Ellagic Acid Research Articles

Characterization, Bioaccesibility and Antioxidant Activities of Phenolic Compounds Recovered from Yellow pea (Pisum sativum) Flour and Protein Isolate.

This study focused on studying the bioaccesible phenolic compounds (PCs) from yellow pea flour (F) and protein isolate (I). Total phenolic contents (TPC), PCs composition and antioxidant activities were analysed in ethanol 60% extracts obtained by applying ultrasound assisted extraction (UAE, 15min/40% amplitude). The preparation of I under alkaline conditions and the elimination of some soluble components at lower pH produced a change of PCs profile and antioxidant activity. After simulated gastrointestinal digestion (SGID) of both ingredients to obtain the digests FD and ID, notable changes in the PCs concentration and profiles could be demonstrated. FD presented a higher ORAC activity than ID (IC50 = 0.022 and 0.039mg GAE/g dm, respectively), but lower ABTS•+ activity (IC50 = 0.8 and 0.3mg GAE/g dm, respectively). After treatment with cholestyramine of extracts from FD and ID in order to eliminate bile salts and obtain the bioaccesible fractions FDb and IDb, ROS scavenging in H2O2-induced Caco2-TC7 cells was evaluated, registering a greater activity for ID respect to FD (IC50 = 0.042 and 0.017mg GAE/mL, respectively). These activities could be attributed to the major bioaccesible PCs: OH-tyrosol, polydatin, trans-resveratrol, rutin, (-)-epicatechin and (-)-gallocatechin gallate for FD; syringic (the most concentrated) and ellagic acids, trans-resveratrol, and (-)-gallocatechin gallate for ID, but probably other compounds such as peptides or amino acids can also contribute.

Longevity Spinach (Gynura procumbens) Ameliorated Oxidative Stress and Inflammatory Mediators in Cisplatin-Induced Organ Dysfunction in Rats: Comprehensive in vivo and in silico Studies.

This study focused to assess the efficacy of Gynura procumbens (GP) leaf extract against cisplatin (CP)-induced hepatorenal complications in Wister albino rats. Additionally, it aims to detect polyphenolic compounds using high-performance liquid chromatography with diode-array detection (HPLC-DAD). The rats were treated intraperitoneally with CP (7.5 mg/kg) to mediate hepatorenal damage. They were then treated with GP extract (75 and 150 mg/kg, P.O.) for 7 consecutive days. Although GP extract significantly ameliorated CP-mediated hepatorenal biomarkers like alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and blood urea nitrogen (BUN) levels in a dose-dependent manner, GP extract at 150 mg/kg dose normalized hepatorenal biomarkers ALP (45.11 U/L), ALT (34 U/L), AST (29 U/L), creatinine (10.3 mg/dl) and BUN (11.19 mg/dl) while comparing to control and disease group. Similarly, though it significantly reduced CP-induced oxidative stress inducers, including nitric oxide (NO) and advanced oxidative protein products (AOPP), higher dose (150 mg/kg) exhibited better activity in reducing NO (281.54 mmol/gm tissue in liver and 52.73 mmol/gm tissue in the kidney) and AOPP (770.95 mmol/mg protein in liver and 651.90 mmol/mg protein in the kidney). Besides, it showed better enhancement in the antioxidant enzymes superoxide dismutase, and glutathione levels at a higher dose (150 mg/kg). Histopathological studies showed that CP caused collagen accumulation in the liver and kidney tissues. GP extract drained the collagen mass and acted against hepatorenal damage. Ellagic acid, gallic acid, quercetin hydrate, kaempferol, and rutin hydrate were revealed in GP extract. In-silico modelling showed good docking scores of the polyphenolic compounds with molecular targets including CYP4502E1, NF-κB, caspase-3, and TNF-α. GP could be an effective therapeutic option for management of anticancer drugs' complications like CP-induced organ damage, although clinical studies are required to establish herbal formulation.

Efficient Lead Removal by Assembly of Bio-Derived Ellagate Framework, Which Enables Electrocatalytic Reduction of CO2 to Formate.

Lead (Pb) poisoning and CO2-induced global warming represent two exemplary environmental and energy issues threatening humanity. Various biomass-derived materials are reported to take up Pb and convert CO2 electrochemically into low-valent carbon species, but these works address the problems separately rather than settle the issues simultaneously. In this work, cheap, natural ellagic acid (EA) extracted from common plants is adopted to assemble a stable metal-organic framework (MOF), EA-Pb, by effective capture of Pb2+ ions in an aqueous medium (removal rate close to 99%). EA-Pb represents the first structurally well-defined Pb-based MOF showing selective electrocatalytic CO2-to-HCOO- conversion with Faradaic efficiency (FE) of 95.37% at -1.08V versus RHE. The catalytic mechanism is studied by 13CO2 labeling, in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), and theoretical calculation. The use of EA-Pb as an electrocatalyst for CO2 reduction represents a 2-in-1 solution of converting detrimental wastes (Pb2+) as well as natural resources (EA) into wealth (electrocatalytic EA-Pb) for addressing the global warming issue.

Antidiabetic effectiveness of Phyllanthus niruri bioactive compounds via targeting DPP-IV.

Phyllanthus niruri Linn. (Euphorbiaceae) is a small herb and is categorised as one of the rich medicinal plants throughout the world. This study aimed to evaluate the P. niruri L. whole plant extract (PNE) for secondary metabolite assay (total phenolic and terpenoid content) followed by the potential antioxidant activity (ABTS diammonium salt radical assay, DPPH· activity, superoxide anion (O2-) radicals' assay, and nitric oxide (NO) radical generation) and antidiabetic activity in vivo and in vitro in streptozotocin (STZ) induced albino mice. PNE showed good scavenging activity with a value of 286.45 ± 6.55 mg TE/g and 194.54 ± 4.64 mg TE/g in ABTS and DPPH assays respectively. In the superoxide anion assay, the PNE caused a dose-dependent inhibition at the lowest IC25 value of 0.17 ± 0.00 mg/mL compared to ascorbic acid (IC25 of 0.25 ± 0.02 mg/mL). The scavenging ability of PNE against nitric oxide showed an IC25 of 1.13 ± 0.04 mg/mL compared to ascorbic acid (IC25 4.78 ± 0.09 mg/mL). Unlike diabetic control mice, the PNE-treated diabetic mice presented significant amelioration of glycaemia and lipid dysmetabolism. Phytochemicals like Astragalin, Gallocatechin, Ellagic acid, Gallic acid, Brevifolin carboxylic acid, Phyllnirurin, and Hypophyllanthin showed significant docking score (> -4) of inhibitory potential with DPP-IV protein. Results indicated that PNE phytochemicals could be a promising antidiabetic agent by targeting DPP-IV.

Dry-air pretreatments effects on physiochemical properties, stability, antioxidants, phytosterol and tocopherol profiles of hemp oil

The study investigated effects of dry air pretreatment (DAP) at varying temperatures (160˚C, 180˚C, and 200˚C) and times (5-, 10-, 15-, and 20-min) on hemp oil (HeO) quality attributes. The total flavonoid (TfC) and phenolic (TpC) content, tocopherols, phytosterols, flavonoids, phenolic acids, oxidative stability index (OSI), colour attributes, Maillard products, fatty acid profile (FAP), physiochemical properties and radical scavenging activity (RsA) of HeO were studied. DAP had increased Maillard products, browning index, p-anisidine value, viscosity and ΔE while decreased peroxide, a* , b* and L* values of HeO. The TpC, TfC, RsA, phenolic acids (protocatechuic, 4-hydroxybenzoic, ellagic, chlorogenic, rosmarinic and trans cinnamic acids), epicatechin, total hydroxycinnamic and hydroxybenzoic acids and total flavonoids were highest in HeO upon DAP at 200 oC for 15 min. The tocopherols and phytosterols were highest upon DAP at 180 oC for 5 and 10 min, respectively. The highest HeO yield (25.85%) and OSI (6.80 h) was attained upon DAP at 180 oC and 200 oC for 10 min, respectively. In conclusion, the DAP had triggered a Maillard reaction, augmented the release of antioxidants, pigments and increased the OSI of HeO. The optimal DAP can be employed for the improvement of HeO quality attributes.

Phytochemical Profile and Bioactivity of Bound Polyphenols Released from Rosa roxburghii Fruit Pomace Dietary Fiber by Solid-State Fermentation with Aspergillus niger

This study aimed to investigate the phytochemical profile, bioactivity, and release mechanism of bound polyphenols (BPs) released from Rosa roxburghii fruit pomace insoluble dietary fiber (RPDF) through solid-state fermentation (SSF) with Aspergillus niger. The results indicated that the amount of BPs released from RPDF through SSF was 17.22 mg GAE/g DW, which was significantly higher than that achieved through alkaline hydrolysis extraction (5.33 mg GAE/g DW). The BPs released through SSF exhibited superior antioxidant and α-glucosidase inhibitory activities compared to that released through alkaline hydrolysis. Chemical composition analysis revealed that SSF released several main compounds, including ellagic acid, epigallocatechin, p-hydroxybenzoic acid, quercetin, and 3,4-dihydroxyphenylpropionic acid. Mechanism analysis indicated that the disruption of tight structure, chemical bonds, and hemicellulose was crucial for the release of BPs from RPDF. This study provides valuable information on the potential application of SSF for the efficient release of BPs from RPDF, contributing to the utilization of RPDF as a functional food ingredient.

Physicochemical Characterization, Antioxidant, and Proliferative Activity of Colombian Propolis Extracts: A Comparative Study.

Propolis extracts have been widely studied due to their popularity in traditional medicine, presenting incredible biodiversity. This study aimed to analyze propolis extracts' phytochemical, physicochemical, and biological activities from four different biogeographic zones of the Huila region (Colombia). The raw material samples were collected by the scraping method and the ethanolic extracts (EEPs) were obtained by cold maceration with ethanol (96%). The physicochemical and sensory characterization was carried out according to the protocols recommended by the Brazilian Ministry of Agriculture and the main components of the EEPs were identified by LC-HRMS analysis. The determination of total phenols and flavonoids was carried out using colorimetric techniques. The antioxidant activity, cytotoxicity, and cell cycle regulation analyses in L929 and HGnF cells were evaluated using DPPH, Alamar Blue, and 7-amino actinomycin D (7-AAD) assays. The propolis samples presented an average yield of 33.1%, humidity between 1.6 and 2.8%, melting point between 54 and 62 °C, ashes between 1.40 and 2.19%, and waxes of 6.6-17.9%, respectively. The sensory characteristics of all samples were heterogeneous, complying with the quality specifications established by international standards. The polyphenolic and total flavonoid content was representative in the samples from Quebradon (255.9 ± 9.2 mg GAE/g, 543.1 ± 8.4 mg QE/g) and Arcadia (543.1 ± 8.4 mg GAE/g, 32.5 ± 1.18 g QE/g) (p < 0.05) that correlated with high antioxidant activity (Quebradon: 37.2 ± 1.2 µmol/g, Arcadia: 38.19 ± 0.7 µmol/g). In the chemical composition analysis, 19 compounds were characterized as phenolic acids and flavonoids, the most representative being chrysoeriol-O-methyl-ether, ellagic acid, and 3,4-O-dimethylcaffeic acid. Regarding biological activity, Quebradon and Arcadia propolis presented low toxicity with IC50 of 2.83 ± 2.3 mg/mL and 4.28 ± 1.4 mg/mL in HGnF cells, respectively, and an arrest of the cell cycle in the G2/M phase of 71.6% and 50.8% compared to the control (11.9%) (p < 0.05). In general, the results of this study contribute to the identification of valid quality criteria to evaluate Colombian propolis, contributing to its study and chemical and biological characterization as a source of raw material for industrial and pharmaceutical use. In addition, Quebradon and Arcadia propolis can be important sources of bioactive molecules for the development of new drugs.

Effects of natural waste on in vitro oxidative DNA damage

In this study, the effects of natural waste products such as extracts from C. coggygria leaves and Punica granatum L. peels were investigated against oxidative DNA damage induced by Fenton reaction. 8-OH-2’dG as a general marker of DNA damage on thymus DNA, and the bioactive compounds of extracts were measured by LC-MS/MS. Our results had shown that ethanol extracts of C. coggygria leaf and Punica granatum L. peel had a protective effect on oxidative damaged DNA. It was determined that the bioactive compounds of C. coggygria leaves (gallic acid, protocatechuic acid, myricetin, syringic acid and ethyl gallate as a major compounds) and Punica granatum L. peel (ellagic acid, abscisic acid, ethyl gallate, phlorizin, gallic acid, myricetin as major compounds) may have an important role in the protective effect against oxidative DNA damage. Therefore, Cotinus coggygria leaves and Punica granatum L. peel may have potential use in medicine or cosmetic fields.

Anti-inflammatory Effect of the Hydroethanolic Extract from Dacryodes kukachkana Leaves in Mice: Role of Macrophage Nitric Oxide

Aims: This study aimed to characterize and evaluate the effect of the hydroethanolic extract from D. kukachkana leaves (HEDkL) in mice models of acute inflammation and in isolated macrophages stimulated with carrageenan, along with possible adverse effects in the central nervous system. Study Design: After characterization of phenolic constituents, HEDkL was injected in the animals 60 min before the administration of inflammatory stimulis. The anti-inflammatory effect of HEDkL was evaluated in the models of paw edema, peritonitis and air pouch and in peritoneal macrophages stimulated with carrageenan in vitro. The per se effect of HEDkL was evaluated for behavioral alterations. Place and Duration of Study: Higher Institute of Biomedical Sciences and Animal Health Research Center, State University of Ceara; Physiopharmacology Laboratory, Federal University of Acre; between March 2021 and March 2023. Methodology: The characterization of phenolic compounds was performed by HPLC-DAD. Swiss mice (25 - 35 g) received HEDkL (25 - 200 mg/kg; per oral) 60 min before carrageenan. Macrophages were incubated with HEDkL (100 - 200 µg/mL) before being stimulated.  The anti-inflammatory effect was assessed for edema, hypernociception, vascular permeability, leukocyte infiltrate, oxidative stress and inflammatory. Behavioral alterations (exploratory, anxiolytic, depressant activities) were evaluated in the animals treated with HEDkL (50 mg/kg). Results: The HPLC-DAD revealed the presence of ellagic acid, epicatechin and gallic acid. In the paw edema model, HEDkL (50 mg/kg) inhibited the edema late phase (2 - 5h) by 45% and the activity of the enzyme myeloperoxidase by 48%. In the peritonitis model, HEDkL (50 mg/kg) reduced leukocyte migration (45%), hypernociception (73%), total proteins (20%) and NO2-/NO3- (23%). In the air pouch model, HEDkL (50 mg/kg) reduced the migration of total leukocytes (76%) and neutrophils (88%). In vitro HEDkL (200 µg/mL) reduced by 31% the NO2-/NO3- in the supernatant of macrophages. HEDkL did not alter the animals exploratory, anxiolytic, or depressant behaviors. Conclusion: HEDkL containing flavonoids and phenols presents anti-inflammatory effect in vivo and in vitro involving nitric oxide inhibition, being devoid of behavioral alterations.

Unveiling the antimalarial properties of Terminalia ivorensis (A. Chev) stem bark aqueous extract: In vivo efficacy testing and in silico predictions

Due to the spreading resistance to antimalarial drugs, new therapeutics are urgently needed, preferably with novel modes of action. Extracts from Terminalia ivorensis have previously been shown to possess activity in vitro against multidrug-resistant and drug-sensitive strains of Plasmodium falciparum. However, to the best of our knowledge, no scientific study has been published describing the antimalarial potential of these extracts through in vivo efficacy testing. This study aimed to determine the safety and antimalarial efficacy of the T. ivorensis stem bark aqueous extract (TiH2O) in a mouse model using the OECD 423 protocol and the suppressive and curative murine malaria models, and to predict in silico the pharmacokinetic properties and drug-likeness of two major phytochemical constituents. The in vivo antimalarial efficacy was assessed using the P. berghei NK65-infected mice. The TiH2O treatment impact on biochemical parameters was measured using established standard procedures. The pharmacokinetics prediction was achieved through the pkCSM predictor and Swiss ADME. The TiH2O extract was nontoxic in BALB/c mice at a lethal dose of 50 (LD50) &gt; 2000 mg/kg. The TiH2O extract displayed strong antimalarial efficacy with 100% parasitemia suppression at 200 mg/kg b.w. after 4 days of treatment while its oral administration at 400 mg/kg b.w. in the curative model significantly decreased P. berghei parasitemia by 94.07% with a median efficacy dose (ED50) of 96.80 mg/kg. The administration of TiH2O extract restored the histological parameters disrupted by P. berghei, and the transaminase (ALT and AST) activity, creatinine, and bilirubin levels significantly decreased compared to the negative control mice. In silico explorations showed that the main constituents leucodelphidin (leucodelphinidin) and ellagic acid of the TiH2O extract have drug-like properties, thus indicating that T. ivorensis might constitute a promising source of antimalarial chemical entities with good pharmacokinetics and drug-like properties. The results obtained further corroborated the preliminary in vitro antiplasmodial studies of T. ivorensis stem bark aqueous extract. The metabolome of TiH2O extract should be further profiled in the prospects of characterizing novel natural product scaffolds to support antimalarial drug discovery.

Synthesis, characterization and biological applications of a new nano-sized binuclear copper(II) complex containing bathophenanthroline and ellagic acid as ligands

A new binuclear copper(II) complex, nano-[Cu2-(DIP)2-EA], was synthesized by using bathophenanthroline and ellagic acid ligands in a multi-component/one-pot method, and then characterized by electrospray ionization mass spectrometry (ESI-MS), Fourier transform infrared spectroscopy (FT-IR), ultraviolet-visible spectrophotometry (UV-vis), thermogravimetric analysis (TGA), and field emission scanning electron microscopy (FE-SEM). The antioxidant, antibacterial, and anticancer properties of the synthesized nano-[Cu2-(DIP)2-EA] were studied. The DPPH radical test pointed out that the nano-[Cu2-(DIP)2-EA] enjoys a good potential (28.4 %) to scavenge free radicals and the bacteria culture indicated a moderate ability of the complex to prevent the growth and proliferation of gram-positive bacteria (Staphylococcus aureus ATCC 29213) and gram-negative ones (Pseudomonas aeruginosa ATCC 27853). The cell culture displayed a superior ability of nano-[Cu2-(DIP)2-EA] to destroy breast cancer cells (MCF-7) compared to ellagic acid. In addition, the binding interaction of nano-[Cu2-(DIP)2-EA] with ct-DNA was studied in vitro (pH 7.40) by ultraviolet-visible absorption spectrophotometry, fluorescence emission spectrofluorimetry, circular dichroism (CD) spectropolarimetry, viscosity assessment technique, and molecular docking computer simulation. The results of the fluorescence enhancement spectra clearly showed a desirable affinity of nano-[Cu2-(DIP)2-EA] to ct-DNA. A hyperchromic effect was observed along with a slight red shift in the UV-visible spectra of nano-[Cu2-(DIP)2-EA]-DNA adduct, indicating that the nano-[Cu2-(DIP)2-EA] can form a conjugate with ct-DNA molecule. Thermodynamic properties exhibited an exothermic spontaneous formation of nano-[Cu2-(DIP)2-EA]-DNA adduct favored by H-bonds and van der Waals forces. The competitive emission investigations using methylene blue (MB) and Hoechst 33258 demonstrated that the binuclear copper(II) can replace the DNA-bound Hoechst and interact via minor grooves, as confirmed also by negligible viscosity alterations. The CD observations proposed that the nano-[Cu2-(DIP)2-EA] induces conformational changes in the ct-DNA. Molecular docking modeling results recognized a minor groove mechanism of nano-[Cu2-(DIP)2-EA] to interact with ct-DNA, and the complexation process is supported by H-bonds and van der Waals interactions.

Atlas pistachio (Pistacia atlantica) unripe fruit extract as a source of phytochemicals with anti-tyrosinase, antioxidant, and antibacterial properties

The current need for biologically active substances that are sustainable, allegedly beneficial to health, and may be employed as ingredients in cosmetic products has encouraged numerous researchers. Pistacia atlantica is known to contain compounds that possess strong biological effects beneficial to health. The objective of this study was the quantification of the polyphenols in unripe Atlas pistachio (AP) fruit extract and the evaluation of hydro-methanolic extract and anthocyanins for their antioxidant, anti-tyrosinase, and antimicrobial effects. The results revealed that the yield of the hydro-methanolic extract was 22.15%, characterized by 75.12 mg GAE/g DM for total phenolics and strong content of hydrolysable tannins (400.16 mg GAE/g DM). 1,1-dimethyl-allyl caffeate, hydroxytyrosol, ellagic acid, rutin, and kaempferol-3-O-glucoside were the most abundant components quantified by HPLC-DAD. The tyrosinase enzyme was significantly inhibited by AP extract (EC50 = 0.70 mg/mL). For the antioxidant properties, the hydrolyzed anthocyanin extract exhibited the best action against reducing power and β-carotene, compared to anthocyanins crude extract and fruits. This extract showed its stronger antibacterial activity. In conclusion, unripe AP fruit is a promising source of diverse phytochemicals that can be applied in medicinal, nutraceutical, and cosmetic applications as antioxidants and antimicrobials.

Exploring the bioaccessibility and intestinal absorption of major classes of pure phenolic compounds using in vitro simulated gastrointestinal digestion

The bioaccessibility and bioavailability of phenolic compounds (PC) influence directly their role in disease prevention/control. Studies have evaluated this ability through complex plant and food matrices, which may reflect more a synergistic effect of the matrix than the ability of the PCs, hindering their individual exploitation in nutraceutical or pharmaceutical applications. In the present study ten pure PCs representing major classes were evaluated for their bioaccessibility and intestinal absorption in an in vitro simulated gastrointestinal digestion (SGD). This is the first study concerning the bioaccessibility evaluation of pure phloretin, phloroglucinol, naringin, naringenin and daidzein, while no in vitro SGD has been performed before for the other compounds considered here. PCs were analyzed through ultra-high-performance liquid chromatography coupled with diode-array detection and tandem mass spectrometry (UHPLC-DAD-MSn). Most of the compounds remained present along the gastrointestinal tract, and the bioaccessibility was in general higher than 50%, except for quercetin, epigallocatechin gallate, and ellagic acid. All compounds were highly absorbed in the intestine, with phloretin showing the lowest percentage at about 82%. The study findings provide new knowledge on the bioaccessibility and intestinal absorption of different PCs classes.

Revealing the mechanism of post-harvest processing on rose quality based on dynamic changes in water content, enzyme activity, volatile and non-volatile metabolites

Existing studies on post-harvest processing of edible roses have mainly focused on processing techniques and physicochemical properties of the final dried products, with limited studies on how changes in metabolites during processing affect the quality of these products. This study investigated changes in water content and status, enzyme activity, phenolic compounds, and volatile and non-volatile compounds during processing and revealed the mechanisms by which post-harvest processing (drying without blanching (WBD) and drying with blanching (BD)) affects the quality of dried roses by establishing their correlations. Results showed that the blanching reduced the relative content of free water and water activity, thus reducing the subsequent drying time and enzyme activity. The BD method caused higher levels of phenolic compounds than the WBD method in terms of gallic acid, ellagic acid, epicatechin, and quercetin. The OPLS-DA analysis identified 6 differential volatiles out of 72 detected volatiles, contributing to the unique aroma of dried roses by activating olfactory receptors through hydrogen bonding and hydrophobic interactions. 58 differential metabolites were screened from 964 non-volatile metabolites. KEGG pathway analysis revealed that the changes in volatile and non-volatile metabolites induced by different processing methods were due to the effect of blanching on glutathione and fatty acid metabolism. These findings provide a comprehensive understanding of how post-harvest processing affects the quality of dried roses.

Network pharmacology, computational biology integrated surface plasmon resonance technology reveals the mechanism of ellagic acid against rotavirus

The target and mechanism of ellagic acid (EA) against rotavirus (RV) were investigated by network pharmacology, computational biology, and surface plasmon resonance verification. The target of EA was obtained from 11 databases such as HIT and TCMSP, and RV-related targets were obtained from the Gene Cards database. The relevant targets were imported into the Venny platform to draw a Venn diagram, and their intersections were visualized. The protein–protein interaction networks (PPI) were constructed using STRING, DAVID database, and Cytoscape software, and key targets were screened. The target was enriched by Gene Ontology (GO) and KEGG pathway, and the ‘EA anti-RV target-pathway network’ was constructed. Schrodinger Maestro 13.5 software was used for molecular docking to determine the binding free energy and binding mode of ellagic acid and target protein. The Desmond program was used for molecular dynamics simulation. Saturation mutagenesis analysis was performed using Schrodinger's Maestro 13.5 software. Finally, the affinity between ellagic acid and TLR4 protein was investigated by surface plasmon resonance (SPR) experiments. The results of network pharmacological analysis showed that there were 35 intersection proteins, among which Interleukin-1β (IL-1β), Albumin (ALB), Nuclear factor kappa-B1 (NF-κB1), Toll-Like Receptor 4 (TLR4), Tumor necrosis factor alpha (TNF-α), Tumor protein p53 (TP53), Recombinant SMAD family member 3 (SAMD3), Epidermal growth factor (EGF) and Interleukin-4 (IL-4) were potential core targets of EA anti-RV. The GO analysis consists of biological processes (BP), cellular components (CC), and molecular functions (MF). The KEGG pathways with the highest gene count were mainly related to enteritis, cancer, IL-17 signaling pathway, and MAPK signaling pathway. Based on the crystal structure of key targets, the complex structure models of TP53-EA, TLR4-EA, TNF-EA, IL-1β-EA, ALB-EA, NF-κB1-EA, SAMD3-EA, EGF-EA, and IL-4-EA were constructed by molecular docking (XP mode of flexible docking). The MMGBS analysis and molecular dynamics simulation were also studied. The Δaffinity of TP53 was highest in 220 (CYS → TRP), 220 (CYS → TYR), and 220 (CYS → PHE), respectively. The Δaffinity of TLR4 was highest in 136 (THR → TYR), 136 (THR → PHE), and 136 (THR → TRP). The Δaffinity of TNF-α was highest in 150 (VAL → TRP), 18 (ALA → GLU), and 144 (PHE → GLY). SPR results showed that ellagic acid could bind TLR4 protein specifically. TP53, TLR4, and TNF-α are potential targets for EA to exert anti-RV effects, which may ultimately provide theoretical basis and clues for EA to be used as anti-RV drugs by regulating TLR4/NF-κB related pathways.

Evaluation of the Binding Mechanism of Dietary Phytochemical, Ellagic Acid, with Human Transferrin: Spectroscopic, Calorimetric, and Computational Approaches Targeting Neurodegenerative Diseases.

Human transferrin (Htf) is vital in maintaining iron within the brain cells; any disruption results in the development of neurodegenerative diseases (NDs) and other related pathologies, especially Alzheimer's disease (AD). Ellagic acid (EA), a naturally occurring phenolic antioxidant, possesses neuroprotective potential and is present in a broad variety of fruits and vegetables. The current work explores the binding mechanism of dietary polyphenol, EA, with Htf by a combination of experimental and computational approaches. Molecular docking studies unveiled the binding of EA to Htf with good affinity. Molecular dynamic (MD) simulation further provided atomistic details of the binding process, demonstrating a stable Htf-EA complex formation without causing substantial alterations to the protein's conformation. Furthermore, fluorescence binding measurements indicated that EA forms a high-affinity interaction with Htf. Isothermal titration calorimetric measurements advocated the spontaneous nature of binding and also revealed the binding process to be exothermic. In conclusion, the study deciphered the binding mechanism of EA with Htf. The results demonstrated that EA binds with Htf with an excellent affinity spontaneously, thereby laying the groundwork for potential applications of EA in the realm of therapeutics for NDs in the context of iron homeostasis.

Urolithin a Partially Protects against Oxidative Damage Induced for Microcistyn-lr in c6 Cells.

Microcystin-LR (MIC-LR) is a toxin which the mechanism of intoxication involves oxidative stress. Urolithin A (URO-A) is a metabolic product from the colonic fermentation of ellagic acid with antioxidant potential. This study aimed to evaluate the putative protective effect of URO-A against MIC-LR toxicity in C6 cells. C6 cells were incubated with MIC-LR (1 and 10 μM) and/or URO-A (3, 30, 60 and 100 μM) for 24 h. MIC-LR induced reactive species (RS) generation, depletion of total thiol (SH) groups, and survival loss when compared with the control group. Also, at 10 μM, MIC-LR induced CAT activity inhibition. URO-A caused CAT activity inhibition and showed a trend to increase RS generation (60 and 100 μM) per se. URO-A at 3 μM completely attenuated the RS generation and the impairment in SH groups caused by MIC-LR. Our results demonstrated that URO-A might offer a protective effect against toxicity caused by MIC-LR in glial cells by restoring the levels of RS and thiol groups.

Ellagic Acid Co-Administration: A Protective Strategy Against Aging and Dietary-Induced Pheochromocytoma in Rats

Ellagic Acid Co-Administration: A Protective Strategy Against Aging and Dietary-Induced Pheochromocytoma in Rats

Cistus incanus: a natural source of antimicrobial metabolites

The discovery of natural molecules with antimicrobial properties has become an urgent need for the global treatment of bacterium and virus infections. Cistus incanus, a Mediterranean shrub species, represents a valuable source of phytochemicals with an interesting wide-spectrum antimicrobial potential. In this study, we analysed the spectrum of molecules composing a commercial hydroalcoholic extract of C. incanus finding ellagitannins as the most abundant. The effect of the extract and its main constituents (gallic acid, ellagic acid and punicalin) was assessed as co-treatment during viral (HSV-1, HCoV-229E, SARS-CoV-2) and bacterial infection (Staphylococcus aureus and Escherichia coli) of cells and as pre-treatment before virus infections. The results indicated a remarkable antiviral activity of punicalin against SARS-CoV-2 by pre-treating both the viral and the host cells, and a major sensitivity of S. aureus to the C. incanus extract compared to E. coli. The present study highlights broad antimicrobial potential of C. incanus extract.

Argentinian Rose Petals as a Source of Antioxidant and Antimicrobial Compounds.

The total phenolic, flavonoid, and anthocyanin contents were evaluated in 11 cultivars of Argentinian roses of different colors. HPLC-ESI-QTOF/MS was used to identify the components where ellagic and quinic acids, quercetin, and kaempferol glycosylated derivatives were found. The phenolic contents ranged from 78.8 ± 3.2 to 203.4 ± 3.1 mg GAE/g dw, the flavonoid content ranged from 19.1 ± 3.8 to 125.9 ± 6.5 mg QE/g dw, and the anthocyanin content ranged from less than 0.01 to 5.8 ± 0.1 mg CE/g dw. The dark red cultivars exhibited the greatest levels of the analyzed compounds and of the antioxidant activities, even higher than those of certain plants known for their high phenolic contents and antioxidant activity. Moreover, the addition of these extracts decreased the population of L. innocua and P. aeruginosa to undetectable levels 24 h after inoculation. Rose petal extracts, mainly those with a dark red color, can be used as natural additives in food, feed, and cosmetics, as they contain a high proportion of bioactive compounds with antioxidant and antimicrobial effects.