Metal Chelating Research Articles

Methods for negating the impact of zinc contamination to allow characterization of positive allosteric modulators of glycine receptors.

Zinc is a ubiquitous contaminant in many buffers, purified products and common labware that has previously been suggested to impact on the results of functional GlyR studies and may inadvertently cause the effectiveness of some GlyR modulators to be over-estimated. This could greatly impact the assessment of potential drug-candidates and contribute to the reduced effectiveness of compounds that reach clinical stages. This is especially true for GlyR modulators being developed for pain therapeutics due to the changes in spinal zinc concentrations that have been observed during chronic pain conditions. In this study we use two-electrode voltage clamp electrophysiology to evaluate the metal chelators tricine and Ca-EDTA, and show that tricine produces inhibitory effects at GlyRα1 that are not mediated by zinc. We also utilized the zinc insensitive W170S mutation as a tool to validate metal chelators and confirm that zinc contamination has not impacted the examination of lipid modulators previously developed by our lab. This study helps to further develop methods to negate the impact of contaminating zinc in functional studies of GlyRs which should be incorporated into future studies that seek to characterize the activity of novel modulators at GlyRs.

Fabrication, structural elucidation, and DFT calculation of some new hydrophilic metal chelates based on N N′‐(1‐methyl‐2‐oxoindolin‐3‐ylidene)benzohydrazide ligand: Pharmaceutical studies and molecular docking approach

Some novel FeIII, CuII, and PdII chelates incorporating N′‐(1‐methyl‐2‐oxoindolin‐3‐ylidene)benzohydrazide (MIBA) were fabricated. The tested compounds were investigated using thermogravimetric analysis (TGA), CHN, spectra analysis (IR, mass spectra, and NMR), melting point, magnetic moments, molar conductance, ultraviolet–visible spectroscopy, powder X‐ray diffraction, and computational studies. The conductance results showed that the tested FeIII, CuII, and PdII chelates are electrolytes. Magnetic and electronic spectra are applied to deduce the coordinating ability of the tested ligand, and the geometric structure of the studied chelates is found to be octahedral, distorted octahedral, and square planar for FeIII, CuII, and PdII chelates, respectively. The TGA study of these studied complexes displays that the hydrated H2O molecules, acetate, and nitrate are removed in the first and second degradation steps followed directly by degradation of the studied ligand leaving metal oxide as residue. The thermodynamic factors, like ΔS*, ΔH*, E*, A, and ΔG* are evaluated from the TGA curves and explained. The density functional theory (DFT)/B3LYP computation method was applied for the estimation of the molecular electrostatic potential (MEP; highest occupied molecular orbital [HOMO] and lowest unoccupied molecular orbital [LUMO]) energy for the studied compounds. In an in vitro study, the antimicrobial effects of the prepared compounds were screened on various strains of bacteria and fungi. It was found that tested compounds exposed a good biological efficacy through IC50 results close to reference drugs and antitumor potential against (MCF‐7, Hep‐G2, and HC‐T116) cell lines. The data obtained displayed that the studied chelates showed promising antitumor activity. The studied metal chelates were screened for in vitro antioxidant efficacy using DPPH assay. The studied compounds explained dynamic satisfying performance. Also, the crystal structures of breast cancer protein (PDB ID: 3HB5) and Escherichia coli (PDB ID: 2VF5) were performed by molecular docking simulation. Data of docking simulation suggestions are which tested compounds have biological behavior as well as have obvious benefit in the pharmaceutical business.

Synthesis and pharmacological evaluation of novel N-aryl-cinnamoyl-hydrazone hybrids designed as neuroprotective agents for the treatment of Parkinson’s disease

Molecular hybridization between structural fragments from the structures of curcumin (1) and resveratrol (2) was used as a designing tool to generate a new N-acyl-cinnamoyl-hydrazone hybrid molecular architecture. Twenty-eight new compounds were synthesized and evaluated for multifunctional activities related to Parkinson’s disease (PD), including neuroprotection, antioxidant, metal chelating ability, and Keap1/Nrf2 pathway activation. Compounds 3b (PQM-161) and 3e (PQM-164) were highlighted for their significant antioxidant profile, acting directly as induced free radical stabilizers by DPPH and indirectly by modulating intracellular inhibition of t-BOOH-induced ROS formation in neuronal cells. The mechanism of action was determined as a result of Keap1/Nrf2 pathway activation by both compounds and confirmed by different experiments. Furthermore, compound 3e (PQM-164) exhibited a significant effect on the accumulation of α-synuclein and anti-inflammatory activity, leading to an expressive decrease in gene expression of iNOS, IL-1β, and TNF-α. Overall, these results highlighted compound 3e as a promising and innovative multifunctional drug prototype candidate for PD treatment.

TRASUTA: The Effect of the Structural Rigidity of a Mesocyclic AAZTA-like Chelating Agent on the Thermodynamic, Kinetic, and Structural Properties of Some Divalent Metal and Ga3+ Complexes.

Mesocyclic chelating agents such as AAZTA and its derivatives have been recently reported to overcome the relatively low thermodynamic stability of metal complexes of acyclic chelating agents and the slow complexation kinetics of macrocyclic chelating agents. This work reports the preparation of a spirobicyclic hexadentate AAZTA-like chelating agent (TRASUTA) and the investigation of the thermodynamic, kinetic, and structural properties of the corresponding chelates with the PET-relevant Ga3+ and selected metal ions. A combination of analytical techniques allowed identification of a coordination isomerization process, involving the coordinating side arms and the inversion of a nitrogen atom and leading to lower thermodynamic and kinetic inertness with respect to mononuclear mesocyclic analogues. The bicyclic system of TRASUTA retains significant dynamics despite the conformational constraint imposed by the spiro-fusion, resulting in a lower stability of the corresponding metal chelates.

In vitro and In vivo Antioxidant Effect of Mango, Coconut and Cotton Seed Oils on Hydrogen Peroxide- Induced Oxidative Stress in Wistar Rats

This study is aimed at determining the antioxidant activity of Mango kernel oil (MKO), Coconut oil (CCO) and Cotton seed oil (CSO) in vitro and in vivo. Antioxidant parameters demonstrated by five spectrophotometric methods such as: DPPH, FRAP, MCA, HRSA and SRSA was determined in the oils. Superoxide dismutase activity (SOD), catalase activity (CAT) and malondialdehyde (MDA) were evaluated in the serum of the Wistar rats. The antioxidant assay of the oils showed Coconut oil (75.67±0.21 %) was able to neutralize the DPPH radical more than the other oils followed by Cotton seed oil (38.70±0.23 %) and Mango kernel oil (31.56±0.24 %). Coconut oil exhibited the highest FRAP activity at (1.04 mMolFe2+) while the Cotton seed oil displayed significantly lower (P< 0.05) FRAP activity at (0.18±0.00 mMolFe2+). The Metal chelating activity (MCA) of Coconut oil (52.72±0.24 %) was found to be significantly higher than Mango and Cotton seed oils, Superoxide radical scavenging activity showed Coconut oil (62.36±0.01 %) having a relatively high ability to scavenge superoxide radicals better than the other oils with the standard glutathione being significantly higher (81.36±0.07 %). The result of the in vivo study showed the mean values for the SOD of MKO (118.10±5.39 IU/L), CCO (120.53±4.53 IU/L) and CSO (108.80±3.33 IU/L), CAT of MKO (108.93±11.60 IU/L), CCO (96.85±11.69 IU/L) and CSO (88.28±10.66 IU/L) and MDA of MKO (0.25±0.07 mmol/L), CCO (0.24±0.14 mmol/L) and CSO (0.31±0.02 mmol/L). The oils markedly reduced the amount of MDA while significantly increasing the activities of both CAT and SOD content.

Synthesis and bio-activities of bifunctional tetrahydrosalen Cu (II) chelators with potential efficacy in Alzheimer's disease therapy

The dyshomeostasis of metal ions in the brain leads to the accumulation of excess metals in extracellular and inter-neuronal locations and the Amyloid β peptide (Aβ) binds these transition metals, which ultimately cause the Aβ aggregation and severe oxidative stress in the brain. The aggregation of Aβ and oxidative stress are important factors to trigger Alzheimer's disease (AD). Metal chelation therapy is a promising approach to removing metals from Aβ-M species and relieve the oxidative stress. Therefore, 4 tetrahydrosalens containing benzothiazole moiety were designed and synthesized. Their biological activities for Alzheimer's disease therapy in vitro were determined by Turbidity assay, BCA protein assay, MTT assay and fluorescent probe of DCFH-DA. The results were comparing with that of non-specific chelator (cliquinol, CQ) and non-benzothiazole functionalized tetrahydrosalens, the results demonstrated that benzothiazole functionalized chelators had more efficient bio-activities in preventing Cu2+-induced Aβ aggregation, attenuating cytotoxicity mediated by Aβ-Cu2+ species and decrease the level of reactive oxygen species (ROS) in Cu2+-Aβ treated PC12 cells than that of cliquinol and non-benzothiazole functionalized analogues.

Chelation of rare earth metals by perfluorinated β-diketones bearing nitrogen heterocycles rings

Aqueous equilibria of three substituted perfluorinated 1,3-diketones with pyrrole, pyrazole, and pyridine rings have been extensively studied in aqueous solutions. Thermodynamic characteristics of dissociation, protonation, and chelation processes have been investigated by UV–Vis spectroscopy using non-linear regression analysis. Acid-base parameters were discovered in the acidity range from highly acidic media (C(HCl) = 10 M) to alkaline pH region. Dissociation constants (pKa) have been determined in glycine-HCl, phosphate-citrate, and TRIS-HCl buffered media. Protonation activities were studied by the Cox-Yates approach in concentrated hydrochloric acid solutions. First formation constants of ML complex species with trivalent ions of Sc3+, Y3+, La3+, Ce3+, Pr3+, Nd3+, Sm3+, Eu3+, Gd3+, Dy3+, Tb3+, Ho3+, Er3+, Tm3+, Yb3+, and Lu3+ have been obtained in the pH within 3.0–5.6 (I = 0.5 M, NaCl). True stability constants have been calculated using determined acid-base parameters considering side reactions. The “True” formation constants lie from 3.7 to 6.9 logarithmic units and have a linear relationship with the ionic (Coulomb) potential of metals. DFT and TD-DFT simulations have been performed for the modeling of the data obtained.

Catechins counteracted hepatotoxicity induced by cadmium through Keap1-Nrf2 pathway regulation

Catechins, phenolic compounds renowned for their superior antioxidant and metal chelating attributes, are commonly found in foods. Cadmium (Cd) is a highly toxic heavy metal especially detrimental to the liver. However, the potential toxicologic effects of catechins against Cd-induced hepatotoxicity remains poorly studied. To investigate the preventive effects of catechins on Cd exposure, adult C57/BL6J mice were employed, receiving 100 mg/kg body weight (BW) catechins for consecutive 14 days by gavage, followed by acute exposure to 20 mg/kg BW Cd on the final day. Focusing on the liver, our findings demonstrated that catechins effectively alleviated Cd-induced hepatoxicity, including the hepatic Cd accumulation, transaminases levels in serum, inflammation and oxidative stress in the liver. By using brusatol, a Nrf2 inhibitor, the prevention of catechins was reversed, highlighting the crucial key to Kelch-like ECH-associated protein 1 (Keap1)- Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in counteracting Cd-induced hepatoxicity. Our results revealed the beneficial effect of catechins on alleviating Cd-induced hepatotoxicity through the Keap1-Nrf2 pathway, and also provided a novel insight into the beneficial properties of catechins to counteract metal toxicity.

Current understanding of Alzheimer's disease

Worldwide, and disproportionately among the aged, Alzheimer's disease (AD) is a neurological disease that worsens over time and is the main cause of dementia. It begins with a gradual loss of cognitive abilities and memory, progresses to changes in behavior, and culminates in the death of neurons and dementia. A number of promising novel AD therapies, however, are in the works. This article summarizes current theories on the origin of Alzheimer's disease and focuses on recent developments in treatment, including immunotherapy, gene therapy, peptidomimetics, metal chelators.

DETERMINATION OF ANTIOXIDANT ACTIVITY OF HIPPOPHAE RHAMNOIDES L. GROWING IN TURKEY AND INVESTIGATION OF ITS EFFECTS ON THE LIVER TOXICITY IN RATS

Objective: The goal of the present work was to investigate the antioxidant properties of the extracts of Hippophae rhamnoides L. and to determine their effects on liver toxicity in rats. Material and Method: Metal chelation, reducing power and DPPH radical scavenging methods were used in the antioxidant activity analysis of extracts. The total phenolic content was determined using the folin-ciocalteu reagent. Plant extracts were administered orally to the rats at doses of 500 µg/kg for 2 days. Each animal group was composed of six female Albino Wistar rats with an average weight of 250 g. Microscopic examination was carried out to observe any pathological changes in the rat livers. Result and Discussion: Water extract showed the highest radical scavenging activity (48.65%), reducing power (0.291 absorbance at 700 nm) and metal chelating (35.40%) at 1 mg/ml concentration. Histopathological studies showed that especially water extract reduced the severity of CCl4-induced intoxication. Hippophae rhamnoides L. extracts were found to have antioxidant activity, and also Hippophae rhamnoides L. water extract was shown to be particularly effective in preventing liver damage.

Comparative Study of the Phytochemical Profile and Biological Activity of Ajuga reptans L. Leaf and Root Extracts

In this work, the phytochemical composition and the biological activity of the ethanolic extracts obtained from Ajuga reptans L. (Lamiaceae) leaves and roots (growing in Lesser Poland Voivodeship, Poland) were compared. The phytochemical composition of the extracts were determined by the high-performance liquid chromatography with diode-array detection (HPLC–DAD) method. The dominant compounds in both extracts were verbacoside, isoverbacoside, 3,4-dihydroxyphenylacetic acid and rosmarinic acid. The antioxidant capacity of the extracts was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and 2,2’-azobis(3-ethylbenzothiazoline-6-sulfonate (ABTS) tests. The Folin–Ciocalteu assay was used to determine the total polyphenolic content. Additionally, enzyme (tyrosinase, collagenase) inhibition tests and metal chelating ability were studied to assess the anti-aging properties of the extracts. Moreover, the A. reptans extracts’ capacity to absorb the whole range of ultraviolet radiation and high-energy visible (HEV) light was evaluated. The skin irritation test (SIT) EpiDerm was applied to evaluate the safety of the bugle extracts. The noteworthy point is that there is a lack of literature on the assessment of A. reptans root extract activity. Our study is the only one that compares the quantitative composition and biological activity of extracts from the root and leaves of A. reptans. The obtained results indicated that both of the extracts exhibit high antioxidant, chelating and photoprotective activity, but the extract from A. reptans roots showed a higher enzyme inhibition effect for mature skin. The A. reptans root extract, similarly to the leaf extract, could be applied as potentially multi-functional, safe and sensitive cosmetic raw materials, especially in anti-aging and anti-pollution cosmetics.

Photocatalysis-enhanced synthesis and stabilization of silver nanoparticles by methanol-based phytochemicals extract of Trigonella foenum-graecum seeds

Trigonella foenum-graecum is an economically important plant that has significant nutraceutical properties. Various parts of the plant have previously been reported to synthesize metal nanoparticles. However, the seeds of the plant have limited potential to synthesize metal nanoparticles. Green synthesis of silver nanoparticles requires phytochemicals as reducing and metal chelating agents, in addition to the stabilizing agents that play critical role in nanoparticles stabilization. The quantitative analysis of the methanol extract of the seeds suggest that the extract has significant antioxidant activity and reducing potential which is comparable to that of ascorbic acid. Likewise, GCMS data of the extract identified several phytochemical components that have nanoparticles stabilizing potential. Evidently, the extract indeed synthesized silver nanoparticles in dark, albeit in very low quantity. This limitation of low quantity of nanoparticles synthesis was overcome by photocatalysis. The rate of nanoparticles synthesis increased significantly with increase in the intensity of the white light-emitting diode (LED) light. Furthermore, the photocatalytic effect of the white light also has significant impact on the physicochemical characterisation of the nanoparticles. Particle size, nanoparticles yield and elemental analysis demonstrated that the 2000 lumens white LED light is optimum for photocatalysis as compared to the 250 lumens and 825 lumens light. However, the stability of nanoparticles is not influenced by photoirradiation, and is rather controlled by the phytochemical composition of the extract. Methanol extract of the seeds significantly enhanced the stability of the silver nanoparticles irrespective of the light intensities used for photocatalysis.

Comprehensive chemical profiling with UHPLC-MS, in-vitro, in-silico, and in-vivo antidiabetic potential of Typha domingensis Pers; A novel source of bioactive compounds

Aim of studyTypha is one of the valuable plant genera in folklore use in diabetes, and it can be a good source of bioactive chemicals. The current project was planned to investigate the pharmaceutical potential of n-butanol fraction of Typha domingensis Pers. (TDBF), a less explored medicinal plant. Materials and methodsThe phytochemical composition of the TDBF was assessed through a comprehensive analysis, encompassing the quantification of total bioactive contents (including total tannins and HPLC-PDA quantification) and a thorough exploration of secondary metabolites through scanning with UHPLC-MS. The pharmacological assessment included the determination of antioxidant activity (Total Antioxidant Capacity and Metal Chelating Assay), hemolytic potential, in-vitro antidiabetic effects (α-glucosidase and α-amylase inhibition, and antiglycation activity), as well as in-vivo antidiabetic activities. Molecular docking and ADMET studies were also performed for UHPLC-MS identified compounds. ResultsThe TDBF showed 134.76 ± 8.23 mg TAE/g total tannin contents. With HPLC-PDA, p-Hydroxy benzoic acid and p-Coumaric acid were quantified. During UHPLC-MS scanning, a total of five bioactive metabolites were identified in the negative mode, while 54 were detected in the positive mode. The in-vivo assessment of antidiabetic activity revealed a notable reduction in blood glucose levels in diabetic rats following treatment with the extract, demonstrating its efficacy compared to the control groups. Furthermore, the extract exhibited a positive impact on renal and liver function, evidenced by lowered levels of serum urea, ALT, ALP, creatinine, and a decrease in serum cholesterol levels. ConclusionThe results of this study showed that Typha domingensis Pers. possesses a variety of bioactive compounds and demonstrates notable potential in regulating diabetes. The study recommends further investigation into isolating these bioactive phytochemicals for their potential therapeutic applications across various diseases.

Dual-functional lignocellulosic mulch as agricultural plastic alternative for sustained-release of photosensitive pesticide and immobilizing heavy metal ions

The extensive utilization of non-biodegradable plastic agricultural mulch in the past few decades has resulted in severe environmental pollution and a decline in soil fertility. The present study involves the fabrication of environmentally friendly paper-based mulch with dual functionality, incorporating agrochemicals and heavy metal ligands, through a sustainable papermaking/coating technique. The functional paper-based mulch consists of a cellulose fiber web incorporated with Emamectin Benzoate (EB)@ Aminated sodium lignosulfonate (ASL). The spherical microcapsules loaded with the pesticide EB exhibited an optimal core-shell structure for enhanced protection and controlled release of the photosensitizer EB (Sustained release >75 % in 50 h). Meanwhile, the ASL, enriched with metal chelating groups (-COOH, -OH, and -NH2, etc.), served as a stabilizing agent for heavy metal ions, enhancing soil remediation efficiency. The performance of paper-based mulch was enhanced by the application of a hydrophobic layer composed of natural chitosan/carnauba wax, resulting in exceptional characteristics such as superior tensile strength, hydrophobicity, heat insulation, moisture retention, as well as compostability and biodegradability (biodegradation >80 % after 70 days). This study developed a revolutionary lignocellulosic eco-friendly mulch that enables controlled agrochemical release and soil heavy metal remediation, leading to a superior substitute to conventional and non-biodegradable plastic mulch used in agriculture.

X‐ray crystallographic of a novel pyrimidine ligand (LPH) and its metal chelates Cr3+, Ni2+, and Ru3+: A comprehensive study on synthesis, characterization, computational investigations, and biological evaluation toward anticancer and antioxidant

2,4,6‐Triamino‐N‐phenylpyrimidine‐5‐carbothioamide (LPH) was synthesized and extensively characterized. Single crystal X‐ray confirms a monoclinic P21/c space group for LPH. The novel ligand and its chelates of Cr3+, Ni2+, and Ru3+ were studied by elemental analyses, spectral (13C‐,1H‐NMR, UV–visible, IR), magnetic, and thermal measurements. IR spectra indicated that LPH behaves in a bidentate mode through the two NH2 groups of the pyrimidine ring and/or a tetradentate coordination involving the nitrogen atoms of the two NH2 of the pyrimidine ring, NH, and the thioketo (C=S) groups, respectively. By utilizing the Gaussian 09 W program in DFT/B3LYP, we are able to conduct computational estimates of LPH and its metal chelates, yielding insightful data regarding their electronic structure and stability. Biological studies were conducted to assess the isolated compounds' activities against anticancer (MCF‐7), antioxidant (DPPH and ABTS), DNA, and antimicrobial proteins. Molecular docking was employed to investigate the chelates' inhibitory properties, specifically their binding propensity with MCF‐7 cells, revealing possible anticancer action. All the data help to understand LPH and its complexes' production, biological characteristics, and possible therapeutic uses.

Design, structural characterization, DFT, molecular docking, and chemotherapeutic activity of novel platinum(II) and palladium(II) complexes derived from Metformin-based Schiff base

Two novel bidentate Schiff bases ligands derived from Metformin with aldehydic molecules, including o-Ethoxy benzaldehyde (L1) and thiophene-2-carbaldehyde (L2) and Pt(II) and Pd(II) complexes were prepared. Numerous techniques were used to study the ligands and their metal complexes, including mass spectroscopy, IR, UV–Vis, molar conductivity, magnetic moment measurement, 1HNMR, PXRD, and 13CNMR. The preceding two Schiff bases were coordinated to Pd (II) and Pt (II) in the molar ratio of (1:1) (M:L) with the molecular structure [MLCl2]. The chemical quantum characteristics were calculated, and Schiff bases' optimized geometric structures and their complexes were revised theoretically. The MCF-7 breast cancer model was used to test the anticancer effects of metformin Schiff bases and their complexes in vitro. Additionally, using the EGFR tyrosine kinase of the selected proteins, a molecular docking study was carried out to learn more about the docking active site interactions. Ultimately, the conventional DPPH method was used to assess the antioxidant activity of the free ligands and their metal chelates. Pt (II) complexes demonstrated greater free radical scavenging activity than ascorbic acid. Furthermore, Pt (II) complexes showed more effective interactions with the selected mTOR protein, which is assumed to help the COVID-19 virus proliferate. Thus, Pt (II) has a bright future in the realm of chemotherapy.

Targeting Biometals in Alzheimer's Disease with Metal Chelating Agents Including Coumarin Derivatives.

Numerous physiological processes happening in the human body, including cerebral development and function, require the participation of biometal ions such as iron, copper, and zinc. Their dyshomeostasis may, however, contribute to the onset of Alzheimer's disease (AD) and potentially other neurodegenerative diseases. Chelation of biometal ions is therefore atherapeutic strategy against AD. This review provides asurvey of natural and synthetic chelating agents that are or could potentially be used to target the metal hypothesis of AD. Since metal dyshomeostasis is not the only pathological aspect of AD, and the nature of this disorder is very complex and multifactiorial, the most efficient therapeutics should target as many neurotoxic factors as possible. Various coumarin derivatives match this description and apart from being able to chelate metal ions, they exhibit the capacity to inhibit cholinesterases (ChEs) and monoamine oxidase B (MAO-B) while also possessing antioxidant, anti-inflammatory, and numerous other beneficial effects. Compounds based on the coumarin scaffold therefore represent a desirable class of anti-AD therapeutics.

Clioquinol rescues yeast cells from Aβ42 toxicity via the inhibition of oxidative damage.

Alzheimer's disease (AD), the most common form of dementia, has gotten considerable attention. Previous studies have demonstrated that clioquinol (CQ) as a metal chelator is a potential drug for the treatment of AD. However, the mode of action of CQ in AD is still unclear. In our study, the antioxidant effects of CQ on yeast cells expressing Aβ42 were investigated. We found that CQ could reduce Aβ42 toxicity by alleviating reactive oxygen species (ROS) generation and lipid peroxidation level in yeast cells. These alterations were mainly attributable to the increased reduced glutathione (GSH) content and independent of activities of superoxide dismutase (SOD) and/or catalase (CAT). CQ could affect antioxidant enzyme activity by altering the transcription level of related genes. Interestingly, it was noted for the first time that CQ could combine with antioxidant enzymes to reduce their enzymatic activities by molecular docking and circular dichroism spectroscopy. In addition, CQ restored Aβ42-mediated disruption of GSH homeostasis via regulating YAP1 expression to protect cells against oxidative stress. Our findings not only improve the current understanding of the mechanism of CQ as a potential drug for AD treatment but also provide ideas for subsequent drug research and development.

Phenolic and Metabolic Profiles, Antioxidant Activities, Glycemic Control, and Anti-Inflammatory Activity of Three Thai Papaya Cultivar Leaves.

This study thoroughly examined the proximate composition, bioactive composition, and in vitro biological activities of three different cultivars of papaya leaf extracts (PLEs) as potential functional ingredients and nutraceuticals. The dark green leaves of three papaya cultivars, Khaek Dam (KD), Holland (H), and Thai Local (L), were used in this study. The protein content of the leaves ranged from 25.96 to 32.18%, the fat content ranged from 7.34 to 11.66%, the carbohydrate content ranged from 5.80 to 17.91%, the moisture content ranged from 6.02 to 6.49%, the ash content ranged from 11.23 to 12.40%, and the fiber content ranged from 23.24 to 38.48%. The L cultivar possessed significantly higher protein and carbohydrate contents, whereas the H cultivar had the highest ash content (p < 0.05). The total phenolic content (TPC) ranged from 113.94 to 173.69 mg GAE/g extract, with the KD cultivar having the highest TPC (p < 0.05). Several metabolic compounds such as phenolic compounds (particularly kaempferol, isorhamnetin, quercetin, ferulic acid, isoferulic acid, salicylic acid, sinapic acid, syringic acid, and vanillin), terpenoids (such as eucalyptol), glycosides, and indole were identified. The PLE from the KD cultivar had the highest levels of DPPH• inhibition, metal chelation, reducing power, and antidiabetic activity (p < 0.05), suggesting superior biological activity. All three PLEs reduced the proliferation of RAW 264.7 cells in a dose-dependent manner with low nitric oxide formation. These results indicate that the papaya leaf, particularly from the KD cultivar, could be a promising source of functional food ingredients.

The Effect of Two Siderophore-Producing Bacillus Strains on the Growth Promotion of Perennial Ryegrass under Cadmium Stress.

Cadmium (Cd) is a highly toxic and cumulative environmental pollutant. Siderophores are heavy metal chelators with high affinity to heavy metals, such as Cd. Ryegrass (Lolium perenne L.) has a potential remediation capacity for soils contaminated by heavy metals. Consequently, using ryegrass alongside beneficial soil microorganisms that produce siderophores may be an effective means to remediate soils contaminated with Cd. In this study, the Bacillus strains WL1210 and CD303, which were previously isolated from the rhizospheres of Nitraria tangutorum in Wulan and Peganum harmala L. in Dachaidan, Qinghai, China, respectively, both arid and sandy environments, were evaluated for heavy metal pollution mitigation. Our quantitative analyses have discerned that the two bacterial strains possess commendable attributes of phosphorus (P) solubilization and potassium (K) dissolution, coupled with the capacity to produce phytohormones. To assess the heavy metal stress resilience of these strains, they were subjected to a cadmium concentration gradient, revealing their incremental growth despite cadmium presence, indicative of a pronounced tolerance threshold. The subsequent phylogenetic analysis, bolstered by robust genomic data from conserved housekeeping genes, including 16S rDNA, gyr B gene sequencing, as well as dnaK and recA, delineated a species-level phylogenetic tree, thereby confirming the strains as Bacillus atrophaeus. Additionally, we identified the types of iron-carrier-producing strains as catechol (WL1210) and carboxylic acid ferrophilin (CD303). A genomic analysis uncovered functional genes in strain CD303 associated with plant growth and iron carrier biosynthesis, such as fnr and iscA. Ryegrass seed germination assays, alongside morphological and physiological evaluations under diverse heavy metal stress, underscored the strains' potential to enhance ryegrass growth under high cadmium stress when treated with bacterial suspensions. This insight probes the strains' utility in leveraging alpine microbial resources and promoting ryegrass proliferation.