Search Results (480)

Inonotus obliquus, a medicinal mushroom valued for its bioactive compounds, has not been previously characterized from Romanian sources. This study presents the first comprehensive chemical and biological screening of I. obliquus, introducing novel polymer-based encapsulation systems to enhance the stability and bioavailability of its bioactive constituents. Two distinct delivery systems were designed to enhance the functionality of I. obliquus extracts: (i) microencapsulation in maltodextrin (MIO) and (ii) a sequential approach involving preparation of silver nanoparticle-loaded I. obliquus (IO–AgNPs), followed by microencapsulation to yield the hybrid MIO–AgNP system. Comprehensive metabolite profiling using GC–MS and ESI–QTOF–MS revealed 142 bioactive constituents, including terpenoids, flavonoids, phenolic acids, amino acids, coumarins, styrylpyrones, fatty acids, and phytosterols. Structural integrity and successful encapsulation were confirmed by XRD, FTIR, and SEM analyses. Both IO–AgNPs and MIO–AgNPs demonstrated potent antioxidant activity, significant acetylcholinesterase inhibition, and robust antimicrobial effects against Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, and Escherichia coli. Cytotoxicity assays revealed pronounced activity against MCF-7, HCT116, and HeLa cell lines, with MIO–AgNPs exhibiting superior efficacy. The synergistic integration of maltodextrin and AgNPs enhanced compound stability and bioactivity. As the first report on Romanian I. obliquus, this study highlights its therapeutic potential and establishes polymer-based nanoencapsulation as an effective strategy for optimizing its applications in combating microbial resistance and cancer. Full article

The present study investigated the neuroprotective potential of the Murraya carbazole derivatives murrayanol, mahanimbine, murrayafoline A, and 9-methyl-9H-carbazole-2-carbaldehyde using in silico and in vitro assays. The pharmacokinetic properties and potential toxicity (ADME/T) of the carbazole derivatives were assessed to evaluate their prospects as up-and-coming drug candidates. Molecular docking was used to investigate the interactions of the compounds with Aβ (PDB: 1IYT, 2BEG, and 8EZE) and AChE receptors (PDB: 4EY7 and 1C2B). The results from the in vitro assays were used to validate and support the findings from the in silico assays. The compounds demonstrated significant inhibition of acetylcholinesterase (AChE), a key target in neurodegenerative disorders. Murrayanol and mahanimbine presented superior inhibitory activity (IC₅₀ ~0.2 μg/mL), outperforming the reference drug, galantamine. The inhibition mechanisms were competitive (murrayanol, murrayafoline A, and 9-methyl-9H-carbazole-2-carbaldehyde) and non-competitive (mahanimbine), supported by low Ki values and strong docking affinities. The compounds also proved effective in reducing Aβ fibrillization (murrayanol: 40.83 ± 0.30%; murrayafoline A: 33.60 ± 0.55%, mahanimbine: 27.68 ± 2.71%). These findings highlight Murraya carbazoles as promising scaffolds for multifunctional agents in AD therapy. Further optimization and mechanistic studies are warranted to advance their development into clinically relevant neuroprotective agents. Full article

Background: Pharmaceutical compounds frequently co-occur in environmental waters, but studies on their combined effects on animals and humans remain limited. The present study investigated the individual and combined short-term effects of ketoprofen (Kp, a nonsteroidal anti-inflammatory drug inhibiting cyclooxygenase-2), valproic acid (VPA, an anticonvulsant acting as a voltage-gated sodium channel modulator), and meropenem (Mp, a β-lactam antibiotic) at environmentally relevant concentrations on zebrafish behavior, acetylcholinesterase (AChE) activity, and oxidative status. Methods: Adult zebrafish were exposed for 4 days to Kp, VPA, Mp, and their binary and ternary mixtures. Behavioral effects were assessed using 3D novel tank and social behavior tests, while the oxidative stress response was assessed through malondialdehyde (MDA) content, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. Results: Zebrafish exposed to Mp showed a notable increase in immobility, whereas those exposed to VPA and Mp + Kp exhibited a significant augmentation of average velocity and counter-clockwise rotations. All treated groups exhibited a notable increase in the time spent near the walls (thigmotaxis), and except for the control and Mp-exposed zebrafish, the other groups mostly stayed in the bottom tank zone (geotaxis). Kp, VPA + Kp, and VPA + Mp + Kp treatments impaired social behavior, with zebrafish displaying less interest in conspecifics. Biochemical analysis demonstrated that both the individual drugs and their combination caused oxidative stress, characterized by decreased GPx activity and increased SOD activity and MDA levels. Moreover, AChE activity was more strongly inhibited in zebrafish exposed to the binary and ternary mixtures than to individual drugs. Conclusions: The results indicate that acute exposure to individual and/or combined pharmaceuticals induces behavioral changes, oxidative damage, and AChE inhibition in zebrafish, highlighting the need to assess the effects of pharmaceutical mixtures for comprehensive ecosystem risks evaluation. Full article

Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder with a pressing need for novel therapeutics. However, current medications only offer symptomatic relief, without tackling the underlying pathology. To explore the bioactive potential of marine-derived fungi, this study focused on Aspergillus terreus C23-3, a strain isolated from the coral Pavona cactus in Xuwen County, China, which showed a richer metabolite fingerprint among the three deposited A. terreus strains. AntiSMASH analysis based on complete genome sequencing predicted 68 biosynthetic gene clusters (BGCs) with 7 BGCs synthesizing compounds reported to have anti-AD potential, including benzodiazepines, benzaldehydes, butenolides, and lovastatin. Liquid chromatography coupled with mass spectrometry (LC-MS)-based combinational metabolomic annotation verified most of the compounds predicted by BGCs with the acetylcholinesterase (AChE) inhibitor territrem B characterized from its fermentation extract. Subsequently, molecular docking showed that these compounds, especially aspulvione B1, possessed strong interactions with AD-related targets including AChE, cyclin-dependent kinase 5-p25 complex (CDK5/p25), glycogen synthase kinase-3β (GSK-3β), and monoamine oxidase-B (MAO-B). In conclusion, the genomic–metabolomic analyses and molecular docking indicated that C23-3 is a high-value source strain for anti-AD natural compounds. Full article

Due to the roles of oxidative stress, inflammation, and neurotransmitter imbalances in cognitive and mental dysfunction, we aimed to develop a functional drink with antioxidant and anti-inflammatory properties as well as the potential to support neurotransmitter balance for improved cognition and mental health. The Teng Mo, Fen Hong Mee, and Hong Chon Su guava varieties were screened for their polyphenol and flavonoid contents, antioxidant and anti-inflammatory effects, and suppressive effects on acetylcholinesterase (AChE), monoamine oxidase (MAO), GABA transaminase (GABA-T), and glutamate decarboxylase (GAD). Juice from the cultivar with the highest potential was selected and mixed with mint and honey syrups, pomelo-derived dietary fiber, ascorbic acid, agar, water, and fruit puree (pear/apple/orange) to create three guava jelly drink formulations. The formulation with pear puree showed the highest biological potential and was selected as the final product. It is rich in vitamin C, gallic acid, and dietary fiber, and provides approximately 37 Kcal/100 g. It also promotes the growth of lactic acid-producing bacteria in the culture. Thus, our drink shows the potential to reduce oxidative stress and inflammation, improve neurotransmitter regulation, and stimulate the gut–brain axis, thereby promoting cognition and mental wellness. However, clinical research is essential to confirm these potential benefits. Full article

Background/Objectives: Verbena officinalis L. (common vervain) is a medicinal plant traditionally used and investigated in phytotherapy for its neuroprotective, antioxidant, and anti-inflammatory properties. This study aims to investigate the phytochemical diversity and biological activity of V. officinalis extracts prepared with different ratios of butanol and ethanol. Methods: Aerial parts of V. officinalis were extracted using four solvent systems: 100% butanol (B1), 75:25 (BE7.5), 50:50 (BE5), and 25:75 (BE2.5) butanol:ethanol mixtures. Metabolite profiling was conducted using liquid chromatography–high-resolution tandem mass spectrometry (LC-HRMS/MS). Antioxidant activities were evaluated through six assays: 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), cupric ion-reducing antioxidant capacity (CUPRAC), ferric-reducing antioxidant power (FRAP), metal-chelating ability (MCA), and the phosphomolybdenum assay (PMA). Enzyme inhibition assays targeted acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase, and α-amylase. Antibacterial activity against Pseudomonas aeruginosa was tested via microdilution, while dominant phytochemicals were evaluated for binding affinity through molecular docking. Results: Seventy-five compounds, including phenolic acids, flavonoids, iridoids, phenylethanoids, and xanthones, were identified. BE5 extract exhibited the highest total phenolic content and strongest antioxidant capacity, while BE2.5 demonstrated the greatest antibacterial and metal-chelating effects. All extracts showed comparable AChE inhibition, with BE5 achieving the strongest tyrosinase and α-amylase inhibition. Docking studies confirmed high binding affinities of luteolin glucuronides to human and bacterial target enzymes. Conclusions: Solvent composition markedly influenced the chemical and biological profiles of V. officinalis extracts. BE5 and BE2.5 emerged as promising systems for obtaining bioactive fractions with therapeutic potential. Full article

Foeniculum vulgare Mill. (Apiaceae) is an aromatic medicinal plant known for its anti-inflammatory, antispasmodic, antiseptic, carminative, diuretic, and analgesic properties. This study aimed to investigate the effects of F. vulgare essential oil (FVEO; 25, 150, and 300 μL/L) on the cognitive performance and brain oxidative stress in a scopolamine (SCOP; 100 μM)-induced zebrafish model of cognitive impairment. Additionally, the pharmacokinetic properties and bioactivity profiles of the main FVEO constituents were predicted to be used in silico tools, including SwissADME, pkCSM, PASS online, and ADMETlab 2.0. Behavioral assays, novel tank diving test (NTT), Y-maze, and novel object recognition (NOR) test, were used to evaluate anxiety-like behavior, spatial memory, and recognition memory, respectively. Biochemical assessments of acetylcholinesterase (AChE) activity and oxidative stress biomarkers were also conducted. The results demonstrated that FVEO significantly improved cognitive performance in SCOP-treated zebrafish, normalized AChE activity, and reduced oxidative stress in the brain. These findings suggest the therapeutic potential of FVEO in ameliorating memory impairment and oxidative damage associated with neurodegenerative disorders such as Alzheimer’s disease (AD). Full article

Aloysia triphylla is widely used in traditional medicine from Peru for its sedative, digestive and anti-inflammatory properties. However, comprehensive studies on the biological activities of its essential oil (EO), particularly from Peruvian sources, remain limited. This study aimed to analyze the chemical composition and enantiomeric profile of A. triphylla EO and evaluate its antibacterial, antioxidant, anticholinesterase, and cytotoxic activities. The EO was obtained by steam distillation and analyzed using gas chromatography–mass spectrometry (GC-MS). A total of 62 compounds were identified, with (E)-caryophyllene (16.80%), β-pinene (9.96%), and germacrene D (10.00%) being the major components. Enantiomeric analysis revealed specific chiral signatures, including (−)-α-pinene, (+)-limonene, and (R)-(−)-linalool. The EO exhibited significant antibacterial activity, particularly against Bacillus subtilis (MIC = 5 µg/mL), and weak antioxidant activity (IC₅₀ = 7720 and 4648 µg/mL for DPPH and ABTS, respectively). Additionally, the EO demonstrated moderate acetylcholinesterase inhibition (IC₅₀ = 87.8 µg/mL) and cytotoxicity in the Artemia salina assay (LC₅₀ = 964 µg/mL). These findings suggest that A. triphylla EO possesses promising bioactivities with potential applications in pharmaceutical and cosmetic fields. Full article

Neurodegenerative diseases (NDDs), including Alzheimer’s disease (AD) and Parkinson’s disease (PD), are characterized by progressive neuronal dysfunction and loss and represent a significant global health challenge. Oxidative stress, neuroinflammation, and neurotransmitter dysregulation, particularly affecting acetylcholine (ACh) and monoamines, are key hallmarks of these conditions. The current therapeutic strategies targeting cholinergic and monoaminergic systems have some limitations, highlighting the need for novel approaches. Metallodrugs, especially ruthenium and platinum complexes, are gaining attention for their therapeutic use. Among metal complexes, gold(I) and silver(I) N-heterocyclic carbene (NHC) complexes exhibit several biological activities, but their application in NDDs, particularly as monoamine oxidase (MAO) inhibitors, remains largely unexplored. To advance the understanding of this field, we designed, synthesized, and evaluated the biological activity of a new series of Au(I) and Ag(I) complexes stabilized by NHC ligands and bearing a carboxylate salt of tert-butyloxycarbonyl (Boc)-N-protected proline as an anionic ligand. Through in silico and in vitro studies, we assessed their potential as acetylcholinesterase (AChE) and MAO inhibitors, as well as their antioxidant and anti-inflammatory properties, aiming to contribute to the development of potential novel therapeutic agents for NDD management. Full article

In this study, we investigated the potential of a three-mushroom complex extract (GMK) to inhibit neuronal cell death induced by the activation of AMPA and NMDA receptors following glutamate treatment in NGF-differentiated PC12 neuronal cells. GMK significantly mitigated glutamate-induced excitotoxic neuronal apoptosis by reducing the elevated expression of BAX, a critical regulator of apoptosis, and restoring BCL2 levels. These neuroprotective effects were associated with redox regulation, as evidenced by the upregulation of SOD, CAT, and GSH levels, and the downregulation of MDA levels. Mechanistic studies further revealed that GMK effectively scavenged ROS by downregulating NOX1, NOX2, and NOX4, while upregulating NRF1, P62, NRF2, HO1, and NQO1. Additionally, in the same model, GMK treatment increased acetylcholine, choline acetyltransferase, and GABA levels while reducing acetylcholinesterase activity. These effects were also attributed to the regulation of redox balance. Furthermore, we investigated the antioxidant and anti-inflammatory mechanisms of GMK in LPS-stimulated BV2 microglia. GMK inhibited the activation of IκB and MAPK pathways, positively regulated the BCL2/BAX ratio, suppressed TXNIP activity, and upregulated NQO1 and NOX1. In conclusion, GMK improved neuronal excitotoxicity and microglial inflammation through the positive modulation of the redox regulatory system, demonstrating its potential as a natural resource for pharmaceutical applications and functional health foods. Full article

The distribution of Amaryllidaceae alkaloids, with a focus on their chemodiversity, has been reported previously, but not at a genera-wide diversity level. This review provides a comprehensive survey of the occurrence of Amaryllidaceae alkaloids across the genera of the Amaryllidaceae family. This survey is taxonomically guided by the National Center for Biotechnology Information (NCBI) Taxonomy Browser, with targeted keyword searches conducted in the Chemical Abstracts Service (CAS) SciFinder-n and PubMed. The family Amaryllidaceae comprises over 1214 species across three subfamilies: Agapanthoideae (1 genus, 5 species), Allioideae (3 genera plus 11 subgenera, 617 species), and Amaryllidoideae (58 genera plus 13 subgenera, 592 species). Amaryllidaceae alkaloids have been identified exclusively in 36 of the 58 genera and 6 of the 13 subgenera within the Amaryllidoideae subfamily. To date, more than 600 Amaryllidaceae alkaloids have been isolated, predominantly from this subfamily—hence the designation “Amaryllidaceae alkaloids”. These alkaloids display a wide spectrum of biological activities, including acetylcholinesterase inhibition, anti-inflammatory, antioxidant, antimicrobial, antidiabetic, and anticancer effects. A notable example is galanthamine (also known as galantamine), an FDA-approved drug marketed under the brand names Reminyl™ (Janssen Research Foundation, Beerse, Belgium, 2001) and Razadyne™ (Johnson & Johnson Pharmaceutical Research, New Brunswick, NJ, USA, 2004) for the treatment of mild to moderate Alzheimer’s disease, due to its potent acetylcholinesterase-inhibitory activity. Galanthamine has been isolated from species belonging to the genera Cyrtanthus, Galanthus, Leucojum, Lycoris, Narcissus, Ungernia, Chlidanthus, Crinum, Eucharis, Eustephia, Pancratium, and Phaedranassa. Lycorine is another widely distributed alkaloid found across multiple genera, and it has been extensively studied for its diverse bioactivities. Given the remarkable chemical diversity and bioactivity of Amaryllidaceae alkaloids, along with the many underexplored genera and species, further research into Amaryllidaceae species and their alkaloids is strongly warranted to support the discovery and development of novel therapeutic agents. Full article

(−)-Patagonic acid (1) is a clerodane diterpene isolated from several plants from the Alismataceae, Asteraceae, Euphorbiaceae, Fabaceae, Lamiaceae, Salicaceae, Sapindaceae, and Velloziaceae families, and its biological potential as an inhibitor of butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) and as an anti-inflammatory compound has been described. Furthermore, the enantiomer (+)-1 is also described in Fabaceae and Verbenaceae. A lack of formal studies about the absolute configuration (AC) determination of 1 is emphasized. Thus, the present manuscript describes the AC determination of patagonic acid (1). The chemical correlation of (−)-1 from (−)-hardwickiic acid (2) was achieved by a simplistic oxidative process. The specific rotation value and electronic circular dichroism (ECD) analysis allowed for the AC determination of (−)-1 as (5R,8R,9S,10R)-(−)-patagonic acid. ECD revealed a positive exciton chirality (EC) phenomenon in both (−)-1 and (−)-2, which is directly associated with their configuration and conformational preferences, which were assessed by DFT calculations at the B3LYP/DGDZVP level of theory. Since the NMR data of (+)-1 are fully coincident with those from its enantiomer studied herein, the chirality of (5S,8S,9R,10S)-(+)-patagonic acid could also be determined. These experimental conclusions deeply complement the literature related to clerodane compounds biosynthesized in several families of plants of scientific interest. Full article

Current therapies for Alzheimer’s disease (AD) includes acetylcholinesterase inhibitors, NMDA receptor antagonists, and amyloid beta (Aβ)/Tau-targeting drugs. While these drugs improve cognitive decline and target the pathological mechanisms, their outcomes still are still in debate. Mesenchymal stem cells (MSCs) offer a regenerative approach by modulating neuroinflammation and promoting neuroprotection. Although the paracrine of MSCs is efficient in various AD preclinical studies and the exosomes of MSCs have entered clinical trials, the key cytokines driving the efficacy remain unclear. Here, we evaluated human umbilical cord-derived MSCs (hUC-MSCs) and employed gene-silenced MSCs (siHGF-MSCs, siTNFR1-MSCs, siBDNF-MSCs) in APP/PS1 AD mice to investigate specific mechanisms. hUC-MSCs significantly reduced Aβ/Tau pathology and neuroinflammation, with cytokine-specific contributions: silencing HGF predominantly reduced Aβ/Tau clearance, although silencing TNFR1 or BDNF showed modest effects; silencing TNFR1 or BDNF more prominently weakened anti-neuroinflammation, while silencing HGF exerted a weaker influence. All three cytokines partially contributed to oxidative stress reduction and cognitive improvements. Our study highlights MSC-driven AD alleviation as a multifactorial strategy and reveals specific cytokines alleviating different aspects of AD pathology. Full article

Eleutherococcus senticosus (ES) has been used in traditional medicine for immune-boosting, stress-reducing, and endurance-enhancing properties. In this study, the chemical composition and biological activity of polar and non-polar fractions obtained from 75% methanol E. senticosus roots extract were evaluated. Spectrophotometric methods were used to assess the antioxidant (DPPH, ABTS, FRAP, CUPRAC, O₂^•−) and anti-enzymatic (hyaluronidase, acetylcholinesterase, butyrylcholinesterase, α-amylase, and tyrosinase) activities. Metabolic profiling was carried out using HPLC-DAD and UHPLC-DAD/ESI-TOF-MS. The ethyl acetate fraction (EtOAc) showed the highest antioxidant activity with IC₅₀ values of 82.73 ± 0.065 µg/mL (DPPH) and 9.92 ± 0.17 µg/mL (ABTS). The EtOAc fraction also exhibited strong anti-enzymatic effects against hyaluronidase and α-amylase (125.24 ± 12.29 and 97.34 ± 9.18 µg/mL, resp.). In turn, the hexane fraction exhibited the most potent anti-AChE activity with IC₅₀ equal 245.72 ± 11.82 µg/mL. The HPLC-DAD analysis revealed the presence of caffeic acid derivatives. These results suggest that the ethyl acetate fraction may have therapeutic relevance in inflammation- and metabolic-related diseases. We perceive the potential of this fraction as a rich source of compounds with an anti-inflammatory activity; however, more advanced research in in vivo model is required. Full article

In this study, the ranking of the multifaceted activity of rutin (Ru), quercetin (Q), and quercetin’s glucosides (Q3G, Q4′G and Q3,4′G) was addressed. The antioxidant potency was determined by electrochemical methods, whereas the ability of these compounds to inhibit angiotensin-converting enzyme (ACE) activity, acetylcholinesterase (AChE) activity, and advanced glycation endproduct (AGE) formation was examined in bovine serum albumin (BSA)/glucose and BSA/methylglyoxal (MGO) model systems to show their importance against hypertension, Alzheimer-type dementia, and diabetic complication, respectively. Then, the relationship between the biological activities of these compounds and their antioxidant potential provided by the cyclic voltammetry (CV) method was evaluated. The ranking of the ACE inhibitory activity was Q > Q3,4′G > Ru > Q3G > Q4′G. The correlation coefficient between ACE enzyme inhibitory activities and antioxidant potentials had a value of r = −0.68, thus clearly indicating the impact of antioxidant potential and chemical structure on ACE inhibitory activity. The ranking of the AChE enzyme inhibitory activity was Q ≈ Q3G ≈ Q4′G ≈ Ru > Q3,4′G, and the correlation between their antioxidant potentials and AChE inhibitory activities (r = −0.77) also indicated the impact of chemical structure. The quercetin glucosides displayed strong inhibitory capacity on AGE formation, as the ranking of anti-AGE activity in the BSA/MGO model system was Q3,4′G ≈ Q4′G ≈ Q3G > Ru ≈ Q > AG. The anti-AGE activity of rutin, quercetin, and quercetin’s glucosides was negatively correlated with their IC₅₀ values for ACE inhibition (r = −0.67) and AChE inhibition (r = −0.81), whereas no correlation was found between their ACE and AChE inhibition activities. These effects of rutin, quercetin, and quercetin’s glucosides expand our knowledge of the multifunctional activity of biologically active compounds of plant origin. Full article