Search Results (702)

Blackcurrant (Ribes nigrum L.) fruits and their by-products represent valuable sources of bioactive compounds. This study compared fruits, juice, seeds, oil, and leaves with respect to their content of selected bioactive components, potential intestinal availability of polyphenols estimated by dialysis, and in vitro biological activities. Blackcurrant leaves contained several-fold higher levels of polyphenols in the dialyzable fraction (651.3 mg/100 g) than fruits (255.1 mg/100 g) and juice (261.4 mg/100 g). Seeds exhibited the strongest antioxidant activity among all matrices, reaching 13.3, 10.9 and 11.4 mmol Trolox/100 g in the ABTS, FRAP and ORAC assays, respectively. Hydrophilic fractions of juice and seeds showed notably stronger α-amylase inhibition (IC₅₀ < 0.01 mg/mL) than the antidiabetic drug acarbose (IC₅₀ = 0.35 mg/mL). Juice also demonstrated higher pancreatic lipase inhibition (IC₅₀ = 0.01 mg/mL) compared with Orlistat (IC₅₀ = 0.15 mg/mL) and effectively inhibited acetylcholinesterase, butyrylcholinesterase, and 15-lipoxygenase (IC₅₀ = 0.11, 0.03, and 0.02 mg/mL, respectively). These results indicate that various blackcurrant matrices possess strong biological activity and may serve as promising functional food ingredients or sources of health-promoting compounds. Full article

Artemisia campestris is a medicinal plant species endemic to Algeria, particularly abundant in the southern regions and the central Sahara. Its long-standing use in traditional medicine has recently gained scientific attention, prompting further investigation into its bioactive potential. This study focuses on the phytochemical composition and biological activity of its hydromethanolic extract, with a particular emphasis on its ability to inhibit neural enzymes associated with insect physiology with particular relevance to Aphis gossypii (Glover), a major polyphagous agricultural pest. Preliminary screening revealed a diverse array of secondary metabolites, including tannins (catechic and gallic), flavonoids, quinones, glycosides, terpenoids, saponins, coumarins, and alkaloids; however, anthocyanins were not detected. Quantitative analysis confirmed high concentrations of total phenolics (80.91 ± 1.58 mg GAE/g), flavonoids (60.45 ± 2.02 mg RE/g), phenolic acids (4.24 ± 0.38 mg CAE/g), and condensed tannins (2.26 ± 0.29 mg CE/g). Enzyme inhibition assays were performed using Ellman’s method, and IC₅₀ values were calculated by nonlinear regression analysis based on dose–response curves. The extract demonstrated significant in vitro inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with IC₅₀ values of 13.79 ± 0.79 µg/mL and 8.34 ± 0.58 µg/mL, respectively. Molecular docking analyses further confirmed strong binding affinities of cyanidin-3-O-glucoside, malvidin-3-O-glucoside, and apigenin (−8.20 to −8.50 kcal/mol) with the AChE active site, stabilized by hydrogen bonding and π–π interactions with key residues. These results were benchmarked against galantamine, a reference inhibitor, which exhibited IC₅₀ values of 1.50 ± 0.12 µg/mL under the same conditions. Although galantamine showed superior potency, the relatively low IC₅₀ values of the A. campestris extract support its potential as a natural cholinesterase-inhibitory agent warranting further investigation. These findings suggest that A. campestris may represent a promising source of natural cholinesterase inhibitors with potential relevance for eco-friendly insect control. These in vitro and in silico findings provide a mechanistic rationale warranting future in vivo bioassay validation against A. gossypii and related agricultural pests. Full article

Coniferyl alcohol and coniferyl aldehyde are precursors of lignin and are used in spices and the pharmaceutical industry. In this work, antioxidant, anticholinergic, antidiabetic, and antiglaucoma effects of coniferyl alcohol and aldehyde were evaluated and compared against the standards. To determine the antioxidant capacities of coniferyl alcohol and aldehyde, ABTS^•+, DMPD^•+ and DPPH^• scavenging abilities as well as cupric ion (Cu²⁺) reduction, ferrous ions (Fe²⁺) reduction and Fe³⁺-TPTZ reduction activities were studied. Butylated hydroxytoluene (BHT), ascorbic acid, α-Tocopherol, Trolox, and butylated hydroxyanisole (BHA) were used as the standard antioxidants. When the antioxidant effects of coniferyl alcohol and coniferyl aldehyde are compared to the standards, they exhibit significant antioxidant effects. In addition, it was determined that coniferyl alcohol and coniferyl aldehyde had a high degree of inhibition effect towards carbonic anhydrase (hCA) I and II isoforms purified from human erythrocytes, α-glycosidase, butyrylcholinesterase (BChE), acetylcholinesterase (AChE), and α-amylase as in vitro and in silico. Molecular docking studies revealed favorable binding affinities of coniferyl alcohol and coniferyl aldehyde toward all investigated enzymes, with key hydrogen bonding and π–π interactions identified at the active sites. The docking findings were found to be compatible with the in vitro enzyme inhibition results, supporting the proposed multi-target biological potential of both compounds. Molecular docking studies revealed favorable binding affinities of coniferyl alcohol and coniferyl aldehyde toward all investigated enzymes. Key hydrogen bonding and π–π interactions were identified within the active sites, particularly for AChE and hCA II. The docking results were consistent with the in vitro enzyme inhibition data, supporting their multi-target biological potential. Docking demonstrated that both compounds can effectively interact with the catalytic regions of the target enzymes. The identified binding modes and interaction patterns support the observed inhibitory activities and provide a molecular basis for their multi-target biological effects. Full article

The genus Tamarix L. includes several species widely used in traditional medicine for their therapeutic properties. This study aims to evaluate the bioactive potential of Tamarix gallica extracts from Western Algeria using an integrated in vitro and in silico approach. GC–MS analysis with BSTFA derivatization was performed to characterize the chemical profile of the methanolic fraction. In addition, total phenolic, flavonoid, and tannin contents were determined in methanolic extracts of leaves and stems. The biological activities were assessed using antioxidant (DPPH, ABTS, β-carotene, FRAP, O-phenanthroline, and cupric reducing assays), antimicrobial, antidiabetic, and anti-Alzheimer in vitro assays. Molecular docking was conducted to evaluate the inhibitory potential of selected flavonoids against α-amylase, acetylcholinesterase, and butyrylcholinesterase. Results revealed a rich metabolite profile dominated by long-chain aliphatic alcohols (including hentriacontan-12-ol), phytosterols (β-sitosterol), fatty acids, phenolic derivatives, and sugar alcohols. The extracts exhibited strong antioxidant activity (IC₅₀ = 1.34 ± 0.43 and 12.32 ± 0.36 μg·mL⁻¹), significant antimicrobial effects against the tested pathogens, and notable antidiabetic and anticholinesterase activities (IC₅₀ = 78.65 ± 1.43 and 98.37 ± 1.07 μg·mL⁻¹). Molecular docking analysis supported these findings, showing strong binding affinities of quercetin and rhamnetin toward the target enzymes. Overall, T. gallica exhibits promising multifunctional bioactivities with potential pharmaceutical relevance. Full article

Compounds from olive (Olea europaea L.) and pomegranate (Punica granatum L.) have many beneficial effects on human health. This review paper considers the inhibitory potential, under in vitro conditions, of bioactive components of olive and pomegranate on different enzyme systems. Research shows that olive polyphenols (oleuropein, hydroxytyrosol, luteolin, and oleocanthal), as well as pomegranate polyphenols (punicalagin, urolithin A, ellagic acid), inhibit cyclooxygenase and lipoxygenase enzymes, which are associated with inflammatory processes. They also show an inhibitory effect on acetylcholinesterase, butyrylcholinesterase, and β-secretase, which opens up the possibility of a strong neuroprotective effect. Olive and pomegranate polyphenols also have an inhibitory effect on enzymes involved in carbohydrate metabolism, such as amylase and glucosidase, and can help fight diabetes and regulate human metabolism. In addition, polyphenols and extracts of both plants showed an inhibitory effect on cytochrome P450 enzymes, which metabolize most drugs. These data open up the possibility of interactions with certain groups of drugs. The current evidence supports the view that olive and pomegranate polyphenols act as biologically versatile compounds with considerable pharmaceutical and nutraceutical potential. Future investigations integrating enzymology, metabolomics, molecular docking, and clinical validation will be essential for translating these promising in vitro findings into evidence-based therapeutic applications. Full article

Luteolin and its derivative glycosides (cynaroside, orientin and isoorientin) are compounds with a flavonoid structure of plant origin. There are different studies in the literature on the antioxidant capacities of the structures and their inhibition effects on some enzymes. In this study, the antioxidant capacities of each structure were determined comparatively, and their inhibitory effects against enzymes associated with different diseases such as acetylcholinesterase, butyrylcholinesterase, α-glycosidase and α-amylase were evaluated by comparative investigation in vitro and in silico. Antioxidant capacities were determined for each structure by iron ions (Fe³⁺), cupric ions (Cu²⁺), Fe³⁺−Triphenyltetrazolium chloride (TPTZ) reduction methods and 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), N,N-dimethyl-p-phenylenediamine (DMPD) radical scavenging methods. According to the results obtained, it was determined that the antioxidant capacities of the structures were close to or better than butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), trolox, α tocopherol and ascorbic acid, which are used as standard antioxidants. The results of the study, which was conducted to determine the inhibition effects of the structures on the determined enzymes, were found to coincide experimentally and theoretically. According to the inhibition results, the best inhibitors were found as orientin (IC₅₀: 27.729 nM) for the human carbonic anhydrase I (hCA I), cynaroside (IC₅₀: 18.24 nM) for the human carbonic anhydrase I (hCA II), isoorientin (IC₅₀: 1.93 nM) for the acetylcholinesterase (AChE), and cynaroside (IC₅₀: 6.41 and 7.15 nM) for the butyrylcholinesterase (BChE) and α-glycosidase enzymes. Additionally, absorption, distribution, metabolism, and excretion (ADME) profiles and toxicity assessments of the structures were determined in a virtual environment. Full article

Plants of the genus Astragalus are recognized as rich sources of bioactive compounds with antioxidant and therapeutic potential; however, European species remain less explored than the well-known Astragalus membranaceus (Fisch.) Bunge. The aim of this study was to compare the phytochemical composition and in vitro biological activity of selected Astragalus species occurring in Poland (A. cicer L., A. glycyphyllos L., A. membranaceus). Phenolic compounds in methanolic extracts obtained from the roots and aerial parts were analyzed using spectrophotometric methods and UHPLC–DAD–ESI/TOF–MS. Antioxidant activity was evaluated using DPPH, ABTS, FRAP, CUPRAC, metal chelation, superoxide radical scavenging, and lipid peroxidation (TBARS) assays. Additionally, enzyme inhibition toward α-amylase, lipase, hyaluronidase, tyrosinase, and butyrylcholinesterase was assessed. The root of A. membranaceus exhibited the highest total phenolic content (199.84 ± 3.64 mg GAE/g extract) and the strongest antioxidant activity (DPPH IC₅₀ = 36.53 ± 1.22 µg/mL; ABTS IC₅₀ = 26.31 ± 0.03 µg/mL), as well as the most pronounced α-amylase inhibition (IC₅₀ = 17.78 ± 1.16 µg/mL). It also demonstrated moderate protective effects against AAPH-induced lipid peroxidation. The herb of A. cicer showed moderate radical scavenging capacity and the most effective inhibition of lipid peroxidation at higher concentrations. Extracts of A. glycyphyllos displayed weaker radical scavenging but notable metal-chelating properties. Selected extracts also exhibited moderate inhibitory activity against tyrosinase and butyrylcholinesterase. A. membranaceus remains the most potent source of phenolic compounds and antioxidant activity; European species such as A. cicer and A. glycyphyllos represent promising, locally available alternatives and may be used in phytotherapy and functional products. Full article

Background: Sambucus ebulus L. berries contain numerous bioactive compounds, but their volatile molecular composition has not yet been fully characterized. In this study, we analyzed the volatile components of the essential oil and aqueous infusion prepared from dried S. ebulus fruits, followed by multitarget in silico analysis of the major compounds against the following enzymes implicated in neuroinflammation and oxidative stress, namely cyclooxygenase-2 (COX2), monoamine oxidases (MAO-A and MAO-B), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), for which inhibitory activity of plant-derived compounds has previously been reported. Methods: Steam distillation, gas chromatography-mass spectrometry (GC-MS), and gas chromatography-flame ionization detection (GC-FID) were employed for compound isolation and analysis. Molecular docking studies were performed using Schrödinger software (version 2025-1). Results: Fatty acid esters and hexahydrofarnesyl acetone predominated in the essential oil, whereas linalool was identified as the major constituent of the infusion. MAO-A was predicted to be the most favorable interaction target for hexahydrofarnesyl acetone and other major constituents. Conclusions: Our findings expand the currently limited available data on the volatile composition of S. ebulus fruits and characterize the volatile profile of its fruit infusion for the first time. The in silico analyses suggest that S. ebulus volatile constituents may interact with several target enzymes implicated in neurodegeneration and inflammation. Full article

Larrea ameghinoi Speg., an endemic species of Argentine Patagonia traditionally used in folk medicine to treat fever, stomach disorders, respiratory conditions, back pain, and as an emmenagogue, among others, still remains chemically and biologically underexplored compared to the other four members of the genus. This study aimed to perform a comprehensive metabolomic characterization of methanolic extracts from two populations (EMLaSAO and EMLaMAQ) using ultra-high-resolution liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC–ESI–QTOF–MS) and to evaluate their antioxidant, antimicrobial, and enzyme-inhibitory activities of relevance to human health. Thirty-three compounds were tentatively identified by extensive UHPLC–MS analysis, including flavones, two major lignans, and oleanane-type triterpenes. Both extracts exhibited high phenolic content (215–239 mg of gallic acid equivalents (GAE)/g extract) and strong free radical scavenging activity, as evidenced by 2,2-diphenyl-1-picrylhydrazyl (DPPH, EC₅₀ ≈ 10 μg/mL), ferric-reducing antioxidant power (FRAP), and Trolox equivalent antioxidant activity (TEAC) assays. In addition, significant inhibition of butyrylcholinesterase (IC₅₀ ≈ 50 μg extract/mL) and α-glucosidase, together with selective antibacterial activity against methicillin-sensitive and resistant Staphylococcus aureus (MIC = 125 μg extract/mL), were recorded. These findings suggest that L. ameghinoi possesses a distinctive phytochemical composition conferring multitarget bioactivity, differing from other Larrea species dominated by lignans such as nordihydroguaiaretic acid (NDGA) and its derivatives. Overall, this work supports the potential of L. ameghinoi as a novel source of bioactive metabolites for managing oxidative stress-related disorders and opportunistic infections. This warrants future in vivo studies investigating biological activities associated with oxidative stress and their relevance to human health. Full article

As key therapeutic targets for symptomatic treatment of Alzheimer’s disease (AD) according to the cholinergic hypothesis, acetylcholinesterase (AChE; EC 3.1.1.7) and butyrylcholinesterase (BChE; EC 3.1.1.8) have been the subject of numerous studies over decades, leading to large collections of different ligands with corresponding AChE and BChE activity. This vast amount of data provides an ideal basis for the implementation of different machine learning (ML) and deep learning (DL) tools in different steps of the drug discovery process. Mainly applied to identify potential strong inhibitors of AChE and to a lesser extent BChE, many quantitative structure–activity relationship (QSAR) models and other predictive tools have been constructed utilizing different ML algorithms and DL techniques with various success depending on the input data and specific context. Here, we provide an extensive overview of such cases reported in the literature in recent years. Full article

This study investigated the chemical composition of the essential oil (EO) and the phenolic profiles of methanol extracts from Satureja boissieri Hausskn. ex Boiss. EO analysis by Gas Chromatography–Mass Spectrometry (GC-MS) identified carvacrol (45.2%), cymene (26.0%) and γ-terpinene (17.5%) as the primary constituents. Phenolic profiles were quantified via Liquid Chromatography–High-Resolution Mass Spectrometry (LC-HRMS), revealing syringic acid (56,647.96 mg/kg extract), rosmarinic acid (47,777.98 mg/kg extract) and hesperidin (6353.49 mg/kg extract) as major components in the extract. The antioxidant potential was evaluated through three distinct radical scavenging assays (DPPH, ABTS and DMPD) and the determination of ferric (Fe³⁺) and cupric (Cu²⁺) reducing capacities. Notably, S. boissieri exhibited potent antioxidant activity, with IC₅₀ values of 11.74 µg/mL for DPPH and 9.90 µg/mL for ABTS radical scavenging, demonstrating performance comparable to standard antioxidants such as α-tocopherol (11.31 and 8.37 µg/mL, respectively). Furthermore, the in vitro inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes were evaluated. While both extracts exhibited similar and significant AChE inhibition (35.3% and 32.4%, respectively), the essential oil was notably more potent against BChE than the methanol extract. These findings suggest that S. boissieri is a significant source of bioactive compounds with promising antioxidant and neuroprotective potential for pharmaceutical applications. Full article

Selected organic sunscreens from different chemical families were investigated in the context of their ability to inhibit butyrylcholinesterase using novel Multiple Linear Regression, Artificial Neural Network, and Support Vector Regression models based on a set of six independent variables commonly associated with compounds’ absorption and distribution properties. It was established that the descriptors that have a particularly strong, positive influence on the ability of compounds to inhibit BChE expressed as pIC₅₀ are the count of rotatable bonds (nRot) and lipophilicity (logD); pIC₅₀ is negatively correlated with flexibility (Flex), fraction of sp³ carbon atoms (F_sp3), caco-2 permeability (caco2), and plasma protein binding ability (PPB). The sunscreens that are likely to be particularly strong BChE inhibitors are Ethylhexyl Triazone (ET), Diethylhexyl Butamido Triazone (DOBT), Octocrylene (OCR), and Diethylamino Hydroxybenzoyl Hexyl Benzoate (DHHB). However, it must be stressed that ET and DOBT lie outside the chemical space of the reference compounds, so predictions for these two compounds should be treated with caution. Full article

This study explored the impact of ethanol as a co-solvent in supercritical fluid extraction on the recovery of bioactive compounds from carrot seeds and assessed the resulting extracts for antimicrobial, α-amylase and α-glucosidase, and butyrylcholinesterase inhibitory potential. Ethanol supplementation significantly improved extraction performance, with the yield increasing from 110 mg in the absence of ethanol to 134 mg at 5% ethanol, followed by a slight decrease to 132 mg at 10%. High-performance liquid chromatography (HPLC) revealed pronounced phytochemical enrichment at 5% ethanol, particularly for chlorogenic acid (1541.24 µg/g), gallic acid (1279.27 µg/g), and hesperetin (1513.68 µg/g), indicating enhanced recovery of phenolic and flavonoid constituents. The 5% ethanol extract demonstrated superior antimicrobial activity, producing inhibition zones of 19 mm against Enterococcus faecalis, 26 mm against Klebsiella pneumoniae, 25 mm against Staphylococcus aureus, and 29 mm against Candida albicans. Values of both minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were markedly reduced, while antibiofilm activity reached 93.11% for E. faecalis and 91.00% for K. pneumoniae. The extract also exhibited potent inhibitory effects with IC₅₀ values of 7.74 and 13.37 µg/mL, against α-amylase and α-glucosidase, correspondingly, as well as strong butyrylcholinesterase inhibition (IC₅₀ = 2.51 µg/mL), highlighting promising α-amylase/α-glucosidase and butyrylcholinesterase inhibitory potential. Molecular docking further supported these findings, showing that chlorogenic acid bound more strongly than vanillin to OmpK36, lysosomal acid-α-glucosidase, and butyrylcholinesterase, with docking scores ranging from −6.1 to −6.9 kcal/mol. These findings identify ethanol-modified supercritical fluid extraction as a sustainable and effective green strategy for improving the recovery of carrot seed bioactives and enhancing their multifunctional in vitro biological properties. Notably, this study provides the first comprehensive evidence that 5% ethanol modification selectively enriches key phenolic constituents, including chlorogenic acid, gallic acid, and hesperetin, in carrot seed extracts, with corresponding enhancement of α-amylase, α-glucosidase, and butyrylcholinesterase inhibitory activities. Full article

Alzheimer’s disease (AD) is a common neurodegenerative disorder linked to cholinergic dysfunction, with butyrylcholinesterase (BChE) being a key therapeutic target for moderate–severe AD. Cortex Mori Radicis, a traditional Chinese medicinal herb, is rich in Diels–Alder adducts with potential neuroprotective effects; here, eighteen Diels–Alder adducts (four new: morusalbanol B–E, 1–4) were isolated and identified from its 80% ethanol extract. Their cholinesterase inhibitory activities were assessed via Ellman’s method, with enzyme kinetics and molecular docking performed for active compounds. Most compounds showed selective BChE inhibition, with kuwanon X (14) being the most potent (IC₅₀ = 2.3 μM). morusalbanol B (1), cathayanon A (8), and kuwanon G (12) acted as noncompetitive inhibitors, while Morusalbanol C (2) and kuwanon X (14) were mixed competitive inhibitors. Molecular docking suggested that potent inhibitors occupied the BChE active pocket via hydrogen bonds, π-π stacking, and hydrophobic interactions with Trp82, His438, and Phe329. MD simulations and MM-GBSA binding free energy analysis further verified that all three representative complexes (1, 8, and 14) achieved favorable thermodynamic and structural stability, with binding driven primarily by van der Waals forces. Residue decomposition revealed that Trp82 and Phe329 served as core binding hotspots for all tested inhibitors. Structure–activity analysis indicated that a cis-trans methylcyclohexene configuration, shorter aliphatic ester chains, and more prenyl groups enhanced BChE inhibition. This study provides new lead compounds and a systematic molecular mechanism basis for developing novel anti-AD BChE inhibitors from natural products. Full article

A novel series of hybrid tetrahydro-β-carboline (THβC)-imidazolium (IM) salts incorporating a fused diketopiperazine scaffold was designed, synthesized, and evaluated as cholinesterase inhibitors for potential application in Alzheimer’s disease. The molecular design integrates a π-conjugated THβC core with a cationic IM moiety to promote dual-site interactions within the acetylcholinesterase (AChE) active-site gorge. All compounds exhibited micromolar inhibitory activity against AChE and butyrylcholinesterase (BChE), with a pronounced preference for AChE. The most active derivative, 12d, showed an IC₅₀ value of 0.72 μM toward AChE, while compound 12c demonstrated the highest selectivity (SI = 8.4). Structure–activity relationship studies revealed that both stereochemistry and N-alkyl chain length are critical determinants of activity, with S,S-configured derivatives consistently outperforming their R,R-configured analogs. In silico ADMET analysis indicated favorable physicochemical properties and predicted central nervous system permeability, although potential hepatotoxicity highlights the need for further optimization. Molecular docking studies suggested that the most promising compound adopts a dual-binding mode, interacting with both the peripheral anionic site and catalytic active site of AChE. These results identify THβC-IM hybrids as a structurally novel and promising scaffold for the development of selective cholinesterase inhibitors, providing a basis for further optimization toward multifunctional anti-Alzheimer agents. Full article