Chelate Iron Ions Research Articles

Highly Stable Alkaline All‐Iron Redox Flow Batteries Enabled by Disulfonated Ligands Chelation

AbstractAlkaline all‐iron flow batteries possess intrinsic safety and low cost, demonstrating great potential for large‐scale and long‐duration energy storage. However, their commercial application is hindered by the issue of capacity decay resulting from the decomposition of iron complexes and ligand crossovers. In this paper, an robust anolyte Fe(TEA‐2S) is reported, which is formed by chelating iron ions with the sulfonate‐enriched ligand (TEA‐2S) in alkaline environment. By skillfully designing the ligands, the binding energy of the iron complexes increases and ligand crossovers are suppressed, making the iron complexes highly stable in the charge–discharge cycles. Alkaline all‐iron flow batteries coupling with Fe(TEA‐2S) and the typical iron‐cyanide catholyte perform a minimal capacity decay rate (0.17% per day and 0.0014% per cycle), maintaining an average coulombic efficiency of close to 99.93% over 2000 cycles along with a high energy efficiency of 83.5% at a current density of 80 mA cm−2. In addition, Fe(TEA‐2S) exhibits high solubility of up to 1.85 м (with a theoretical capacity of up to 49.58 Ah L−1), even at low temperatures as extreme as −30 °C. This work demonstrates a promising pathway toward achieving long‐duration and large‐scale energy storage.

Biological conversion of red garlic (Allium sativum L) protein to bioactive peptides: ACE- DPP-IV inhibitory, and Techno-functional features

This study explores the impact of enzymolysis on the free amino acid content, techno-functional properties, free-radical scavenging, ACE, DPP-IV inhibition, iron-ion chelation and TBARS production in O/W emulsion stabilized with red garlic protein (RGP) and hydrolysates (RGPHs). The research reveals that enzymolysis time and pH significantly influence the amino acid content (antioxidant, hydrophobic, and essential ones), functional and biological quality of RGP/RGPHs. The study demonstrates that enzymolysis positively correlates with solubility (up to 90 %), health-promoting and antioxidant characteristics like DPPH (74.2 %), ABTS (81.3 %), OH (63.4 %), Reducing power (1.1 Abs700), NO (59.5 %), TAA (1.4 Abs695), ACE (71.9 %), DPP-IV (51.5 %) inhibitory, Fe2+ chelating (46.8 %) activity, and leading to reduced water/oil holding capacities, TBARS (from 0.61 to 0.38) value and lipid oxidation. However, extensive enzymatic hydrolysis (over 90 min) reduced emulsion and foaming abilities. On the other hand, the techno-functional properties of RGP and RGPHs exhibited a significant decline near the isoelectric point. This enhancement suggests that RGP could be used as a natural antioxidant with potential health benefits (antihypertensive and antidiabetic) in food and pharmaceutical formulations.

Boosted gas separation performances of polyimide and thermally rearranged membranes by Fe-doping

Herein, p-ferrocenylaniline (CPFEA) is first synthesized from p-nitroaniline and ferrocene as raw materials. Then, a series of Fe-doped rearrangeable polyimide (PI) membranes are prepared by polymerizing 4,4′-(hexafluoroisopropylidene)dithiocarboxylic anhydride (6FDA) and 2,2′-bis(3-amino-4-hydroxyphenyl)hexafluoropropane (6FAP), with CPFEA as an end-capper, followed by thermal imidization and thermal rearrangement (TR) treatment. During the heating process, Fe2+ undergoes a valence state transition, ultimately leading to the coexistence of Fe2+ and Fe3+. The experimental results show that as the CPFEA content increases, the mechanical properties of the Fe-doped PI membranes gradually decrease, but the glass transition temperatures significantly increase due to the chelation of iron ions. In addition, owing to the synergistic effect of Fe2+/Fe3+ on thermal rearrangement reactions and intermolecular interactions, the gas permeabilities and selectivities of the TR composite membranes are greatly improved. Among them, the TR-1.0 %CPFEA sample exhibits the gas permeabilities of 2727, 2442, 407, 107, and 118 Barrer for CO2, H2, O2, N2, and CH4, and the separation performance of CO2/N2 is close to the 2008 Robeson upper limit, the CO2/CH4 exceeds the 2008 Robeson upper limit. When the thermal treatment temperature reaches 500 °C, the gas permeabilities to CO2, H2, O2, N2, and CH4 are respectively boosted to 30591, 13146, 5958, 1714, and 1882 Barrer, and the CO2/CH4 separation performance exceeds the 2019 upper limit. Therefore, this work proposes a feasible method to boost the gas separation performance by end-capping PI backbones with CPFEA, and the Fe-doped TR composite membranes are expected to play a certain role in the environmental and industrial fields.

Amphetamine-like Deferiprone and Clioquinol Derivatives as Iron Chelating Agents.

The accumulation of iron in dopaminergic neurons can cause oxidative stress and dopaminergic neuron degeneration. Iron chelation therapy may reduce dopaminergic neurodegeneration, but chelators should be targeted towards dopaminergic cells. In this work, two series of compounds based on 8-hydroxyquinoline and deferiprone, iron chelators that have amphetamine-like structures, have been designed, synthesized and characterized. Each of these compounds chelated iron ions in aqueous solution. The hydroxyquinoline-based compounds exhibited stronger iron-binding constants than those of the deferiprone derivatives. The hydroxyquinoline-based compounds also exhibited greater free radical scavenging activities compared to the deferiprone derivatives. Molecular dynamics simulations showed that the hydroxyquinoline-based compounds generally bound well within human dopamine transporter cavities. Thus, these compounds are excellent candidates for future exploration as drugs against diseases that are affected by iron-induced dopaminergic neuron damage, such as Parkinson's disease.

Evaluation of Chemical Profile and Biological Properties of Extracts of Different Origanum vulgare Cultivars Growing in Poland.

This research studied the phenolic content compared with the antioxidant properties of various O. vulgare (Lamiaceae) cultivars grown in Poland. The research results in this paper indicate that the dominant ingredient in all oregano cultivars was rosmarinic acid, known for its strong antioxidant properties. The highest amounts of rosmarinic acid (87.16 ± 4.03 mg/g dm) were identified in the O. vulgare spp. hirtum (Link) Ietsw. Other metabolites identified in the studied extracts include luteolin O-di-glucuronide-O-di-pentoside (30.79 ± 0.38 mg/g dm in the 'Aureum' cultivar), 4'-O-glucopyranosyl-3', 4'-dihydroxy benzyl-protocatechuate (19.84 ± 0.60 mg/g dm in the 'Margerita' cultivar), and p-coumaroyl-triacetyl-hexoside (25.44 ± 0.18 mg/g dm in the 'Margerita' cultivar). 'Hot & spicy' and 'Margerita' cultivars were characterized by the highest activity in eliminating OH• and O2•- radicals. Extracts from Greek oregano had the highest ability to scavenge DPPH radicals and chelate iron ions. This research has also provided new evidence that oregano has anti-migratory, cytotoxic properties and influences the viability of gastric cancer cells (the highest cytotoxicity was attributed to the 'Hot & spicy' cultivar, which performed the worst in antioxidant properties tests). Extracts from the tested cultivars at a concentration of 0.625% effectively inhibited the growth of S. aureus and P. aeruginosa bacteria. It seems that the oregano grown in Poland is of good quality and can be successfully grown on a large scale if the appropriate use is found.

Iron ions-sequestrable and antioxidative carbon dot-based nano-formulation with nitric oxide release for Parkinson's disease treatment

Nondestructive penetration of the blood-brain barrier (BBB) to specifically prevent iron deposition and the generation of reactive oxygen species (ROS) shows great potential for treating Parkinson's disease (PD). However, effective agents with distinct mechanisms of action remain scarce. Herein, a N-doping carbon dot (CD) emitting red light was prepared, which can sacrifice ROS and produce nitric oxide (NO) owing to its surface N-involved groups conjugated to the sp2-hybrided π-system. Meanwhile, CD can chelate iron ions, thus depressing the catalytic Fe cycle and *OH detaching to inhibit the Fenton reaction. By modifying lactoferrin (Lf) via polyethylene glycol (PEG), the resulting CD-PEG-Lf (CPL) can nondestructively cross the BBB, targeting the dopaminergic neurons via both NO-mediated reversible BBB opening and Lf receptor-mediated transportation. Accordingly, it can serve as an antioxidant, reducing oxidative stress via its unique iron chelation, free radical sacrificing, and synergy with iron reflux prevention originating from Lf. Thus, it can significantly reduce brain inflammation and improve the behavioral performance of PD mice. Additionally, CPL can image the PD via its red fluorescence. Finally, this platform can be metabolized out of the brain through cerebrospinal fluid circulation without causing obvious side effects, promising a robust treatment for PD.

Phenolic compound profiling and antioxidant potential of different types of Schisandra henryi in vitro cultures.

Schisandra henryi is an endemic species of medicinal potential known from traditional Chinese medicine. As part of this study, a complex biotechnological and phytochemical assessment was conducted on S. henryi with a focus on phenolic compounds and antioxidant profiling. The following in vitro cultures were tested: microshoot agar and callus, microshoot agitated, and suspension, along with the microshoot culture in PlantForm bioreactors. Qualitative profiling was performed by ultra-high-performance liquid chromatography with a photodiode array detector coupled with ion-trap mass spectrophotometry with electrospray ionization and then quantitative analysis by high-performance liquid chromatography with a diode array detector using standards. In the extracts, mainly the compounds from procyanidins were identified as well as phenolic acids (neochlorogenic acid, caffeic acid, protocatechuic acid) and catechin. The highest content of phenolic compounds was found for in vitro agar microshoot culture (max. total content 229.87mg/100g DW) and agitated culture (max. total content 22.82mg/100g DW). The max. TPC measured using the Folin-Ciocalteu assay was equal to 1240.51mg GAE/100g DW (agar microshoot culture). The extracts were evaluated for their antioxidant potential by the DPPH, FRAP, and chelate iron ion assays. The highest potential was indicated for agar microshoot culture (90% of inhibition and 59.31nM/L TEAC, respectively). The research conducted on the polyphenol profiling and antioxidant potential of S. henryi in vitro culture extracts indicates the high therapeutic potential of this species. KEY POINTS: • Different types of S. henryi in vitro cultures were compared for the first time. • The S. henryi in vitro culture strong antioxidant potential was determined for the first time. • The polyphenol profiling of different types of S. henryi in vitro cultures was shown.

Reactive Oxygen Species Activate a Ferritin-Linked TRPV4 Channel under a Static Magnetic Field.

Magnetogenetics has shown great potential for cell function and neuromodulation using heat or force effects under different magnetic fields; however, there is still a contradiction between experimental effects and underlying mechanisms by theoretical computation. In this study, we aimed to investigate the role of reactive oxygen species (ROS) in mechanical force-dependent regulation from a physicochemical perspective. The transient receptor potential vanilloid 4 (TRPV4) cation channels fused to ferritin (T4F) were overexpressed in HEK293T cells and exposed to static magnetic fields (sMF, 1.4-5.0 mT; gradient: 1.62 mT/cm). An elevation of ROS levels was found under sMF in T4F-overexpressing cells, which could lead to lipid oxidation. Compared with the overexpression of TRPV4, ferritin in T4F promoted the generation of ROS under the stimulation of sMF, probably related to the release of iron ions from ferritin. Then, the resulting ROS regulated the opening of the TRPV4 channel, which was attenuated by the direct addition of ROS inhibitors or an iron ion chelator, highlighting a close relationship among iron release, ROS production, and TRPV4 channel activation. Taken together, these findings indicate that the produced ROS under sMF act on the TRPV4 channel, regulating the influx of calcium ions. The study would provide a scientific basis for the application of magnetic regulation in cellular or neural regulation and disease treatment and contribute to the development of the more sensitive regulatory technology.

Efficient Control of Rhizoctonia solani Using Environmentally Friendly pH-Responsive Tannic Acid-Rosin Nano-Microcapsules.

A nanomicrocapsule system was constructed through the polymerization of tannic acid (TA) and emulsifier OP-10 (OP-10), followed by the chelation of iron ions, to develop a safe and effective method for controlling Rhizoctonia solani in agriculture. The encapsulated active component is a rosin-based triazole derivative (RTD) previously synthesized by our research group (RTD@OP10-TA-Fe). The encapsulation efficiency of the nanomicrocapsules is 82.39%, with an effective compound loading capacity of 96.49%. Through the encapsulation of the RTD via nanomicrocapsules, we improved its water solubility, optimized its stability, and increased its adhesion to the leaf surface. Under acidic conditions (pH = 5.0), the release rate of nanomicrocapsules at 96 h is 96.31 ± 0.8%, which is 2.04 times higher than the release rate under normal conditions (pH = 7.0). Additionally, the results of in vitro and in vivo antifungal assays indicate that compared with the original compound, the nanomicrocapsules exhibit superior antifungal activity (EC50 values of RTD and RTD@OP10-TA-Fe are 1.237 and 0.860 mg/L, respectively). The results of field efficacy trials indicate that compared with RTD, RTD@OP10-TA-Fe exhibits a more prolonged period of effectiveness. Even after 3 weeks, the antifungal rate of RTD@OP10-TA-Fe remains at 40%, whereas RTD, owing to degradation, shows an antifungal rate of 11.11% during the same period. Furthermore, safety assessment results indicate that compared with the control, RTD@OP10-TA-Fe has almost no impact on the growth of rice seedlings and exhibits low toxicity to zebrafish. This study provides valuable insights into controlling R. solani and enhancing the compound performance.

Deferasirox exerts anti-epileptic effects by improving brain iron homeostasis via regulation of ITPRIP

Epilepsy constitutes a global health concern, affecting millions of individuals and approximately one-third of patients exhibit drug resistance. Recent investigations have revealed alterations in cerebral iron content in both epilepsy patients and animal models. However, the extant literature lacks a comprehensive exploration into the ramifications of modulating iron homeostasis as an intervention in epilepsy. This study investigated the impact of deferasirox, a iron ion chelator, on epilepsy. This study unequivocally substantiated the antiepileptic efficacy of deferasirox in a kainic acid-induced epilepsy model. Furthermore, deferasirox administration mitigated seizure susceptibility in a pentylenetetrazol-induced kindling model. Conversely, the augmentation of iron levels through supplementation has emerged as a potential exacerbating factor in the precipitating onset of epilepsy. Intriguingly, our investigation revealed a hitherto unreported discovery: ITPRIP was identified as a pivotal modulator of excitatory synaptic transmission, regulating seizures in response to deferasirox treatment. In summary, our findings indicate that deferasirox exerts its antiepileptic effects through the precise targeting of ITPRIP and amelioration of cerebral iron homeostasis, suggesting that deferasirox is a promising and novel therapeutic avenue for interventions in epilepsy.

Carbon quantum dots of ginsenoside Rb1 for application in a mouse model of intracerebral Hemorrhage

After intracerebral hemorrhage (ICH) occurs, the overproduction of reactive oxygen species (ROS) and iron ion overload are the leading causes of secondary damage. Removing excess iron ions and ROS in the meningeal system can effectively alleviate the secondary damage after ICH. This study synthesized ginsenoside Rb1 carbon quantum dots (RBCQDs) using ginsenoside Rb1 and ethylenediamine via a hydrothermal method. RBCQDs exhibit potent capabilities in scavenging ABTS + free radicals and iron ions in solution. After intrathecal injection, the distribution of RBCQDs is predominantly localized in the subarachnoid space. RBCQDs can eliminate ROS and chelate iron ions within the meningeal system. Treatment with RBCQDs significantly improves blood flow in the meningeal system, effectively protecting dying neurons, improving neurological function, and providing a new therapeutic approach for the clinical treatment of ICH.

Improved photothermal properties of a functionalized polydopamine mediated by chelating iron ions

Because of its good photothermal conversion performance, biocompatibility and adhesion of polydopamine nanoparticles (PDA NPs), PDA has been widely used in the biomedical field. However, its hydrophilicity and stability are not good, and the photothermal properties and absorbance of PDA need to be improved. Functionalized polydopamine nanoparticles (NPDA NPs) were prepared by chelating iron ions to solve this problem. The photothermal conversion capacity and light absorption capacity of NPDA were significantly improved. This was attributed to the catalytic effect of iron ions, which can promote the oxidation reaction of PDA and increase the number of oxygen-containing functional groups. The stability of NPDA was significantly enhanced, which was attributed to the fact that iron ions can form coordination bonds with some phenolic hydroxyl groups in PDA. Additionally, there was no significant difference between the photothermal properties of NPDA and drug-loaded NPDA. Two kinds of drug-loaded NPDA NPs, celecoxib loaded NPDA (NPDA@Cel) and desferrioxamine mesylate loaded NPDA (NPDA@DFO), exhibited drug release properties in slightly acidic environment. Near infrared light promoted drug release of NPDA@Cel. This paper provides new ideas for the biomedical applications of PDA nanomaterials.

Chelation of iron(II) ions by ellagitannins—Effects of hexahydroxydiphenoyl and nonahydroxytriphenoyl groups

Tannins represent secondary plant metabolites that are used to control bacterial populations by chelation of essential metal ions. Their presence in food also affects the bioavailability of iron. This study investigates the influence of ellagitannins (vescalin, castalin, vescalagin, castalagin) structure and pH on the stoichiometry and formation constants of ellagitannin-Fe(II) coordination compounds. We demonstrated that ellagitannins are stable for at least one hour at pH values lower than 7.25. The spectra of neutral compounds were measured and explained with the help of TDDFT calculations. Furthermore, the pH-dependence of the ellagitannins UV–Vis spectra was examined to obtain insight into their protolytic equilibrium. Using Job’s method in the pH range 3.50–5.51, the stoichiometry of the formed ellagitannin-Fe(II) ions complexes was determined. A model explaining interactions between ellagitannins and Fe(II) ions, that took into account the protolytic equilibrium of ellagitannins, was fitted globally to all four Job plots, whereby the corresponding formation constants were obtained.

Purification, characterization, and in vitro digestion of novel antioxidant peptides from chicken blood hemoglobin.

The study aimed to purify and characterize antioxidant peptides from chicken blood hemoglobin hydrolysate. The fraction M2 (<3KDa) with the strongest antioxidant activity was isolated by ultrafiltration, and its DPPH (1,1-diphenyl-2-picryl-hydrazyl radical) free radical scavenging rate, ABTS [2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate)] free radical scavenging rate, and iron ion chelation activity were 82.91%, 77.49%, and 80.99%, respectively. After in vitro digestion, the antioxidant capacity of chicken blood hydrolysate was significantly higher than that before digestion (p<0.05). M2 exhibited the strongest antioxidant activity after stomach digestion, with a DPPH radical scavenging rate and iron ion chelating power of 82.91% and 79.61%, respectively. Component A was purified from M2 by Sephadex G-25 gel chromatography. The peptide sequences were identified by LC-MS/MS from fraction A, and four peptides, AEDKKLIQ (944.54Da), APAPAAK (625.36Da), LSDLHAHKL (1033.57Da), and LSNLHAYNL (1044.54Da) were synthesized using the solid-phase peptide method, among which APAPAAK was a novel antioxidant peptide. Molecular docking was used to simulate the binding of these four peptides to the key active site of Keap1 via hydrogen bonding. This study suggests that chicken blood may provide a new natural source of antioxidant peptides.

Towards the synthesis of new sequestring hexadentate bisphosphonic ligands for iron ion chelation

This work presents the design and the synthesis of precursors of hexadentate bisphosphonic ligands able to complex iron cation. This study describes coupling reaction between natural siderophore entity and bisphosphonic acids. These latter have properties of complexing heavy metals. These compounds were obtained from amidation reaction between a protected and activated bisphosphonic compound and serine trilactone. In the intermediate species, all the hydroxyl groups of phosphorus are esterified with ethyl group. The coupling method gave access to triserinelactone-bisphosphonate conjugates in good yields.

A Smooth Muscle Cell-Based Ferroptosis Model to Evaluate Iron-Chelating Molecules for Cardiovascular Disease Treatment.

Dysregulation of iron homeostasis causes iron-mediated cell death, recently described as ferroptosis. Ferroptosis is reported in many chronic diseases, such as hepatic cancer, renal, and cardiovascular diseases (heart failure, atherosclerosis). However, there is a notable scarcity of research studies in the existing literature that explore treatments capable of preventing ferroptosis. Additionally, as far as the author is aware, there is currently no established model for studying ferroptosis within cardiovascular cells, which would be essential for assessing metal-chelating molecules with the potential ability to inhibit ferroptosis and their application in the treatment of cardiovascular diseases. In this study, a smooth muscle cell-based ferroptosis model is developed upon the inhibition of the system Xc- transporter by erastin associated or not with Fe(III) overload, and its rescue upon the introduction of well-known iron chelators, deferoxamine and deferiprone. We showed that erastin alone decreased the intracellular concentration of glutathione (GSH) without affecting peroxidized lipid concentrations. Erastin with ferric citrate was able to decrease intracellular GSH and induce lipid peroxidation after overnight incubation. Only deferiprone was able to rescue the cells from ferroptosis by decreasing lipid peroxidation via iron ion chelation in a 3:1 molar ratio.

Bioinspired phosphorus-free and halogen-free biomass coatings for durable flame retardant modification of regenerated cellulose fibers

Inspired by mussel adhesion and intrinsic flame retardant alginate fibers, a biomass flame retardant (PPCA) containing adhesive catechol and sodium carboxylate structure (-COO−Na+) based on biomass amino acids and protocatechualdehyde was designed to prepare flame retardant Lyocell fibers (Lyocell@PPCA@Na). Furthermore, through the substitution and chelation of metal ions by PPCA in the cellulose molecular chain, flame retardant Lyocell fibers chelating copper and iron ions (Lyocell@PPCA@Cu, Lyocell@PPCA@Fe) were prepared. Compared with the original sample, the peak heat release rate (PHRR) and total heat release (THR) for modified Lyocell fibers were significantly reduced. In addition, the modified sample exhibited a certain flame retardant durability. TG-FTIR analysis showed that the release of flammable gaseous substances was inhibited. The introduction of Schiff bases and aromatic structures in PPCA, as well as the decomposition of carboxylic metal salts were beneficial for the formation of char residue containing metal carbonates and metal oxides to play the condensed phase flame retardant effect. This work develops a new idea for the preparation of eco-friendly flame retardant Lyocell fibers without the traditional flame retardant elements such as P, Cl, and Br.

Modified spectrophotometry for micromolar H2O2 determination in iron-containing solutions with leuco crystal violet under both aerobic and anaerobic conditions.

Accurately quantifying hydrogen peroxide (H2O2) is essential for elucidating its role across diverse environments. Spectrophotometry is widely employed in laboratories for this purpose due to its convenience, cost-effectiveness, and low detection limits for micromolar H2O2 concentrations. However, accurate measurement of H2O2 in iron-containing solutions presents challenges due to the interference of iron ions. In this study, we propose a modified spectrophotometric method for H2O2 determination in iron-containing solutions by adding two types of iron ion chelators and selecting leuco crystal violet (LCV) as a chromogenic reagent due to its stability. By sequentially adding 1,10-phenanthroline and EDTA, and using a phosphate buffer at pH 4.2 to provide the optimal chromogenic pH condition, this modified method effectively mitigates the interference of iron ions in the LCV chromogenic reaction. The applicability of this method under aerobic and anaerobic conditions was confirmed by comparing the experimental results with theoretical simulations. Under optimal chromogenic conditions, this method achieves a detection limit of 300 nM. This improved method allows better detection of H2O2 in iron-containing systems and investigation of its significance in various environmental processes.

Identification of Volatile Molecules and Bioactivity of Gruyt Craft Beer Enriched with Citrus aurantium var. dulcis L. Essential Oil.

In this work, for the first time, a gruyt beer and the same one after the addition of Citrus aurantium essential oil (AEO), were investigated to determine the composition of the volatile fraction. The applied analytical techniques, such as Head Space/Solid Phase Microextraction-Gas Chromatography-Mass Spectrometry (HS/SPME-GC-MS) and Proton Transfer Reaction-Time of Flight-Mass Spectrometer (PTR-ToF-MS), allowed us to identify the content of volatile organic compounds (VOCs). From the comparison between the two beer samples, it showed that the one after the addition of AEO was particularly richened in limonene and a series of minor terpene compounds. AEO was also characterized by GC/MS analysis and the results showed that limonene reached 95%. Confocal microscopy was used to look at riboflavin autofluorescence in yeast cells. It was found that beer with AEO had twice as much fluorescence intensity as the control. A spectrophotometric analysis of total polyphenols, tannins, and flavonoids, and a bioactivity screening, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-Azinobis-(3-Ethylbenzthiazolin-6-Sulfonic Acid) (ABTS) radical scavenger, chelating, reducing, antiglycative ones, were also carried out. Moreover, the tolerability of the tested samples in human H69 cholangiocytes and the cytoprotection towards the tert-butyl hydroperoxide (tBOOH)-induced oxidative damage were evaluated. Under our experimental conditions, the beers were found to be able to scavenge DPPH and ABTS radicals and chelate iron ions, despite weak antiglycative and reducing properties. The tested samples did not affect the viability of H69 cholangiocytes up to the highest concentrations; moreover, no signs of cytoprotection against the damage induced by tBOOH were highlighted. Adding AEO to beer resulted in a moderate enhancement of its DPPH scavenging and chelating abilities, without improvements in the other assays. Conversely, AEO and its major compound limonene were ineffective when assessed at the concentrations added to beer. This evidence suggests that the addition of AEO may enhance the organoleptic features of the beer and slightly potentiate some of its bioactivities.

A new metal ion chelator attenuates human tau accumulation-induced neurodegeneration and memory deficits in mice

Neuronal neurofibrillary tangles containing Tau hyperphosphorylation proteins are a typical pathological marker of Alzheimer's disease (AD). The level of tangles in neurons correlates positively with severe dementia. However, how Tau induces cognitive dysfunction is still unknown, which leads to a lack of effective treatments for AD. Metal ions deposition occurs with tangles in AD brain autopsy. Reduced metal ion can improve the pathology of AD. To explore whether abnormally phosphorylated Tau causes metal ion deposition, we overexpressed human full-length Tau (hTau) in the hippocampal CA3 area of mice and primary cultured hippocampal neurons (CPHN) and found that Tau accumulation induced iron deposition and activated calcineurin (CaN), which dephosphorylates glycogen synthase kinase 3 beta (GSK3β), mediating Tau hyperphosphorylation. Simultaneous activation of CaN dephosphorylates cyclic-AMP response binding protein (CREB), leading to synaptic deficits and memory impairment, as shown in our previous study; this seems to be a vicious cycle exacerbating tauopathy. In the current study, we developed a new metal ion chelator that displayed a significant inhibitory effect on Tau phosphorylation and memory impairment by chelating iron ions in vivo and in vitro. These findings provide new insight into the mechanism of memory impairment induced by Tau accumulation and develop a novel potential treatment for tauopathy in AD.