by ultrasound-assisted extraction and maceration (Deliblato sands and Bogovo gumno) had the best antibacterial activity against Pseudomonas aeruginosa and Salmonella Typhimurium. Ultrasound-assisted extraction has proven to produce the most effective antimicrobial agents. Inhibitory potential towards glucosidase, amylase, cholinesterases, and tyrosinase was evaluated in enzyme inhibition assays and molecular docking simulations. Results show that leaves of P. tenuifolia L. obtained by ultrasound-assisted extraction had the highest acetylcholinesterase and butyrylcholinesterase inhibitory activity. Namely, the complexity of the polyphenol structures, the extraction method, the used locality, and the different mechanisms of the reactions between bioactives from leaf extracts and other components (free radicals, microorganisms, and enzymes) are the main factors that influence the results of the antioxidant tests, as well as the antibacterial and enzyme-inhibitory activities of the extracts. Hydroxymethyl-phenyl pentosyl-hexoside and acetyl-hydroxyphenyl-hexoside were the first time identified in the leaf extract of the Paeonia species. Due to their proven biological activities and the confirmed existence of bioactive compounds, leaf extracts may find use in foodstuffs, functional foods, and pharmaceutical products., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Without being aware of their chemical composition, many cultures have used herbaceous peony roots for medicinal purposes. Modern phytopreparations intended for use in human therapy require specific knowledge about the chemistry of peony roots and their biological activities. In this study, ethanol-water extracts were prepared by maceration and microwave- and ultrasound-assisted extractions (MAE and UAE, respectively) in order to obtain bioactive molecules from the roots of Paeonia tenuifolia L., Paeonia peregrina Mill., and Paeonia officinalis L. wild growing in Serbia. Chemical characterization; polyphenol and flavonoid content; antioxidant, multianti-enzymatic, and antibacterial activities of extracts; and in vitro gastrointestinal digestion (GID) of hot water extracts were performed. The strongest anti-cholinesterase activity was observed in PT extracts. The highest anti-ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radical potential was observed in PP extracts, whereas against DPPH (2,2-diphenyl-1-picrylhydrazyl radicals), the best results were achieved with PO extracts. Regarding antibacterial activity, extracts were strongly potent against Bacillus cereus. A molecular docking simulation was conducted to gather insights into the binding affinity and interactions of polyphenols and other Paeonia -specific molecules in the active sites of tested enzymes. In vitro GID of Paeonia teas showed a different recovery and behavior of the individual bioactives, with an increased recovery of methyl gallate and digallate and a decreased recovery of paeoniflorin and its derivatives. PT (Gulenovci) and PP (Pirot) extracts obtained by UAE and M were more efficient in the majority of the bioactivity assays. This study represents an initial step toward the possible application of Paeonia root extracts in pharmacy, medicine, and food technologies.

Plants of the genus Prangos are intensively investigated as potential new sources of bioactive isolated products. In this work, the chemical composition of volatile constituents (essential oils and headspace volatiles) and dichloromethane extracts, as well as antimicrobial and antibiofilm activities of essential oils and MFDEs (methanol fractions of dichloromethane extracts) of Prangos trifida from Serbia, were investigated. Volatiles of roots, leaves, stems and fruits, and fatty acids and phytosterols in dichloromethane extracts of roots and fruits were analyzed by GC-FID-MS, whereas coumarins in MFDEs by LC-MS and some isolated coumarins by 1 H-NMR. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations/minimum fungicidal concentrations (MBCs/MFCs) of essential oils and MFDEs were determined against 13 microorganisms. Antibiofilm activity was assessed against four microorganisms. Additionally, congo red and ergosterol binding assays were conducted to elucidate selected mechanisms of antibiofilm action in the case of Candida albicans . Total of 52 volatile constituents, 16 fatty acids, eight phytosterols and 10 coumarins were identified. Essential oils demonstrated significant activity, surpassing that of commercial food preservatives, against six tested molds from the Aspergillus , Penicillium and Trichoderma genera, as well as against bacteria Staphylococcus aureus and Bacillus cereus . Most of the oils strongly inhibited the formation of biofilms by S. aureus, Listeria monocytogenes and Escherichia coli . MFDEs exhibited noteworthy effects against B. cereus and the tested Aspergillus species, particularly A. niger , and significantly inhibited C. albicans biofilm formation. This inhibition was linked to a marked reduction in exopolysaccharide production, while antifungal mechanisms associated with ergosterol remained unaffected.

Paeonia tenuifolia L. (steppe peony) petal extract was proficiently encapsulated into liposomes and biopolymer films in the current work, both times utilizing a single-step procedure. The encapsulation efficiency, size of the particles, and index of polydispersity (PDI), as well as the ζ potential of the obtained liposomes were determined, whereas in the case of films, the test included moisture content and mechanical property assessment. Fourier transform infrared spectroscopy (FT-IR) was used to evaluate the chemical composition and existence of numerous interactions in the systems. All the obtained encapsulates were subjected to antibacterial, antifungal and antibiofilm activity testing of the pathogens associated with human skin. The results indicated that the liposomes prepared using Phospholipon had the highest encapsulation efficiency (72.04%), making them the most favorable ones in the release study as well. The biological assays also revealed that Phospholipon was the most beneficial phospholipid mixture for the preparation of liposomes, whereas the film containing these liposomes did not have the ability to inhibit pathogen growth, making the double encapsulation of P. tenuifolia L. petal extract needless. These findings may be a first step toward the potential use of steppe peony extract-loaded films and liposomes in pharmaceutical and cosmetical industries.

In this work, a comparison between the extracts of dehydrated yerba mate ( Ilex paraguariensis ) and bio-waste of yerba mate leaves from the Brazilian industry was made. The incorporation of the functional extract as a preservative/functional ingredient in a pastry product (pancakes) was tested. The individual profile of phenolic compounds was determined by HPLC-DAD-ESI/MS, and the bioactive potential was assessed using in vitro assays for antioxidant, anti-inflammatory, antimicrobial, and cytotoxic activities. The yerba mate extracts revealed a high antimicrobial potential against the tested strains and a very promising antioxidant and anti-inflammatory action. Additionally, revealed a cytotoxic capacity for MCF-7, CaCo and AGS tumor cell-lines. In the three types of pancakes, after 3 days of storage, the chemical and nutritional characteristics remain unchanged, proving the preservative efficiency of the extract. This study showed the benefits of the use bio-waste from agro-industrial sector, focusing on sustainable production and the development of circular economy.

Paeonia peregrina Mill. is a perennial herbaceous plant species, known for the medicinal value of all of its plant parts, although the chemical composition of the petals is unknown. This study aimed to determine the chemical fingerprint of the petals and also establish the optimal extraction parameters, extraction medium, and extraction method for petals collected from different localities in Serbia. The optimization was performed in order to acquire extracts that are rich in the contents of total polyphenol content (TPC) and total flavonoid content (TFC), and also exhibit strong antioxidant activity. In addition, the influence of the extracts on several human skin pathogens was evaluated, as well as their ability to aid wound closure and act as anti-inflammatory agents. Both the extraction medium and the applied technique significantly influenced the skin-beneficial biological activities, while methanol proved to be a more favorable extraction medium. In conclusion, the extraction conditions that yielded the extract with the richest phenolic content with satisfactory biological potential varied between the assays, while the most promising locality in Serbia for the collection of P. peregrina petals was Pančevo (South Banat).

This narrative review paper provides an up-to-date overview of the potential of novel synthetic and semisynthetic compounds as antibacterials that target virulence traits in resistant strains. The review focused on research conducted in the last five years and investigated a range of compounds including azoles, indoles, thiophenes, glycopeptides, pleuromutilin derivatives, lactone derivatives, and chalcones. The emergence and spread of antibiotic-resistant bacterial strains is a growing public health concern, and new approaches are urgently needed to combat this threat. One promising approach is to target virulence factors, which are essential for bacterial survival and pathogenesis, but not for bacterial growth. By targeting virulence factors, it may be possible to reduce the severity of bacterial infections without promoting the development of resistance. We discuss the mechanisms of action of the various compounds investigated and their potential as antibacterials. The review highlights the potential of targeting virulence factors as a promising strategy to combat antibiotic resistance and suggests that further research is needed to identify new compounds and optimize their efficacy. The findings of this review suggest that novel synthetic and semisynthetic compounds that target virulence factors have great potential as antibacterials in the fight against antibiotic resistance.

Thymus comosus Heuff ex. Griseb. (Lamiaceae) is a wild thyme species endemic for Romanian Carpathian areas, frequently collected as substitute for collective herbal product Serpylli herba , cited as antibacterial and diuretic remedy in traditional medicine. The present study aimed to evaluate the in vivo diuretic effect and in vitro antimicrobial properties of three herbal preparations (infusion-TCI, tincture-TCT and an hydroethanolic extract prepared through an optimized ultrasound-assisted method-OpTC) obtained from the aerial parts of T. comosus Heuff ex. Griseb, also evaluating their comprehensive phenolic profile. In vivo diuretic effect was tested using Wistar rats treated orally with each herbal preparation (125 and 250 mg/kg dispersed in 25 ml/kg isotonic saline solution) and quantified based on cumulative urine output (ml), diuretic action and diuretic activity. Additionally, sodium and potassium excretion were monitored using a potentiometric method with selective electrodes. In vitro antibacterial and antifungal activities were assessed using p -iodonitrotetrazolium chloride assay against six bacterial strains and six fungal strains by monitoring minimum inhibitory concentration (MICs), minimum bactericidal concentrations (MBCs) and minimum fungicidal concentrations (MFCs). Finally, phenolic profile of the aforementioned herbal extracts was evaluated using an ultra-high-pressure liquid chromatography (UHPLC) coupled with high-resolution mass spectrometry (HRMS) method to check the impact of the different preparations on the most abundant and significant compounds. All the extracts exerted a mild diuretic action, TCT and OpTC inducing the most intense diuretic effect. Both herbal preparations produced a statistically significant, dose-dependent and gradual increase of the urine output, the effect being more intense at 24 h (6.63-7.13 ml/24 h). Potentiometric evaluation of urine samples collected from treated rats revealed a clear and mild natriuretic and kaliuretic effect after the administration. In terms of antimicrobial activity, E. coli (MIC-0.38 mg/ml), B. cereus (MIC-0.75 mg/ml)), Penicillium funiculosum and P. verrucosum var. cyclopium (MIC-0.19 mg/ml) showed the greater sensitivity to the tested extracts, respectively. UHPLC-HRMS screening showed that the bioactive potential of T. comosus herbal preparations was likely related to the higher amounts of phenolic acids (including rosmarinic acid), flavonoids (mainly flavones and derivatives) and other phenolics (such as different isomers of salvianolic acids) in their composition. The obtained results support the ethnopharmacological evidence regarding the mild diuretic and antibacterial potentials of the endemic wild thyme T. comosus , this study being the first one that assessed the aforementioned bioactivities for this species., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Babotă, Frumuzachi, Nicolescu, Stojković, Soković, Rocchetti, Zhang, Lucini, Crișan, Mocan and Voștinaru.)

Wild thyme aerial parts ( Serpylli herba ) are recognized as a valuable herbal product with antioxidant, anti-inflammatory, and antibacterial effects. Although pharmacopoeial regulations allow its collection exclusively from Thymus serpyllum , substitution with other species is frequent in current practice. This study analyzed the phenolic composition, antioxidant, and enzyme-inhibitory and antimicrobial activity of the hydroethanolic extracts obtained from five Romanian wild thyme species ( Thymus alpestris , T. glabrescens , T. panonicus , T. pulcherimus and T. pulegioides ). The analysis of individual phenolic constituents was performed through LC-ESI-DAD/MS 2 , while for the in vitro evaluation of antioxidant potential, TEAC, FRAP, DPPH, TBARS and OxHLIA assays were employed. The anti-enzymatic potential was tested in vitro against tyrosinase, α -glucosidase and acetylcholinesterase. High rosmarinic acid contents were quantified in all species (20.06 ± 0.32-80.49 ± 0.001 mg/g dry extract); phenolic acids derivatives (including salvianolic acids) were confirmed as the principal metabolites of T. alpestris and T. glabrescens , while eriodictyol- O -di-hexoside was found exclusively in T. alpestris . All species showed strong antioxidant potential and moderate anti-enzymatic effect against α -glucosidase and acetylcholinesterase, showing no anti-tyrosinase activity. This is the first detailed report on the chemical and biological profile of T. alpestris collected from Romanian spontaneous flora.

Spiked centaury ( Centaurium spicatum ) is a well-known medicinal plant from the Mediterranean region with various bioactivities, but there are no studies addressing the use of different solvent systems to improve its pharmacological potential. Nine extraction procedures were adapted to study the effects of solvent composition on the content of bioactive compounds in C. spicatum extracts and on corresponding bioactivities. Targeted metabolomics was performed to obtain information on the chemical composition of extracts. Ethanol-water-based extraction procedures were the most efficient in isolating polyphenols, while less polar butanol extract contained the highest amount of iridoids. Antioxidant potential analysis revealed stronger activity in extracts with higher polyphenol content. Bacillus cereus and Staphylococus aureus were designated as the most sensitive bacterial strains to the activity of extracts, while among the micromycetes tested, Penicillium funiculosum was the most susceptible strain. Butanol extract showed antivirulence potential on Candida albicans morphological transition from yeast to hyphal form, and selected extracts were effective against biofilm formation in two Candida species. All the extracts tested in this study showed no cytotoxic activity to immortalize human skin keratinocyte cell line (HaCaT), whereas extracts obtained by ethanol-water extraction stand out for their potent wound healing effects. Moreover, the influence of the extraction solvent system on various bioactivities of C. spicatum is reported herein for the first time. Overall, the results presented in this study promote the use of C. spicatum as a source of natural products with potential antioxidant, wound healing, and antimicrobial applications that are potentially safe for human use.

Flavonoids are secondary metabolites abundantly present in plants and, in most cases, essential contributors to plants bioactivity. They have been studied so far for a range of possible health-beneficial effects, including antioxidant, cardioprotective, and cytotoxic. Therefore, there are data on the antimicrobial potential of a significant number of flavonoids. However, less is known regarding their antivirulence traits. Trending antimicrobial research worldwide has pointed out the promising effects of antimicrobial strategies based on the antivirulence principle, so this review aims to present the newest research regarding the antivirulence effects of flavonoids. Articles on antivirulence flavonoids published from 2015 until now were selected. A range of molecules from this class has been studied up to date, with the most abundant data for quercetin and myricetin, while the most studied organism is Pseudomonas aeruginosa. The antivirulence attributes studied included antibiofilm assessment, followed by data on the inhibition of virulence pigments (pyocyanin, violacein, and staphyloxanthin) and virulence enzyme production (such as sortase A and elastase). Less information is collected on the inhibition of morphological transition, motility, and molecular mechanisms underlying the antivirulence properties of flavonoids and in vivo research. Flavonoids are a group of compounds with a wide range of antivirulence traits and might be further developed into essential parts of novel antimicrobial strategies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This study was designed to investigate the impact of different extraction solvent systems on the chemical composition and biological activities of Allium scorodoprasum L. (Amaryllidaceae)-the medicinal plant that was traditionally used as a remedy in the medieval period in the Balkans. Targeted chemical analysis of nine different extracts was performed by UHPLC(-)HESI-QqQ-MS/MS. Antimicrobial and antibiofilm activities of the extracts were investigated on sixteen clinical isolates of bacteria, yeasts and dermatomycetes, all isolated from infected human skin and corneal formations. Cytotoxicity and wound-healing properties were tested on human immortalized keratinocytes (HaCaT cell line). Antioxidant activity was assessed by six different assays, while beneficial potential against certain neurodegenerative diseases and type 2 diabetes was determined in selected enzyme inhibition assays coupled with molecular modeling. The results showed that the obtained extracts were rich in phenolic compounds, especially flavonoid glycosides such as rutin and kaempferol 3- O -glucoside. All of the extracts showed antimicrobial, wound-healing, antioxidant and anti-enzymatic properties. This study is the first of its kind, linking the medieval medicinal use of wild-growing flowers of A. scorodoprasum with contemporary in vitro scientific approaches.

Hypericum perforatum L., also known as St. John’s Wort, is recognized worldwide as a valuable medicinal herb; however, other Hypericum species were intensively studied for their bioactive potential. To fill the research gap that exists in the scientific literature, a comparative evaluation between H. alpigenum Kit., H. perforatum L. and H. rochelii Griseb. & Schenk was conducted in the present study. Two types of herbal preparations obtained from the aerial parts of these species were analyzed: extracts obtained through maceration and extracts obtained through magnetic-stirring-assisted extraction. LC-DAD-ESI-MSn analysis revealed the presence of phenolic acids, flavan-3-ols and flavonoid derivatives as the main constituents of the above-mentioned species. Moreover, all extracts were tested for their antioxidant, enzyme-inhibitory and antimicrobial potential. Our work emphasizes for the first time a detailed description of H. rochelii phenolic fractions, including their phytochemical and bioactive characterization. In comparison with the other two studied species, H. rochelii was found as a rich source of phenolic acids and myricetin derivatives, showing important antioxidant, anticholinesterase and antibacterial activity. The study offers new perspectives regarding the chemical and bioactive profile of the less-studied species H. alpigenum and H. rochelii.

Hesperetin is the aglycone of citrus flavonoid hesperidin. Due to the limited information regarding hesperetin antimicrobial potential and emerging need for novel antimicrobials, we have studied its antimicrobial activity (microdilution assay), antibiofilm activity with different assays in two models (mono- and polymicrobial biofilm), and toxicity (MTT and brine shrimp lethality assays). Hesperetin inhibited growth of all Candida isolates (minimal inhibitory concentration, MIC, 0.165 mg/mL), while it’s inhibitory potential towards Staphylococcus aureus was lower (MIC 4 mg/mL). Hesperetin (0.165 mg/mL) reduced ability of Candida to form biofilms and moderately reduced exopolysaccharide levels in biofilm matrix. Effect on the eradication of 24 h old C. albicans biofilms was promising at 1.320 mg/mL. Inhibition of staphylococcal biofilm formation required higher concentrations of hesperetin (<50% inhibition with MIC 4 mg/mL). Establishment of polymicrobial C. albicans-S. aureus biofilm was significantly inhibited with the lowest examined hesperetin concentration (1 mg/mL) in crystal violet and CFU assays. Hesperetin toxicity was examined towards MRC-5 fibroblasts (IC50 0.340 mg/mL) and in brine shrimp lethality assay (LC50 > 1 mg/mL). Hesperetin is efficient in combating growth and biofilm formation of Candida species. However, its antibacterial application should be further examined due to the cytotoxic effects provoked in the antibacterial concentrations.

Pineapple is a tropical fruit consumed fresh or processed into various food products. However, the peel and crown of this fruit are not industrially exploited, thus generating tons of by-products that represent an economic and environmental concern. In order to promote the upcycling of these by-products, this work aimed to characterize the phenolic profile of its hydroethanolic extracts obtained from pineapple peel and crown leaves and to evaluate their in vitro bioactivity. The HPLC-DAD-ESI/MS analysis allowed the identification of 25 phenolic compounds, including phenolic acids and flavonoids. The antioxidant, cytotoxic, and antimicrobial activity assays highlighted the peel extract as the most promising and, therefore, it was incorporated into a traditional Portuguese pastry cake as a functional ingredient. The nutritional parameters of the developed food were not affected by the incorporation of the extract, but it promoted the antioxidant activity during its shelf-life. Overall, pineapple peel and crown appeared as promising by-products to be exploited by the food industry, which can be achieved through a circular economy approach.

Several scientific studies have been proving the bioactive effects of many aromatic and medicinal plants associated with the presence of a high number of bioactive compounds, namely phenolic compounds. The antioxidant, anti-inflammatory, and antimicrobial capacities of these molecules have aroused high interest in some industrial sectors, including food, pharmaceuticals, and cosmetics. This work aimed to determine the phenolic profiles of the infusions and hydroethanolic extracts of five plants ( Carpobrotus edulis , Genista tridentata , Verbascum sinuatum , Cytisus multiflorus , and Calluna vulgaris ) that have been employed in many traditional preparations. In addition, the antioxidant, antimicrobial, anti-inflammatory, and anti-tumoral activity of each different preparation was evaluated using in vitro assays. The HPLC-DAD-ESI/MS profile revealed the presence of eighty phenolic compounds, belonging to seven different families of compounds. Regarding antioxidant properties, the hydroethanolic extract of C. edulis showed a potent effect in the TBARS assay (IC 50 = 1.20 µg/mL), while G. tridentata hydroethanolic extract achieved better results in the OxHLIA test (IC 50 = 76 µg/mL). For cytotoxic and anti-inflammatory results, V. sinuatum infusions stood out significantly, with GI 50 = 59.1-92.1 µg/mL and IC 50 = 121.1 µg/mL, respectively. Finally, C. edulis hydroethanolic extract displayed the most relevant antibacterial activity, showing MBC values of 0.25-1 mg/mL, while G. tridentata hydroethanolic extract exerted the greatest antifungal effects (MFC of 0.5-1 mg/mL). The results of this study deepen the knowledge of the phenolic profiles and also provide evidence on the bioactive properties of the species selected, which could be considered highly valuable options for research and application in several sectors, namely food, cosmetics, and pharmaceuticals.

The cosmetic industry is constantly searching for bioactive ingredients, namely, those obtained from natural sources with environmentally friendly connotations and less toxic effects. A previous study of our research group optimized the extraction of phenolic compounds from Juglans regia by heat-assisted extraction. Due to its richness in different phenolic compounds, the present work aimed to develop a formulation containing J. regia leaf extract. The extract's antioxidant, anti-tyrosinase, antimicrobial, anti-inflammatory, wound healing, cytotoxicity, and photostability properties were evaluated. The extract was then incorporated into an O/W base cream, followed by characterization of the final formulation in terms of its antioxidant properties, phenolic composition, and stability over time and at different storage conditions. The most abundant compounds in the hydroethanolic extract were 3- O -caffeoylquinic acid (18.30 ± 0.04 mg/g), quercetin- O -pentoside (9.64 ± 0.06 mg/g), and quercetin 3- O -glucoside (6.70 ± 0.19 mg/g). Besides those, the extract presented antioxidant, anti-inflammatory, wound closure, and antibacterial effects against several skin pathogens. In addition, HaCaT cell viability was maintained up to 98% at 400 µg/mL. Within Proteus vulgaris -infected HaCaT cells, the extract also presented an over 40% bacterial mortality rate at its nontoxic concentration (200 µg/mL). After incorporating the extract, the obtained formulation presented a good physicochemical profile over time and at different storage conditions while also maintaining its antioxidant effect; as such, it can be considered stable for topical application. Future work to evaluate its performance in terms of skin permeation and detailed toxicological studies with a focus on regulatory requirements, involving skin irritation, eye irritation, genotoxicity, photo-irritation, and dermal absorption, should be conducted, as the prepared formulation demonstrated relevant properties that deserve to be further explored.

The rising incidence of antibiotic resistant microorganisms urges novel antimicrobials development with polyphenols as appealing potential therapeutics. We aimed to reveal the most promising polyphenols among hesperetin, hesperidin, naringenin, naringin, taxifolin, rutin, isoquercitrin, morin, chlorogenic acid, ferulic acid, p -coumaric acid, and gallic acid based on antimicrobial capacity, antibiofilm potential, and lack of cytotoxicity towards HaCaT, and to further test its antivirulence mechanisms. Although the majority of studied polyphenols were able to inhibit bacterial growth and biofilm formation, the most promising activities were observed for rutin. Further investigation proved rutin's ability to prevent/eradicate Pseudomonas aeruginosa and MRSA urinary catheter biofilms. Besides reduction of biofilm biomass, rutin antibiofilm mechanisms included reduction of cell viability, exopolysaccharide, and extracellular DNA levels. Moderate reduction of bacterial adhesion to human keratinocytes upon treatment was observed. Rutin antivirulence mechanisms included an impact on P. aeruginosa protease, pyocyanin, rhamnolipid, and elastase production and the downregulation of the lasI , lasR , rhlI , rhlR , pqsA and mvfR genes. Rutin also interfered with membrane permeability. Polyphenols could repress antibiotic resistant bacteria. Rutin has shown wide antimicrobial and antibiofilm capacity employing a range of mechanisms that might be used for the development of novel antimicrobials.

Despite abundant research in the field of antifungal drug discovery, fungal infections remain a significant healthcare burden. There is an emerging need for the development of novel antifungals since those currently available are limited and do not completely provide safe and secure protection. Since the current knowledge regarding the physiology of fungal cells and the infection mechanisms is greater than ever, we have the opportunity to use this for the development of novel generations of antifungals. In this review, we selected and summarized recent studies describing agents employing different antifungal mechanisms. These mechanisms include interference with fungal resistance, including impact on the efflux pumps and heat shock protein 90. Additionally, interference with virulence factors, such as biofilms and hyphae; the impact on fungal enzymes, metabolism, mitochondria, and cell wall; and antifungal vaccines are explored. The agents investigated belong to different classes of natural or synthetic molecules with significant attention given also to plant extracts. The efficacy of these antifungals has been studied mainly in vitro with some in vivo, and clinical studies are needed. Nevertheless, there is a large quantity of products employing novel antifungal mechanisms that can be further explored for the development of new generation of antifungals.

This study was designed to explore functional food properties of edible seed oil obtained from Tamjanika seeds-autochthonous grape variety of Balkan Peninsula. In order to accomplish our goals, seed oil was isolated by Soxhlet apparatus and chemically characterized regarding fatty acids, carotenoids, tocopherols, and tocotrienols. Antimicrobial activity of the isolated oil was tested by microdilution method. For that purposes, six bacterial species were used, belonging to human infectious agents and food contaminants. Furthermore, the activity of the oil was investigated against clinical isolates of dermatomycetes. Our study has shown that oil of Vitis vinifera L. Tamjanika variety was an abundant source of polyunsaturated fatty acids (81.43%) with predominant linoleic acid. HPLC analysis revealed the presence of carotenoid lutein (0.15 mg/100 g). The seed oil was rich in tocotrienols (85.04 mg/100 g) predominating over tocopherols (8.37 mg/100 g). The oil possessed microbicidal activity against all the tested microbes. Bacteria were more sensitive to the effect of the oil (minimum inhibitory concentration [MIC] 7.7-15.4) when compared with oil effect on tested dermatomycetes (MIC 20-40). Our investigation has shown for the first time that grape oil could be active against wide spectrum of bacteria and clinically isolated dermatomycetes. The significance of this study lies in the fact that it pointed out the functional food properties of grape seed oil that was fully chemically characterized., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Five new complexes of the palladium(II) ion (C1-C5) having the general formula [(PdL 2 )]Cl 2 with some 2-aminothiazoles (L1-L5), where L1 = 2-amino-4-(3,4-difluorophenyl)thiazole, L2 = 2-amino-5-methyl-4-phenylthiazole, L3 = 2-amino-4-phenylthiazole, L4 = 2-amino-4-(4-chlorophenyl)thiazole, and L5 = 2-amino-4-(2,4-difluorophenyl)thiazole, have been synthesized and characterized by elemental microanalysis and infrared, 1 H NMR and 13 C NMR spectroscopy. The in vitro antimicrobial activity of the five ligands and the corresponding Pd(II) complexes is investigated. Testing is performed by the microdilution method and the minimum inhibitory concentration (MIC) and minimum microbicidal concentration (MMC) have been determined. Testing is conducted against 11 microorganisms (nine strains of pathogenic bacteria and two yeast species). The tested ligands and palladium(II) complexes show selective, high and moderate activity. There is a difference in antimicrobial activity between the ligands and the corresponding palladium(II) complexes. The complexes have significant anti-staphylococcal activity and activity on Pseudomonas aeruginosa which is better than the positive control. The interactions of newly synthesized palladium(II) complexes with calf thymus DNA (CT-DNA) were investigated using UV-Vis absorption and fluorescence spectroscopy. Analysis of UV-absorption and fluorescence spectra indicates the formation of a complex between the palladium(II) complexes and DNA. The high values of intrinsic binding constants, K b , of the order 10 4 M -1 and Stern-Volmer quenching constants, K SV , of the order 10 5 M -1 indicated very good binding of all complexes to CT-DNA. Also, the new Pd(II) complexes show high cytotoxic activity towards the human prostate cancer cell line and insignificant activity towards non-cancerous human fibroblasts. Future research could additionally explore the biological activity of Pd(II) complexes presented in this paper and investigate the possibility of their implementation in clinical practice.

Seseli L. is one of the largest genera of the Apiaceae family widely known for their traditional uses as herbal remedies. In the present study, the methanolic and water extracts of two Seseli species, S. gummiferum and S. transcaucasicum were evaluated for their bioactive contents and biological activities. The total phenolic and flavonoid contents in the extracts ranged from 19.09 to 24.33 mg GAE/g and from 0.45 to10.09 mg RE/g, respectively. Moreover, while narcissin was detected as the most abundant component in the methanolic extract of S. transcaucasicum (261.40 µg/g), chlorogenic acid was identified as the major component in all the other extracts, although a high amount was also present in the methanolic S. transcaucasicum extract (107.48-243.12 µg/g). The total antioxidant capacity was also determined by the phosphomolybdenum assay (0.66-1.18 mM TE/g). Other antioxidant assays such as the radical scavenging assays (DPPH: 5.51-11.45 mg TE/g; ABTS: 43.46-51.91 mg TE/g), reducing assays (CUPRAC: 41.67-53.20 mg TE/g; FRAP: 31.26-34.14 mg TE/g), as well as the metal chelating activity assay (14.38-38.57 mg EDTAE/g) were conducted. All the extracts showed inhibitory potential against the enzyme's amylase (0.12-0.78 mM ACAE/g), acetyl- and butyryl-cholinesterase (0.15-9.71 mg GALAE/g), while only the methanolic extracts acted as inhibitors of tyrosinase (107.15 and 109.37 mg KAE/g) and only the water extract of S. gummiferum displayed anti-glucosidase activity (0.13 mM ACAE/g). Interestingly, the methanolic extracts of both Seseli species showed lower cytotoxicity towards HaCaT cells (IC 50 : >500 µg/mL), compared to the water extracts (IC 50 : 267.8 and 321.41 µg/mL). Besides, only the methanolic extracts showed a slight wound healing effect (28.21 and 31.23%). All extracts showed antibacterial action against Staphylococcus lugdunensis (minimum inhibitory and bactericidal concentrations: 0.025-2 mg/mL). S. gummiferum methanolic extract, which exhibited the highest antibacterial potency was found to inhibit adhesion and invasion of S. lugdunensis to HaCaT cells as well. Taken together, this study demonstrated the two Seseli species to harbour interesting bioactive components, in particular polyphenolics and to exhibit several biological properties that could be further investigated for their potential exploitation as healing agents as supported by various traditional medicinal uses.

Chicory ( Cichorium intybus L.) is an important industrial crop cultivated mainly to extract the dietary fiber inulin. However, chicory also contains bioactive compounds such as sesquiterpene lactones and certain polyphenols, which are currently discarded as waste. Plants are an important source of active pharmaceutical ingredients, including novel antimicrobials that are urgently needed due to the global spread of drug-resistant bacteria and fungi. Here, we tested different extracts of chicory for a range of bioactivities, including antimicrobial, antifungal and cytotoxicity assays. Antibacterial and antifungal activities were generally more potent in ethyl acetate extracts compared to water extracts, whereas supercritical fluid extracts showed the broadest range of bioactivities in our assays. Remarkably, the chicory supercritical fluid extract and a purified fraction thereof inhibited both methicillin-resistant Staphylococcus aureus (MRSA) and ampicillin-resistant Pseudomonas aeruginosa IBRS P001. Chicory extracts also showed higher antibiofilm activity against the yeast Candida albicans than standard sesquiterpene lactone compounds. The cytotoxicity of the extracts was generally low. Our results may thus lead to the development of novel antibacterial and antifungal preparations that are both effective and safe for human use.

Artemisia absinthium L. (Asteraceae) is traditionally used for gastrointestinal ailments and disorders linked to numerous risk factors including microbial infections. We aimed to provide contemporary evidence for its ethnopharmacological use and determine its antimicrobial capacity and mode of action, cytotoxicity, and phenolic constituents. Ethnopharmacological survey was conducted using semistructured interviews. Antimicrobial and antibiofilm capacities were determined by microdilution/crystal violet assay, respectively. Modes of action tested include estimation of exopolysaccharide production (congo red binding assay) and interference with membrane integrity (crystal violet uptake and nucleotide leakage assay). Cytotoxicity was determined using crystal violet assay. Polyphenolic profiling was done by advanced liquid chromatography/mass spectrometry (UHPLC-LTQ OrbiTrap MS). Artemisia absinthium in Serbia is traditionally used for gastrointestinal disorders, among others. Further study revealed high antifungal capacity of herb ethanolic extract towards range of Candida species (MIC 0.5-1 mg/mL) along with promising antibacterial activities (MIC 0.25-4 mg/mL). Interference with membrane integrity could be observed as a possible antimicrobial mechanism. Antibiofilm potential can be considered as high (towards C. krusei ) to limited (towards P. aeruginosa ) and moderate based on reduction in exopolysaccharide content. In concentrations up to 400  µ g/mL, no cytotoxicity was observed towards HaCaT and HGF-1 cell lines. Polyphenolic analysis revealed twenty-one different constituents. A. absinthium usage as a gastrointestinal ailment remedy has been confirmed in vitro by its antimicrobial capacity towards microorganisms whose presence is linked to the diseases and associated complications and noncytotoxic nature of the natural product. The observed activities could be attributed to the present phenolic compounds., Competing Interests: The authors declare that they have no conflicts of interest regarding the publication of this paper., (Copyright © 2021 Marija Ivanov et al.)

Given the importance of colour in the general acceptance or rejection of a product, the use of colorants is a widespread practice, particularly in the food industry. At the same time, with the increasing consumers' awareness of the health effects that some artificial colorants can exert, there is a growing tendency to prioritize foodstuffs containing natural additives. In this work, Morus nigra L. and Rubus fruticosus L. fruit juices were characterized in terms of anthocyanins, organic acids, free sugars, and tocopherols, as also regarding their bioactive properties. Given their richness in anthocyanins, this study also aimed to prepare different solid colouring formulations by the spray-drying technique, using as stabilizers maltodextrin and arabic gum. Six free sugars and two organic acids were detected in the fruit juices, as well as the four tocopherol isoforms. Two cyanidin derivatives were found in M. nigra (cyanidin-3- O -glucoside and cyanidin- O -rhamnoside) and other four in R. fruticosus (cyanidin- O -hexoside, cyanidin-3- O -glucoside, cyanidin- O -pentoside, and cyanidin-3- O -dioxaloilglucoside). The developed colouring formulations revealed a good stability over time, in terms of anthocyanin concentration and colour parameters, and revealed to be safe for consumption, either concerning their low microbial load and lack of cytotoxicity. Thus, they represent a promising natural alternative to the massively used artificial colorants.

This study aims to fill the gaps in ethnomycological knowledge in Serbia by identifying various fungal species that have been used due to their medicinal or nutritional properties. Ethnomycological information was gathered using semi-structured interviews with participants from different mycological associations in Serbia. A total of 62 participants were involved in this study. Eighty-five species belonging to 28 families were identified. All of the reported fungal species were pointed out as edible, and only 15 of them were declared as medicinal. The family Boletaceae was represented by the highest number of species, followed by Russulaceae, Agaricaceae and Polyporaceae. We also performed detailed analysis of the literature in order to provide scientific evidence for the recorded medicinal use of fungi in Serbia. The male participants reported a higher level of ethnomycological knowledge compared to women, whereas the highest number of used fungi species was mentioned by participants within the age group of 61-80 years. In addition to preserving ethnomycological knowledge in Serbia, this study can present a good starting point for further pharmacological investigations of fungi.

Food poisoning is a common cause of illness and death in developing countries. Essential oils (EOs) could be effective and safe natural preservatives to prevent and control bacterial contamination of foods. However, their high sensitivity and strong flavor limit their application and biological effectiveness. The aim of this study was firstly the chemical analysis and the antimicrobial evaluation of the EOs of Origanum onites L. and Satureja thymbra L. obtained from Symi island (Greece), and, secondly, the formulation of propylene glycol-nanovesicles loaded with these EOs to improve their antimicrobial properties. The EOs were analyzed by GC-MS and their chemical contents are presented herein. Different nanovesicles were formulated with small average sizes, high homogeneity, and optimal ζ-potential. Microscopic observation confirmed their small and spherical shape. Antibacterial and antifungal activities of the formulated EOs were evaluated against food-borne pathogens and spoilage microorganisms compared to pure EOs. Propylene glycol-nanovesicles loaded with O. onites EO were found to be the most active formulation against all tested strains. Additionally, in vitro studies on the HaCaT cell line showed that nanovesicles encapsulated with EOs had no toxic effect. The present study revealed that both EOs can be used as alternative sanitizers and preservatives in the food industry, and that their formulation in nanovesicles can provide a suitable approach as food-grade delivery system.

Structural diversity of biologically active compounds identified in plants after many years of storage is rarely reported in literature. Herein, we studied chemical profile and biological activities of Phlomis fruticosa L. after plant material storage for 20 years. Chemical analyzes were performed by UHPLC-LTQ-Orbitrap/MS, and revealed presence of 44 compounds: including 13 phenolic acids, 9 phenylethanoids, 20 flavonoids and 2 phenolic related compounds (a phenolic acid derivative and an aliphatic alcohol). The extract showed antimicrobial activity, being the most potent against Aspergillus fumigatus with minimum inhibitory concentration of 0.31 mg/mL. Also, the extract was able to inhibit biofilm formed by Candida species and to inhibit biofilm formation by Staphylococcus aureus. Obtained results revealed that the extract has potential to interfere with the cell membrane permeability of Candida albicans and to suppress production of virulence factor staphyloxanthin in S. aureus. Furthermore, the extract inhibited the activity of α-amylase which is one of the therapeutic targets for diabetes type II. Also, the antiproliferative effect of the extract was demonstrated on human cancer cell lines, while the extract did not exhibit any cytotoxic effect on primary human cells. Based on the obtained results, P. fruticosa could be an interesting source of biologically active compounds even after long term storage., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Anthriscus cerefolium (L.) Hoffm. is a plant traditionally used around the globe since antiquity. Although widely used in many traditional medicines in different cultures, from the scientific point of view it is poorly investigated. Glioblastoma, a tumor type with poor prognosis, is the most common and lethal brain tumor in adults. Current therapeutic strategies for glioblastoma include surgery, radiation and chemotherapy. On the other hand, it has been revealed that patients with cancers are highly susceptible to microbial infections due to the invasive nature of cancer treatment approaches. This study was designed to investigate the chemical profile of herba Anthriscii cerefoli methanolic extract by applying UHPLC-LTQ OrbiTrap MS 4 analysis and to analyze its anti-glioblastoma and antimicrobial activities. This study revealed that methanolic extract of herba Anthrisc cerefolii contained phenolic acids and flavonoids, with 32 compounds being identified. Anti-glioblastoma activity was investigated in vitro using A172 glioblastoma cell line. The cytotoxic effects of the extract on A172 cells were compared to the same effect on primary human gingival fibroblast (HGF-1) cells. Decreased rate of proliferation and changes in cell morphology were detected upon treatment of A172 cells with the extract. The antimicrobial activity of extract was tested against Staphylococcus aureus and Candida species. The extract was active against the tested bacterium and yeasts, inhibiting free floating cells and microbial biofilms. This study is the first one to provide a detailed description of the chemical profile of A. cerefolium extract dealing with scientific insights into its anti-glioblastoma and antimicrobial activities.

The ingestion of bioactive compounds has revealed health benefits, namely in the prevention and/or treatment of several diseases. This work aims to characterize the phenolic profile of three colour varieties of Chenopodium quinoa Willd. grains (black, red and white), and also evaluate their cytotoxic and antimicrobial activity. All varieties revealed the presence of phenolic compounds, namely, quercetin and kaempferol derivatives. In this study, quinoa grains did not reveal any anti-proliferative capacity in tumour cell lines, and, as expected, they were devoid of any toxicity. All of the analysed extracts possessed antibacterial and antifungal activities (inhibitory and bactericidal/fungicidal) against the microbial strains considered, exhibiting promising values of minimum bactericidal concentrations (mean MBC 0.153-0.916 mg/mL) and minimum fungicidal concentrations (mean MFC 0.211-0.884 mg/mL). Quinoa varieties represent a good source of bioactive compounds, interfering beneficially in the organism, specifically as antimicrobial agents. Thus, these extracts could be used in the development of bioactive ingredients., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

This study explored the chemical profile of the aerial parts of Ononis spinosa and further investigated its biological activities. Chemical profiling of the extract revealed the presence of 63 different compounds: phenolic acids, flavonoid glycosides and aglycones, isoflavonoid glycosides and aglycones, and other related compounds. Our results revealed that the extract was active against 8 strains of free floating bacteria. It showed anti-biofilm potential against Staphylococcus aureus and was able to supress the production of staphyloxanthin in S. aureus at sub-minimal inhibitory concentrations. Its antioxidant activity was evaluated by using several assays (phosphomolybdenum, DPPH, ABTS, CUPRAC, FRAP, and metal chelating assay), which showed that the extract exhibited a dose dependent activity. Inhibition of AChE, BChE, amylase, glucosidase and tyrosinase was achieved by the extract, demonstrating its anti-enzymatic activity. The antiproliferative potential of the extract towards human cancer cell lines (HepG2, MCF-7, SiHa and A172) was determined by using the crystal violet assay. Ki67, a marker of proliferation was downregulated in the A172 glioblastoma cell line.

The potential of passion fruit ( Passiflora edulis Sims) epicarp to produce anthocyanin-based colorants with bioactive properties was evaluated. First, a five-level three-factor factorial design coupled with response surface methodology was implemented to optimize the extraction of anthocyanins from dark purple epicarps. The extraction yield and cyanidin-3- O -glucoside content were used as response criteria. The constructed models were fitted to the experimental data and used to calculate the optimal processing conditions ( t = 38 min, T = 20 °C, S = 0% ethanol/water ( v/v ) acidified with citric acid to pH 3, and R S/L = 50 g/L) that lead to maximum responses (3.4 mg/g dried epicarp and 9 mg/g extract). Then, the antioxidant, antimicrobial, and cytotoxic activities of anthocyanin extracts obtained using the optimized method and a conventional extraction method were evaluated in vitro. The extract obtained by the optimized method revealed a higher bioactivity, in agreement with the higher cyanidin-3- O -glucoside content. This study highlighted the coloring and bioactive potential of a bio-based ingredient recycled from a bio-waste, which promotes a sustainable bioeconomy in the agri-food sector.

Balkan Peninsula is one of the most important biodiversity centers in Europe. Despite that, the usage of plant species in the traditional medicine of some Balkan regions remained largely unexplored in the past. This study aimed to collect and document data on the traditional use of medicinal plants in Pčinja district in South-Eastern Serbia, which is among the least developed regions in Serbia. Also, comparison with data collected by Dr. Jovan Tucakov, in a book called Herbal therapy was conducted. The survey was carried out using semi-structured interviews and 113 informants were interviewed. Quantitative ethnobotany factors were calculated, allowing us discussing the results. The informants reported data on 86 medicinal plants belonging to 43 families in Pčinja district. Lamiaceae, Asteraceae , and Rosaceae were the dominant locally used families. The species with the highest number of use reports were Mentha piperita , Matricaria chamomilla , and Hypericum perforatum . Gastrointestinal ailments, respiratory problems and skin diseases were the most frequently reported indications. Usually, the administration was primarily oral followed by topical applications. Leaves were dominantly exploited plant parts and the most frequent preparation form was infusion. Medicinal plants in Pčinja district are mainly used as a mode of primary health care for treating minor health issues. After comparing our results with the ones collected half a century ago by Dr. Jovan Tucakov we can conclude that plant species mentioned in our investigation previously had a much wider spectrum of application., (Copyright © 2020 Živković, Ilić, Šavikin, Zdunić, Ilić and Stojković.)

Fungi are known to modify the properties of lignocellulosic materials during solid-state fermentation (SSF). In this study, agricultural side-streams (sunflower seed hulls, rice husks and rice straw) were used as substrates for SSF with dikaryotic and monokaryotic strains of Pleurotus sapidus. The phenolic profiles of the mentioned substrates were characterized by LC-DAD/ESI-MS n pre- and post- fermentation. Moreover, antioxidant, cytotoxic and antimicrobial activities were screened against oxidizable cellular substrates, tumour and primary cell lines, and different bacteria and fungi, respectively. The concentration of phenolic compounds in the crop side-streams was reduced after fermentation with both strains of the fungus. The fermented extracts also displayed lower antioxidant and cytotoxic activities and had no hepatotoxicity. The antimicrobial activity depended upon the crop side-stream and/or SSF conditions. These results indicate that P. sapidus represent a good candidate to modify the phenolic fraction presents in crop side-streams with a consequent decrease in its bioactivities. However, the SSF with P. sapidus strains play an interesting role in the detoxification of plant materials which can be used for different applications according to the "reduce - reuse - recycle" concept contributing with the sustainable land use and circular economy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Although the nutritional profile, bioactivities, and uses of mesquite pod flour from various Prosopis species have been studied, limited research has been conducted on Prosopis pallida (Humb, & Bonpl. Ex Willd.) Kunth mesquite flour. This study aimed to characterize the nutritional quality and bioactive properties of P. pallida pod flour and to assess its technological performance in breadmaking as a partial replacer of white wheat flour. Peruvian P. pallida mesquite flour was found to have an appealing nutritional profile, with high contents of dietary fiber (29.6% dw) and protein (9.5% dw), and low contents of fat (1.0% dw) and carbohydrates (57.6% dw). It is a source of palmitic (12.6%), oleic (35.5%), and linoleic acids (45.8%), α-, β-, and γ- tocopherols, and contains phenolic compounds such as apigenin glycoside derivatives with proven antioxidant capacities. Extracts of P. pallida flour were also found to have antimicrobial and antifungal effects and did not show hepatoxicity. When formulated as a wheat flour replacer, increasing mesquite flour levels yield composite doughs of lower stickiness and extensibility, and composite breads of lower elasticity ( p < 0.01). However, up to a level of 10%, mesquite flour significantly increases loaf volume, reduces crumb hardness, and produces a more uniform crumb of small size alveoli ( p < 0.01). Considering the purpose of improving the nutritional and technological quality of wheat flour bread, the addition of P. pallida pod flour can be highly recommended.

Several plants have been used for medicinal applications and have been traditionally consumed as decoctions and infusions. Although some herbs are used alone as a beverage, they are often blended in mixtures to maximize their effects. Herein, the nutritional characterization of six infusions from herbal blends was evaluated using the official methods of analysis (AOAC international). A further characterization of the individual phenolic profile was also performed by HPLC-DAD/ESI-MSn, and finally bioactive potential was determined by evaluating the antioxidant, cytotoxic, anti-inflammatory, and antimicrobial activities of each blend. The wide variety of plants in each sample led to variability in the results for all analyzed parameters. However, blends containing 15% Laurus nobilis L. and 15% Juglan regia L. in their composition showed higher sugar content and energy contribution; higher concentration of phenolic compounds (phenolic acids and flavonoids); greater antioxidant, cytotoxic, and anti-inflammatory capacity; and also better antimicrobial effects against all the tested bacterial and fungal strains. Further studies will be necessary to evaluate the real synergistic effects that these two species show in the presence of other plants, and to evaluate their potential for application in various food, pharmaceutical, and nutraceutical products as infusion preparations.

Ononis spinosa L. is a plant traditionally used as folk remedy. There are numerous studies regarding chemical constituents and health beneficial properties of Ononidis Radix. The following study was designed to investigate chemical composition and antifungal potential of the methanolic extract obtained from the O. spinosa L. herb. Chemical analyses regarding phenolic compounds of O. spinosa were performed by liquid chromatography with mass spectrometry (LC-DAD-ESI/MSn). Antifungal activity, antibiofilm properties and antifungal mode of action of the extract were evaluated, as well as cytotoxicity. Chemical analyses revealed the presence of flavonoids, isoflavonoids and phenolic acids in O. spinosa, with kaempherol- O -hexoside-pentoside being the most abundant compound (5.1 mg/g extract). Methanolic extract was active against all of the tested microfungi with Penicillium aurantiogriseum being the most sensitive to the extract inhibitory effect at 0.02 mg/mL; and effectively inhibited biofilms formed by Candida strains. Minimum fungicidal concentrations of extract rose in the presence of ergosterol and leakage of cellular components was detected. The extract showed no cytotoxicity to human gingival fibroblast (HGF-1) cells. This study significantly contributes to overall knowledge about medicinal potential of O. spinosa herbal extract and enlightens previously unrevealed properties. O. spinosa aerial parts seem to be an interesting candidate for the development of antifungal preparations, non-toxic to human cells.

Cardoon is a multi-purpose crop for several industries. In this study, cardoon seeds were separated according to the viability and characterized for their chemical composition and bioactivities. Viable seeds contained higher levels of α-tocopherol (6.7 mg/100 g), lipids (23.11 g/100 g, manly oleic and linoleic acids), and free sugars (5.4 g/100 g) than the unviable ones. The hydroethanolic extract of viable seeds presented a higher concentration of phenolic compounds, namely 5-O-caffeoylquinic (8.0 mg/g) and 3,5-O-dicaffeoylquinic (43.9 mg/g) acids, and greater in vitro antioxidant activity. Both extracts showed antibacterial properties, but the best results were achieved with unviable seeds. The extracts had similar antifungal activity but did not reveal anti-inflammatory capacity or cytotoxicity to the tested cell lines. Therefore, while viable seeds contained antioxidant phytochemicals and an energy and carbon source for germination, unavailable seeds stood out for their potential to be used in the development of bio-based antibacterial ingredients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The following review is oriented towards microbes linked to Alzheimer's disease (AD) and antimicrobial effect of compounds and extracts derived from aquatic organisms against specific bacteria, fungi and viruses which were found previously in patients suffering from AD. Major group of microbes linked to AD include bacteria: Chlamydia pneumoniae, Helicobacter pylori, Porphyromonas gingivalis, Fusobacterium nucleatum, Prevotella intermedia, Actinomyces naeslundii, spirochete group; fungi: Candida sp., Cryptococcus sp., Saccharomyces sp., Malassezia sp., Botrytis sp., and viruses: herpes simplex virus type 1 (HSV-1), Human cytomegalovirus (CMV), hepatitis C virus (HCV). In the light of that fact, this review is the first to link antimicrobial potential of aquatic organisms against these sorts of microbes. This literature review might serve as a starting platform to develop novel supportive therapy for patients suffering from AD and to possibly prevent escalation of the disease in patients already having high-risk factors for AD occurrence., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Heavy metals are elements that are naturally found in the earth. They are used in many modern-day applications in agriculture, medicine, and industry. Heavy metal poisoning occurs when the body's soft tissues absorb too much of a particular metal. The heavy metals of interest for this review paper were cadmium, arsenic, mercury, and lead since these are the most common metals that the human body can absorb in toxic amounts. Different plant species were investigated in recent years for their effect on oxidative stress parameters after intoxication with heavy metals., Objectives: This review paper is focused on the current update to research on heavy metals induced oxidative stress in animal models and improvement of the oxidative stress parameters upon/co-/after treatment with different plant extracts and isolated compounds., Methods: The available literature was screened for the novel data regarding the influence of plant extracts and compounds on heavy metals induced oxidative stress. For that purposes Scopus database was used, looking for the publications in the last 5-10 years with the key terms: plant extracts, oxidative stress, in vivo, cadmium, lead, mercury and arcenic., Results: Various parameters of oxidative stress were investigated, and their improvement with plant extracts/ compounds was observed in the brain, lungs, kidneys, liver, uterus, testis, thymus, spleen, heart, skin and blood of experimental animals. Common parameters used to determine oxidative stress in animals were: superoxide dismutase; catalase; reduced glutathione; glutathione reductase; glutathione-S-transferase; glutathione peroxidase; lipid peroxidation; oxidized glutathione; malondialdehyde; xanthine oxidase; nonprotein-soluble thiol; thioredoxin reductase; total sulphydryl group; nitric oxide; γ-glutamyl cysteine synthetase., Conclusion: The most investigated species for antioxidant effects upon intoxication with heavy metals seem to be Allium sp., Bacopa monniera, Camellia sinensis, Moringa oleifera, Vitis vinifera and Zingiber officinale. According to literature data, the most promising effect to alleviate symptoms of intoxication was achieved with proanthocyanidins obtained from Vitis vinifera., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)