Metal Ion Chelating Research Articles

Exploration of secondary metabolites from green algae as antimicrobial agents: A comprehensive review

A number of advancements have been made in algal technology in different fields, such as medical, cosmetic, and pharmaceutical. Green algae (Chlorophyta) are a group of photosynthetic organisms which live in both aquatic and terrestrial environments. They are a potential source of bioactive compounds for the treatment and prevention of a wide range of infectious diseases caused by microorganisms. These compounds also possess anti-inflammatory, antioxidant, anticoagulant, antitumor, and immunomodulatory properties. A wide variety of bioactive compounds are produced, including polysaccharides, which exhibit antimicrobial properties capable of interfering with the cell walls, membranes, and nucleic acids of microorganisms. Membrane fluidity, permeability, or integrity can be affected by polyphenols and fatty acids which scavenge free radicals, chelate metal ions, or disrupt enzymes and membranes. Proteins and peptides form pores within the membranes which bind to specific receptors or inhibit enzymes. Adaptation to adverse environmental conditions, such as temperature extremes, photooxidation, salinity, or osmotic stress, results in the formation of bioactive compounds by altering the physiological and biochemical pathways of algae for the maintenance of cellular homeostasis. With changing consumer preferences and an increase in the number of resistant microorganisms, it is critical to seek novel antimicrobial compounds from green algae. The search for novel bioactive compounds with antimicrobial properties from green algae may serve as an alternative in the light of increased drug resistance in microorganisms. However, in vitro and in vivo evaluations of the safety, efficacy, and mechanism of action of the antimicrobial compounds from green algae require more research. Providing an overview of previous endeavours in this emerging field, this review provides perspectives and a summary of the bioactive compounds responsible for the antimicrobial properties of green algal extracts.

Multiple control of azoquinoline based molecular photoswitches.

Multi-addressable molecular switches with high sophistication are creating intensive interest, but are challenging to control. Herein, we incorporated ring-chain dynamic covalent sites into azoquinoline scaffolds for the construction of multi-responsive and multi-state switching systems. The manipulation of ring-chain equilibrium by acid/base and dynamic covalent reactions with primary/secondary amines allowed the regulation of E/Z photoisomerization. Moreover, the carboxyl and quinoline motifs provided recognition handles for the chelation of metal ions and turning off photoswitching, with otherwise inaccessible Z-isomer complexes obtained via the change of stimulation sequence. Particularly, the distinct metal binding behaviors of primary amine and secondary amine products offered a facile way for modulating E/Z switching and dynamic covalent reactivity. As a result, multiple control of azoarene photoswitches was accomplished, including light, pH, metal ions, and amine nucleophiles, with interplay between diverse stimuli further enabling addressable multi-state switching within reaction networks. The underlying structural and mechanistic insights were elucidated, paving the way for the creation of complex switching systems, molecular assemblies, and intelligent materials.

Synthesis and evaluation of butylphthalide-scutellarein hybrids as multifunctional agents for the treatment of Alzheimer's disease

A series of butylphthalide and scutellarein hybrids 3-(alkyl/alkenyl) hydroxyphthalide derivatives were designed, synthesized and evaluated as multifunctional agents against Alzheimer's disease. In vitro bioactivity assays indicated that most of the compounds displayed excellent antioxidant activity and moderate to good inhibition activities of self-induced Aβ1-42 aggregation. Among them, compound 7c was demonstrated as a potential and balanced multifunctional candidate displaying the best inhibitory effects on self- and Cu2+-induced Aβ1–42 aggregation (90.2 % and 35.4 %, respectively) and moderate activity for disaggregation of Aβ1-42 aggregation (42.5 %). In addition, 7c also displayed excellent antioxidant (2.42 Trolox equivalents), metal ions chelating, oxidative stress alleviation, neuroprotective and anti-neuroinflammatory activities. Furthermore, in vivo study demonstrated that 7c could ameliorate the learning and memory impairment induced by sodium nitrite and Aβ1-42 in the step-down passive avoidance test. These balanced multifunctional profiles supporting compound 7c as a novel potential candidate for the treatment of AD.

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.

Extraction and determination of trace Pb(II) and Cd(II) from food and water samples using phosphorylated ceramic column

The consumption of water and food contaminated with potentially toxic metals causes serious health issues. It is beneficial to analyze the level of contamination of such water and food resources before supply for household utility. Here, we electrochemically prepared a porous aluminum oxide (AO) disk and studied for the micro-extraction analysis of Pb(II) and Cd(II) ions in food and water samples. The phosphorylated AO disk was characterized by SEM, EDX and XPS analysis for structural and functional group studies. The phosphorylation significantly increases the chelation of metal ions and enhances the hydrophilicity, leading to significantly shorter analysis time. The prepared material interestingly reduces the spectral interferences by sample cleanup and significantly increases the analyte concentration. Several experimental variables were optimized and the method shows a good detection limit of 0.02 ng mL−1 with RSD 3.52%. The enrichment factor for real samples was found to be 66.6. The presence of co-existing does not much affected and a good tolerance level for other co-existing ions was found for Pb(II) and Cd(II) analyses. The proposed method was validated for its accuracy by standard addition method and by analyzing certified reference materials (NIES 10c and SRM 1572b). The obtained results at 95% confidence level using the Student's t test, are below the critical Student's t value of 4.303, confirming the reliability of procedure. Furthermore, the method shows good precision, with RSD less than 5% for subsequent replicate measurements, reaffirming the consistency and robustness of the method.

Molecular dynamics, molecular docking, DFT, and ADMET investigations of the Co(II), Cu(II), and Zn(II) chelating on the antioxidant activity and SARS-CoV-2 main protease inhibition of quercetin

The natural flavonol quercetin (Q) is found in many vegetables, fruits, and beverages, and it is known as a strong antioxidant. Its metal ion chelation may increase its antioxidant activity. The present study aims to explore the Co(II), Cu(II), and Zn(II) chelating on the antioxidant effectiveness and severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) main protease (Mpro) inhibitory of quercetin using Density-functional theory (DFT), molecular docking, and molecular dynamics simulations (MD). DFT calculations at the B3LYP/LanL2DZ reveal that the high antioxidant activity of the metal-chelated quercetin complexes is mainly returned to their lower ionization potentials (IPs) compared with the one of the free quercetin. Molecular docking of quercetin and its Co(II), Cu(II), and Zn(II) chelates into the active binding sites of peroxiredoxin 5 and SARS-CoV-2 main protease (Mpro) were performed using Lamarckian Genetic Algorithm method. The docked quercetin and its metal chelates fit well into the binding site of the target proteins, and their binding affinity is strongly influenced by the type of the chelated metals Co(II), Cu(II), and Zn(II), and molar ratio metal: ligand, i.e. 1:2 and 2:1. Further, the binding stability of QZn2 and QCu2 in peroxiredoxin 5 and SARS-CoV-2 main protease targets is evaluated using MD simulation conducted for 100 ns simulations at natural room temperature conditions, and the obtained results showed that all chelates remain bound to the ligand binding groove of protein except for 1HD2_QZn2 complex. Finally, the adsorption, distribution, metabolism, excretion, and toxicity (ADMET) and drug-likeness properties of quercetin and cobalt(II)-quercetin (QCo2(II)) were investigated. Communicated by Ramaswamy H. Sarma

Synthesis and application of EDTA grafed metal-organic frameworks (MOFs) and graphene composite for the electrochemical detection of lead(II)

ABSTRACTThe rapid and sensitive detection of heavy metal ion concentrations in water holds significant importance for water resource quality control and protection. In this study, we developed a novel electrochemical sensor utilising a composite material consisting of ethylene diamine tetraacetic acid (EDTA) grafted metal-organic frameworks (MOFs NH2-UiO-66) and graphene to detect Pb2+ in water. The NH2-UiO-66 material exhibited a large specific surface area and porous structure, which was advantageous for the pre-enrichment of the heavy meatal ions. EDTA contained abundant – COOH groups, enabling it to chelate metal ions and increase the reaction sites of redox reactions. The introduction of graphene improved the conductivity of the composite, facilitating electron transfer and enhancing the sensitivity of the electrochemical sensor. Under optimal conditions, the linear range for Pb2+ detection was 0.1 μM–50 μM, and the limit of detection was achieved at 0.052 μM. Furthermore, simultaneous detection of Pb2+ and Cd2+ was successfully accomplished. The fabricated sensor also exhibited excellent selectivity, reproducibility and stability.

Protection of navy-bean bioactive peptides within nanoliposomes: morphological, structural and biological changes

This study aimed to produce bioactive peptides from navy-bean protein with alcalase and pepsin enzymes (30–300 min) and to load them into a nanoliposome system to stabilize and improve their bioavailability. The degree of hydrolysis and biological activities (scavenging of DPPH, OH, and ABTS free radicals, reducing power, and chelating metal ions) of navy-bean protein were affected by the type of enzyme and hydrolysis time. The average particle size (83–116 nm), PDI (0.23–0.39), zeta potential (− 13 to − 20 mV), and encapsulation efficiency (80–91%) of nanoliposomes were influenced by the type and charge of peptides. The storage temperature and the type of loaded peptide greatly affected the physical stability of nanocarriers and maintaining EE during storage. The FTIR results suggested the effect of enzymatic hydrolysis on the secondary structures of protein and the effective placement of peptides inside polar-regions and the phospholipid monolayer membrane. SEM images showed relatively uniform-sized particles with irregular structures, which confirmed the results of DLS. The antioxidant activity of primary peptides affected the free radical scavenging of loaded nanoliposomes. Liposomes loaded with navy-bean peptides can be used as a health-giving formula in enriching all kinds of drinks, desserts, confectionery products, etc.Graphical

Amadori compounds (N-(1-Deoxy-D-fructos-1-yl)-amino acid): The natural transition metal ions (Cu2+, Fe2+, Zn2+) chelators formed during food processing

The Maillard initial products, Amadori compounds (N-(1-Deoxy-D-fructos-1-yl)-amino acid), are considered as the beneficial component with various physiological functions. This study systematically demonstrated that 12 Amadori compounds have effective chelating effect of Cu2+, Fe2+ and Zn2+, and the chelating effect of Cu2+ and Fe2+ is better than that of Zn2+. The chelating strength of Amadori compounds is positively correlated with their concentration. Among them, N-(1-Deoxy-D-fructos-1-yl)-histidine (Fru-His) has the strongest chelating ability. UV spectrum and SEM demonstrated the formation of chelates and the change of surface structure after the chelation reaction. In addition, Amadori compounds have obvious inhibitory effect on the formation of oxidative free radicals caused by metal ions, which can effectively inhibit the oxidative damage of DNA caused by Cu2+ ion and Fenton reaction caused by Fe2+ ion, and reduce Fe3+ ion. Therefore, the Amadori compounds can be applied as a potent metal ion chelator in the development of functional foods.

Bifunctional backbone modified squaramide dipeptides as amyloid beta (Aβ) aggregation inhibitors

Alzheimer's disease (AD) is a devastating neurodegenerative condition with complex pathophysiology. Aggregated amyloid beta (Aβ) peptide plaques and higher concentrations of bio-metals such as copper (Cu), zinc (Zn), and iron (Fe) are the most significant hallmarks of AD observed in the brains of AD patients. Therefore simultaneous inhibition of Aβ peptide aggregation and reduction of metal stress may serve as an effective therapeutic approach for treating Alzheimer's disease. A series of bifunctional dipeptides bearing squaramide backbone were synthesized and investigated for their ability to chelate metal ions and prevent Aβ peptide aggregation. Dipeptides with Valine (V) and Threonine (T) substitutions at the C-terminus exhibited preferential chelation with Cu(II), Zn(II), and Fe(III) metal ions in the presence of other metal ions. They were also found to inhibit the aggregation of Aβ peptide in-vitro. A further molecular dynamics (MD) simulation study demonstrated that these two dipeptides interact with the Aβ peptide in the hydrophobic core (KLVFF) region. Circular dichroism (CD) study revealed slight conformational change in the Aβ peptide upon the interactions with dipeptides. Apart from metal chelation and inhibition of Aβ peptide aggregation, the selected dipeptides were found to possess anti-oxidant properties. Therefore, the squaramide backbone-modified dipeptides may serve as an active bifunctional scaffold towards the development of new chemical entities for the treatment of Alzheimer's disease.

A poly-histidine motif of HOXA1 is involved in regulatory interactions with cysteine-rich proteins

Homopolymeric amino acid repeats are found in about 24 % of human proteins and are over-represented in transcriptions factors and kinases. Although relatively rare, homopolymeric histidine repeats (polyH) are more significantly found in proteins involved in the regulation of embryonic development. To gain a better understanding of the role of polyH in these proteins, we used a bioinformatic approach to search for shared features in the interactomes of polyH-containing proteins in human. Our analysis revealed that polyH protein interactomes are enriched in cysteine-rich proteins and in proteins containing (a) cysteine repeat(s). Focusing on HOXA1, a HOX transcription factor displaying one long polyH motif, we identified that the polyH motif is required for the HOXA1 interaction with such cysteine-rich proteins. We observed a correlation between the length of the polyH repeat and the strength of the HOXA1 interaction with one Cys-rich protein, MDFI. We also found that metal ion chelators disrupt the HOXA1-MDFI interaction supporting that such metal ions are required for the interaction. Furthermore, we identified three polyH interactors which down-regulate the transcriptional activity of HOXA1. Taken together, our data point towards the involvement of polyH and cysteines in regulatory interactions between proteins, notably transcription factors like HOXA1.

A comprehensive evaluation of the effect of key parameters on the performance of DTPA chelating agent in modifying sandstone surface charge

Despite the positive aspects of low salinity water (LSW), this technique is relatively expensive and unavailable in some countries. Furthermore, potential problems associated with LSW such as scale precipitation in carbonate reservoirs and fine migration in sandstone reservoirs raise concerns. Chelating agents have the ability to chelate metal ions from solution, effectively reducing the salinity of seawater (SW) and mimicking the behavior of LSW. However, they mitigate the challenges associated with LSW injection. This study focuses on how the Diethylenetriaminepentaacetic acid (DTPA) chelating agent performs in modifying rock surface charge. The impact of concentration, brine salinity, potential determining ions (PDIs), oil presence, Fe3+ ions, and solution pH on the effectiveness of DTPA in altering rock surface charge was evaluated. Furthermore, wettability alteration and sand pack flooding tests were conducted to study the effect of DTPA on rock wettability and oil recovery. Results of wettability alteration, zeta potential, sand pack flooding experiments and ion concentration analysis are reported in this paper. The results showed that reducing salinity, increasing DTPA concentration, and raising solution pH changed rock wettability from oil-wetness towards water-wetness. The presence or absence of PDIs in the solution did not affect the performance of DTPA. However, by tripling the concentration of these ions in the solution, the performance of DTPA in changing rock surface charge was impaired. Based on the wettability alteration and zeta potential experiments, 5 wt% DTPA was determined as the optimum concentration. Subsequent flooding experiments revealed that injecting 5 wt% DTPA chelating agents into the sandstone sand pack after SW injection increased oil recovery from 48 % to 68.3 %. The analysis of ion concentrations also revealed a significant increase in the amount of calcium ions during the DTPA flooding, indicating the chelation of metal ions from both rock and solution and improving the wettability conditions.

Preparation of mussel-inspired polydopamine-functionalized TEMPO-oxidized cellulose nanofiber-based composite aerogel as reusable adsorbent for water treatment

Water pollution is an ongoing trouble that is of significant urgency to resolve worldwide. However, traditional materials used in the process of water purification are costly and energy intensive. The preparation of low-cost, green and sustainable aerogels with low density, high porosity and high specific surface area (SSA) is a great challenge. In this paper, a mussel-inspired, low-cost, polydopamine (PDA)-functionalized TEMPO-oxidized cellulose nanofiber (TOCNF) PDA/TOCNF composite aerogel has been rationally designed and fabricated with low-density, high porosity and high SSA. The PDA/TOCNF composite aerogel shows low density (18.2 mg/cm3), high porosity (98.7 %), and large surface areas (41.3 m2/g). The resulting PDA/TOCNF composite aerogel could adsorb a maximum of 314.6 mg/g of methylene blue (MB). The recycle experiment for reusing of adsorbent showed that after five consecutive cycles, the removal ability of MB by the PDA/TOCNF composite aerogel still maintained higher than 90 %. In addition, the PDA/TOCNF composite aerogel also had a high adsorption capacity of heavy metal ions, for example, it adsorbs 446.0 mg/g of Cu2+, 222.0 mg/g of Pb2+, 267.0 mg/g of Cd2+, and 600.0 mg/g of Fe3+, respectively. The possible adsorption mechanisms imply that the PDA/TOCNF composite aerogel adsorbs MB due to the synergistic binding interactions, such as electrostatic attraction, π-π stacking interaction, Vander waals force, and hydrogen bonding. Similarly, the PDA/TOCNF composite aerogel adsorbs metal ions due to the electrostatic attraction and chelation of metal ions with the PDA/TOCNF aerogel. Therefore, PDA/TOCNF composite aerogels may have potential applications in wastewater treatment because of their sustainability and low energy consumption.

Antioxidant, Antimicrobial and Spectroscopic Discussion of Guanine Azo Ligand with Cu(II) and Ag (I) Complexes

In this paper, we have provided a very thorough analysis of a new novel chelate metal ion complex of [Cu(II),Ag(I)] prepared via the interaction with the ligand{ 2-amino-8-((4-chloro-3-hydroxyphenyl) diazenyl)azo]guanine} [LAAG], which is synthesized by diazo coupling of the 5-amino-2-chlorophenol with amino acid guanine. The ligand and its complexes are identified by a variety of techniques, like [HNMR, FTIR, and Uv-vis] spectral, thermal analysis (TGA), and element analyses (CHN). The molar ratio was achieved so that the Cu(II) complex has (1:2) (M:L) with octahedral geometry; however, the Ag(I) complex has (1:1) (M:L) with tetrahedral geometry, and the ligand acts as neutral N,N-bidentate; as well as the ligand (LAAG) and its complexes were assessed against the two types of bacteria (Klebsiella pneumonia, Staphylococcus aureus,antifungal (Candida), and antioxidant This study showed that all compounds (the ligand and its complexes) had antimicrobial activity and more biological activity.

Synthesis of Ni2+-functionalized polydopamine magnetic beads for facilitated purification of histidine-tagged proteins

Facilitated purification of proteins, at a low cost and a short time, is one of the key steps in the industrial production of recombinant proteins. In the current study, polydopamine nanoparticles (PDA-NPs) are considered in the synthesis of magnetic beads for purifying recombinant proteins due to advantages such as biocompatibility/ biodegradability, easy synthesis, as well as the ability to directly chelate metal ions. They were synthesized in Tris buffer (pH: 8:5), then chelated with Fe3+(20 mg) and Ni2+ ions at concentrations of 2, 3, 5, and 7 mg/ml. Prepared nanoparticles were characterized through scanning electron microscopy (SEM), ultraviolet-visible spectroscopy (UV-vis), dynamic light scattering (DLS), Inductively Coupled Plasma (ICP), and vibrating sample magnetometer (VSM). The size distribution of the particles was reported in the narrow range of 120–140 nm and 200 to 220 nm by the SEM image and DLS analysis, respectively. The chelation of ions on the surface of the nanoparticle was confirmed by the ICP technique with a magnetization of 35.42 emu/g. The highest adsorption rate of Ni2+ ions to polydopamine was obtained at a ratio of 1.4. The SDS-PAGE and western blot analysis confirmed the purification of eGFP and Hsp40 by PDA/Fe3+/Ni2+ at 26 and 40 kDa compared to the commercial nickel column. Moreover, the concentration of purified eGFP by PDA/Fe3+/Ni2+ was reported 138.83 µg/ml by the fluorescent signals, which is almost equal to or more than the protein purified by commercial Ni-NTA column (108.28 µg/ ml). The stability of PDA/Fe3+/Ni2+ has also been evaluated by ICP-OES for 10 days, and the result suggested that PDA magnetic beads were stable. Therefore, it can be concluded that PDA/Fe3+/Ni2+ have the ability to purify recombinant proteins in one less step and shorter time.

Neuroprotective Potential of Isoquinoline Alkaloids from Glaucium grandiflorum Boiss. and A. Huet subsp. refractum (Nábelek) Mory: Role of NRF2-KEAP1 Pathway

The extracts of Glaucium grandiflorum have been used to treat neurodegenerative diseases. Nonetheless, no former study has investigated whether the alkaloid extracts of G. grandiflorum have antioxidative effects against oxidative stress. The aim of the present study was to determine the antioxidative effects of the alkaloid extracts of G. grandiflorum with a variety of targets and probable mechanisms. First, we used spectrophotometry to investigate alkaloid extracts with respect to their alkaloid amounts. Then, we determined the alkaloid extracts’ impact on thiol/disulfide homeostasis, total oxidant status/total antioxidant status/oxidative stress index, and antioxidant enzyme activities. Finally, the effects of alkaloid extracts on the genes in the NRF2-KEAP1 pathway were determined via qRT-PCR. We conducted molecular docking analyses to determine the potential binding of isoquinoline alkaloids found within the alkaloid extracts with target proteins. We observed the best results from chloroform alkaloid extract and methanol alkaloid extract. Chloroform alkaloid extract was prominent in DPPH radical scavenging and metal ions chelating, and methanol alkaloid extract showed significant hydroxyl radical scavenging, lipid peroxidation, and superoxide anion radical scavenging activity. Alkaloid extract groups substantially increased in total thiol activity, native thiol activity, disulfide activity, total antioxidant status level, antioxidant enzyme levels, and gene expression levels (GCLC, HO-1, NRF2, and NQO1) compared to the H2O2 group. Also, alkaloid extract groups led to a significant drop in total oxidant status level, oxidative stress index level, and KEAP1 gene expression level relative to the H2O2 group. According to our study results, oxidative stress brought about by H2O2 was regulated by alkaloid extracts. As a result, a phytochemical-based therapeutic that regulates H2O2-induced oxidative stress was brought to the neurochemical field.

Pyrolysis process and formation mechanism of water-based ZrC ceramics studied through a combined experimental and theoretical calculational method

ZrC has an important application in the field of supersonic aircraft, hypersonic spacecrafts and rocket engines. Normally, the toxic metal chelators and toxic organic reagents are used to prepare the ZrC ceramic precursors. In this paper, an environmentally friendly water-based ZrC ceramic precursors were synthesized in aqueous solvent via the combination of metal ion chelator and carbon source. Moreover, the water-based ZrC precursor was prepared by Tartaric Acid (TA) system can obtain high-purity ZrC ceramics. The experiment results indicated that the best Zr/C molar ratio in the precursor was 1:4. The synthetic mechanism of ZrC was Zr atoms reacted in situ to form ZrC. In addition, the effect of metal chelator carbon source assisted glucose carbon source on water-based ZrC precursors can provide a certain experimental basis for subsequent research on water-based carbide precursors.

In Vitro Antioxidant and In Vivo Antigenotoxic Features of a Series of 61 Essential Oils and Quantitative Composition-Activity Relationships Modeled through Machine Learning Algorithms.

The antioxidant activity of essential oils (EOs) is an important and frequently studied property, yet it is not sufficiently understood in terms of the contribution of EOs mixtures' constituents and biological properties. In this study, a series of 61 commercial EOs were first evaluated as antioxidants in vitro, following as closely as possible the cellular pathways of reactive oxygen species (ROS) generation. Hence, EOs were assessed for the ability either to chelate metal ions, thus interfering with ROS generation within the respiratory chain, or to neutralize 2,2-diphenyl-1-picrylhydrazyl (DPPH•) and lipid peroxide radicals (LOO•), thereby halting lipid peroxidation, as well as to neutralize 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid cation radicals (ABTS•+) and hydroxyl radicals (OH•), thereby preventing the ROS species from damaging DNA nucleotides. Showing noteworthy potencies to neutralize all of the radicals at the ng/mL level, the active EOs were also characterized as protectors of DNA double strands from damage induced by peroxyl radicals (ROO•), emerging from 2,2'-azobis-2-methyl-propanimidamide (AAPH) as a source, and OH•, indicating some genome protectivity and antigenotoxicity effectiveness in vitro. The chemical compositions of the EOs associated with the obtained activities were then analyzed by means of machine learning (ML) classification algorithms to generate quantitative composition-activity relationships (QCARs) models (models published in the AI4EssOil database available online). The QCARs models enabled us to highlight the key features (EOSs' chemical compounds) for exerting the redox potencies and to define the partial dependencies of the features, viz. percentages in the mixture required to exert a given potency. The ML-based models explained either the positive or negative contribution of the most important chemical components: limonene, linalool, carvacrol, eucalyptol, α-pinene, thymol, caryophyllene, p-cymene, eugenol, and chrysanthone. Finally, the most potent EOs in vitro, Ylang-ylang (Cananga odorata (Lam.)) and Ceylon cinnamon peel (Cinnamomum verum J. Presl), were promptly administered in vivo to evaluate the rescue ability against redox damage caused by CCl4, thereby verifying their antioxidant and antigenotoxic properties either in the liver or in the kidney.

Emodin derivatives as promising multi-aspect intervention agents for amyloid aggregation: molecular docking/dynamics simulation, bioactivities evaluation, and cytoprotection.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with complex pathogenesis. Despite the pathogenesis is unknown, the misfolding and accumulation of β-amyloid (Aβ) peptide play the important role in the occurrence and development of AD. Hence, multi-aspect intervention of the misfolded Aβ peptides aggregation is a promising therapy for AD. In previous work, we obtained the emodin derivatives (a-d) with multifunctional anti-AD activities, including metal ions chelation, cholinesterase inhibition, and hydroxyl/superoxide anion radical elimination. In this work, we predicted the interaction of emodin derivatives (a-d) with Aβ by combining molecular docking simulation and molecular dynamics simulation, and evaluated the ability to intervene with the self-, Cu2+- and AChE-induced Aβ aggregation via in vitro methods. The results indicated that a-d could act as the potent multi-aspect intervention agents for Aβ aggregation. In addition, a-d could effectively eliminate peroxyl radical, had virtually no neurotoxicity, and protect cells from oxidative and Aβ-induced damage. The prediction results of ADMET properties showed that a-d had suitable pharmacokinetic characteristics. It suggested that a-d could act as the promising multi-targeted directed ligands (MTDLs) for AD. These results may provide meaningful information for the development of the potential MTDLs for AD which are modified from natural-origin scaffolds.

Effect of cycloastragenol and punicalagin on Prp(106–126) and Aβ(25–35) oligomerization and fibrillizaton

Numerous neurological disorders, including prion, Parkinson's, and Alzheimer's disease (AD), are identified as being caused by alterations in protein conformation, aggregation, and metal ion dyshomeostasis. Recent years have seen a significant increase in the exploration and study of natural products (NPs) from plant and microbial sources for their therapeutic potential against several diseases, including cancer, diabetes, cardiovascular disease, and neurodegenerative diseases. In this study, we have examined the effect of two NPs, cycloastragenol (CAG) and punicalagin (PCG), on the metal-induced oligomerization and aggregation of Aβ25–35 and PrP106–126 peptides. The peptide aggregation and inhibitory properties of both NPs were examined by the thioflavin-T (ThT) assay, MALDI-TOF, circular dichroism (CD) spectroscopy, and transmission electron microscopy (TEM). Among the two NPs, PCG significantly binds to the peptides, chelates metal ions (Cu2+ and Zn2+), inhibits peptide aggregation, substantially reduces oxidative stress, and controls the production of reactive oxygen species (ROS). Both NPs exhibited low cytotoxicity and prominently mitigated peptide-mediated cell cytotoxicity in hippocampal neuronal HT-22 cells by covalent bonding and hydrophobic interactions.