Role of Flavonoids in Management of Various Biological Targets in Alzheimer's Disease: Evidence from Preclinical to Clinical Studies.

More than 10 million people worldwide have Alzheimer's disease (AD), a degenerative neurological illness and the most prevalent form of dementia. AD's progression in memory loss, cognitive deterioration, and behavioral changes are all symptoms. Amyloid-beta 42 (Aß42), the hyperphosphorylated forms of microtubule-associated tau protein, and other cellular and systemic alterations are all factors that contribute to cognitive decline in AD. Rather than delivering a possible cure, present therapy strategies focus on reducing disease symptoms. It has long been suggested that various naturally occurring small molecules (plant extract products and microbiological isolates, for example) could be beneficial in preventing or treating disease. Small compounds, such as flavonoids, have attracted much interest recently due to their potential to alleviate cellular stress. Flavonoids have been proven helpful in various ways, including antioxidants, anti-inflammatory agents, and anti-apoptotic agents, but their mechanism remains unknown. The flavonoid therapy of Alzheimer's disease focuses on this review, which includes a comprehensive literature analysis.

Process Optimization for Development of Guar Gum-Based Biodegradable Hydrogel Film Using Response Surface Methodology.

In the current study, a guar-gum-based biodegradable hydrogel film was prepared using an initiator (potassium persulfate), crosslinker (N-N methyl bis acrylamide), and plasticizer (glycerol) for packaging of fruits and vegetables. The effect of independent variables (initiator, crosslinker, and plasticizer) on the biodegradation (% wt. loss), color difference (ΔE), hardness (N), swelling index (%), and transparency (%) of the film was studied using Box-Behnken design, random surface methodology (RSM). The results showed significant effects on all the abovementioned parameters, and it was observed that the developed model was accurate, with a prediction error of only -3.19 to 2.99%. The optimized formulation for the preparation of hydrogel film was 0.15% initiator, 0.02% crosslinker, and 2.88% plasticizer exhibiting satisfactory biodegradability, color difference, hardness, swelling index, and transparency. Results showed that a guar-gum-based biodegradable hydrogel film has adequate physical, optical, and biodegradable properties and can be successfully utilized in the food packaging industry.

Advances and applications of monoolein as a novel nanomaterial in mitigating chronic lung diseases.

Chronic lung diseases such as asthma, chronic obstructive pulmonary disease, lung cancer, and the recently emerged COVID-19, are a huge threat to human health, and among the leading causes of global morbidity and mortality every year. Despite availability of various conventional therapeutics, many patients remain poorly controlled and have a poor quality of life. Furthermore, the treatment and diagnosis of these diseases are becoming increasingly challenging. In the recent years, the application of nanomedicine has become increasingly popular as a novel strategy for diagnosis, treatment, prevention, as well as follow-up of chronic lung diseases. This is attributed to the ability of nanoscale drug carriers to achieve targeted delivery of therapeutic moieties with specificity to diseased site within the lung, thereby enhancing therapeutic outcomes of conventional therapies whilst minimizing the risks of adverse reactions. For this instance, monoolein is a polar lipid nanomaterial best known for its versatility, thermodynamic stability, biocompatibility, and biodegradability. As such, it is commonly employed in liquid crystalline systems for various drug delivery applications. In this review, we present the applications of monoolein as a novel nanomaterial-based strategy for targeted drug delivery with the potential to revolutionize therapeutic approaches in chronic lung diseases.

Solanum tuberosum Leaf Extract Templated Synthesis of Co3O4 Nanoparticles for Electrochemical Sensor and Antibacterial Applications.

Green synthesis of metal oxide nanoparticles (NPs) is a viable alternative methodology because of cost-effective and availability of environmentally friendly templates for desired application, which has attracted the attention of researchers in recent years. In the present study, Co3O4 NPs were synthesized in various volume ratios in the presence of Solanum tuberosum leaf extract as a template. The synthesized Co3O4 NPs were characterized by X-ray diffraction (XRD), scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX), transmission electron microscopy (TEM), high resolution transmission electron microscopy (HRTEM), surface area electron diffraction (SAED), UV-Vis diffuse reflectance spectroscopy (UV-DRS), and Fourier transform infrared (FTIR) spectroscopy. XRD analysis found that the average crystalline sizes for the 1 : 2, 1 : 1, and 2 : 1 volume ratios was 25.83, 21.05, and 27.98 nm, respectively. SEM-EDX and TEM analyses suggest that the green-synthesized Co3O4 NPs are spherical in shape without the presence of impurities. The band gap E g values of the 1 : 2, 1 : 1, and 2 : 1 volume ratios of Co3O4 NPs were found to be 1.83, 1.77, and 2.19 eV, respectively. FTIR analysis confirmed the presence of various bioactive ingredients within the leaf extract of Solanum tuberosum. Co3O4 NPs-modified electrodes showed better sensing capability towards ascorbic acid and citric acid due to enhanced electron transfer kinetics. Among three volume ratios (1 : 2, 1 : 1, and 2 : 1) of Co3O4 nanoelectrodes, 1 : 1 and 2 : 1 were identified as the best performing nanoelectrodes. This is possibly due to the high catalytic behavior and the more homogenized surface structure. Co3O4 (1 : 2) nanodrug showed the enhanced antibacterial activity (16 mm) towards S. aureus which is attributed to the formation of enhanced reactive oxygen species (ROS).

Adsorptive removal of Rhodamine B dye from aqueous solution by using graphene-based nickel nanocomposite.

In this work, reduced graphene oxide-nickel (RGO-Ni) nanocomposite is synthesized. X-ray diffraction (XRD), scanning electron microscopy (SEM) and SEM-EDS (Energy Dispersive X-Ray Spectroscopy) are used to study the crystalline nature, morphology and elemental composition of the RGO-Ni nanocomposite, respectively. As synthesized RGO-Ni nanocomposite is used to develop selective adsorptive removal of Rhodamine B (RhB) dye from the aqueous solution. The experiments have been performed to investigate RhB uptake via RGO-Ni nanocomposites which include, contact time (60 min), initial dye concentration (50 mg/100 ml), adsorbent dosage (0.5 mg) and pH 8 of dye solution. The equilibrium concentration is determined by using different models namely, Freundlich, Langmuir and Tempkin. Langmuir isotherm has been fitted well. Langmuir and Tempkin equations are determined to have good agreement with the correlation coefficient data. The kinetic study concluded that RhB dye adsorption follows with the pseudo-second-order kinetic model. Further, adsorption mechanism of RGO-Ni is proposed which involves three steps. The synthesized adsorbent is compared with the other adsorbents in the literature and indicates that RGO-Ni nanocomposite used in this study shown better results for a particular adsorption capacity than polymeric, natural and synthetic bioadsorbents. The regeneration and reusability experiments suggest RGO-Ni nanocomposite can be used for many numbers of times for purification/adsorption.

Photocatalytic degradation of organic dyes: Pd-γ-Al2O3 and PdO-γ-Al2O3 as potential photocatalysts.

This work describes photocatalytic application of γ-alumina (γ-Al2O3) surface-anchored palladium and palladium oxide nanoparticles (Pd-γ-Al2O3 and PdO-γ-Al2O3 NPs) synthesized by a novel co-precipitation technique. The palladium(0) NPs (Pd-γ-Al2O3) were formed by calcination of the sample in inert medium, whereas PdO NPs (PdO-γ-Al2O3) were obtained by calcination of the sample in atmospheric oxygen. As-synthesized Pd-γ-Al2O3 and PdO-γ-Al2O3 NPs are characterized by X-ray diffraction, Fourier transform-infrared spectroscopy, field emission scanning electron microscopy and photoluminescence (PL) spectra. The PL spectra of Pd-γ-Al2O3 and PdO-γ-Al2O3 NPs display visible-light emissions from 450 to 500 nm at room temperature. This work aims to study the photocatalytic degradation of organic dye pollutants, including bromocresol green (BCG), bromothymol blue, methylene blue and methyl orange using Pd-γ-Al2O3 and PdO-γ-Al2O3 NPs as potential photocatalysts. Experimental parameters, including the admitting concentration of the organic dye solution, Pd-γ-Al2O3 and PdO-γ-Al2O3 photocatalyst dosage, and pH, were varied to ascertain favorable conditions for photocatalytic degradation. The results indicate that the organic dye BCG is completely (100%) degraded in aqueous solution under ultraviolet light, compared with the other organic dyes. Furthermore, Pd-γ-Al2O3 NPs showed better photocatalytic performance than PdO-γ-Al2O3 NPs. The possible photocatalytic degradation mechanism of the organic dyes by Pd-γ-Al2O3 and PdO-γ-Al2O3 photocatalysts is proposed. The studies reveal that Pd and PdO NPs anchored on the γ-Al2O3 surface are promising and effective catalysts for photocatalytic degradation of organic dyes.

Stability-Indicating RP-HPLC Method for Simultaneous Estimation of Enrofloxacin and Its Degradation Products in Tablet Dosage Forms.

The present work was the development of a simple, efficient, and reproducible stability-indicating reverse-phase high performance liquid chromatographic (RP-HPLC) method for simultaneous determination enrofloxacin (EFX) and its degradation products including ethylenediamine impurity, desfluoro impurity, ciprofloxacin impurity, chloro impurity, fluoroquinolonic acid impurity, and decarboxylated impurity in tablet dosage forms. The separation of EFX and its degradation products in tablets was carried out on Kromasil C-18 (250 × 4.6 mm, 5 µm) column using 0.1% (v/v) TEA in 10 mM KH2PO4 (pH 2.5) buffer and methanol by linear gradient program. Flow rate was 1.0 mL min(-1) with a column temperature of 35°C and detection wavelength was carried out at 278 nm and 254 nm. The forced degradation studies were performed on EFX tablets under acidic, basic, oxidation, thermal, humidity, and photolytic conditions. The degraded products were well resolved from the main active drug and also from known impurities within 65 minutes. The method was validated in terms of specificity, linearity, LOD, LOQ, accuracy, precision, and robustness as per ICH guidelines. The results obtained from the validation experiments prove that the developed method is a stability-indicating method and suitable for routine analysis.

Controllable synthesis of thiol-capped CdTe nanoparticles for optical sensing of triethylenetetramine dihydrochloride.

Highly luminescent CdTe quantum dots (QDs) were synthesized through a co-precipitation route in aqueous salt solutions using different thiols as stabilizers. The synthetic procedure was simple, efficient, and stable. It could also allow controlling the emission wavelength by varying the experimental conditions such as reaction time and pH values. The strong luminescence of the QDs was observed under UV-excitation and emission colors could be adjusted. The interaction between CdTe QDs and triethylenetetramine dihydrochloride (TETA) which is a candidate treatment for diabetic cardiovascular complication was investigated by fluorescence spectroscopy. Based on the quenching effect on CdTe photoluminescence intensity by TETA, a simple assay system for analyzing the content of TETA in aqueous samples was developed. The linearity was maintained in the range of 0.2 µM to 1.2 µM (R2 = 0.994) with a limit of detection (LOD; S/N = 3) at 28 nM. The results showed that CdTe QDs capped with diverse thiols has a potential for the quantitative analysis of TETA in urine samples.

Chiral zirconia magnetic microspheres as a new recyclable selector for the discrimination of racemic drugs.

Separation of enantiomers of a chiral compound is one of the most interesting and challenging tasks because of their identical physical and chemical properties. Magnetic materials possessing chiral functionality on their surface can not only exhibit magnetic properties but also recognize chirality. Fe3O4@ZrO2 core-shell nano-materials have not been reported previously for chiral separation of racemates. Zirconia has been shown to be the most stable oxide mechanically, thermally and chemically, and shows better physical and chemical properties among inorganic metal oxides. The present work explores core-shell microspheres consisting of a Fe3O4 magnetic core covered by a zirconia shell (Fe3O4@ZrO2) which are immobilized with cellulose tris(3,5-dimethylphenylcarbamate) to get chiral zirconia magnetic microspheres (CZMMs). As-synthesized CZMMs have been applied for the separation of racemic chiral drugs and the results indicate the CZMMs are potential chiral nanomaterials for enantioseparations. Most importantly the synthesized CZMMs have shown an excellent recyclability and can be used for further chiral separations of different kinds of racemates.

Chiral separation of basic compounds on a cellulose 3,5-dimethylphenylcarbamate-coated zirconia monolithin basic eluents by capillary electrochromatography.

Porous zirconia monolith (ZM) modified with cellulose 3,5-dimethylphenylcarbamate (CDMPC) was used as chiral stationary phase to separate basic chiral compounds in capillary electrochromatography. The electroosmotic flow behavior of bare and CDMPC-modified zirconia monolithic (CDMPC-ZM) column was studied in ACN/phosphate buffer eluents of pH ranging from 2 to 12. The CDMPC-ZM column was evaluated by investigating the influences of pH, the type and composition of organic modifier of the eluent on enantioseparation. CEC separations at pH 9 provided the best resolutions for the analytes studied, which are better than those observed on CDMPC-modified silica monolithic columns under similar chromatographic conditions. No appreciable decline in retention and resolution factors after over 200 injections, and run-to-run and day-to-day repeatabilities of the column of less than 3% indicate the stability of the zirconia monolithic column in basic media.

Fast separations of chiral ß-blockers on a cellulose tris(3,5-dimethylphenylcarbamate)-coated zirconia monolithic column by capillary electrochromatography.

Cellulose tris(3,5-dimethylphenylcarbamate) (CDMPC) is an excellent chiral selector for enantioseparation of a wide variety of chiral compounds. The monolithic chiral columns are becoming popular in liquid chromatography and capillary electrochromatography. In this work, we present the fast separation of chiral ß-blockers on a CDMPC-modified zirconia monolithic column by capillary electrochromatography (CEC). The porous zirconia monolithic capillary column was prepared by using the sol-gel technology and then zirconia surface modified with CDMPC. The enantioseparations were performed in reversed-phase (RP) eluents of a phosphate solution (pH 4.4) modified with acetonitrile or alcohol. The enantioseparations of a set of eight chiral ß-blockers were achieved in less than one minute. Influences of the applied voltage, column temperature, concentration of acetonitrile and the type of alcohol as the organic modifier in the mobile phase, and sample injection time on enantioseparation were investigated. CEC separations at the applied voltage of 10 kV and 15 °C in the ACN-modified mobile phase provided the best resolutions for the analytes studied. Run-to-run and day-to-day repeatabilities of the column in the RP-CEC separation were less than 1 and 2%, respectively.

Azithromycin as a new chiral selector in capillary electrophoresis.

In capillary electrophoresis (CE), separation of enantiomers of a chiral compound can be achieved through the chiral interactions and/or complex formation between the chiral selector and the enantiomeric analytes on leaving their diastereomeric forms with different stability constants and hence different mobilities. A great number of chiral selectors have been employed in CE and among them macrocyclic antibiotics exhibited excellent enantioselective properties towards a wide number of racemic compounds. The use of azithromycin (AZM) as a chiral selector has not been reported previously. This work reports the use of AZM as a chiral selector for the enantiomeric separations of five chiral drugs and one amino acid (tryptophan) in CE. The enantioseparation is carried out using polar organic mixtures of acetonitrile (ACN), methanol (MeOH), acetic acid and triethylamine as run buffer. The influences of the chiral selector concentration, ACN/MeOH ratio, applied voltage and capillary temperature on enantioseparation are investigated. The results show that AZM is a viable chiral selector in CE for the enantioseparation of the type of chiral drugs investigated.

Enantioseparation on cellulose dimethylphenylcarbamate-modified zirconia monolithic columns by reversed-phase capillary electrochromatography.

This work reports the preparation of monolithic zirconia chiral columns for separation of enantiomeric compounds by capillary electrochromatography (CEC). Using sol-gel technology, a porous monolith having interconnected globular-like structure with through-pores is synthesized in the capillary column as a first step in the synthesis of monolithic zirconia chiral capillary columns. In the second step, the surface of the monolith is modified by coating with cellulose tris(3,5-dimethylphenylcarbamate) (CDMPC) as the chiral stationary phase to obtain a chiral column (CDMPCZM). The process of the preparation of the zirconia monolithic capillary column was investigated by varying the concentrations of the components of the sol solution including polyethylene glycol, water and acetic acid. CDMPCZM is mechanically stable and no bubble formation was detected with the applied current of up to 30 microA. The enantioseparation behavior of the CDMPCZM columns was investigated by separating a set of 10 representative chiral compounds by varying the applied voltage and pH and organic composition of the aqueous organic mobile phases.

Isomeric discrimination and quantification of thyroid hormones, T3 and rT3, by the single ratio kinetic method using electrospray ionization mass spectrometry.

The single ratio kinetic method is applied to the discrimination and quantification of the thyroid hormone isomers, 3,5,3'-triiodothyronine and 3,3',5'-triiodothyronine, in the gas phase, based on the kinetics of the competitive unimolecular dissociations of singly charged transition-metal ion-bound trimeric complexes [M(II)(A)(ref*)(2)-H](+) (M(II) = divalent transition-metal ion; A = T(3) or rT(3); ref* = reference ligand). The trimeric complex ions are generated using electrospray ionization mass spectrometry and the ions undergo collisional activation to realize isomeric discrimination from the branching ratio of the two fragment pathways that form the dimeric complexes [M(II)(A)(ref*)-H](+) and [M(II)(ref*)(2)-H](+). The ratio of the individual branching ratios for the two isomers R(iso) is found strongly dependent on the references and the metal ions. Various sets are tried by choosing the reference from amino acids, substituted amino acids, and dipeptides in combination with the central metal ion chosen from five transition-metal ions (Co(II), Cu(II), Mn(II), Ni(II), and Zn(II)) for the complexes in this experiment. The results are compared in terms of the isomeric discrimination for the T(3)/rT(3) pair. Calibration curves are constructed by relating the ratio of the branching ratios against the isomeric composition of their mixture to allow rapid quantitative isomer analysis of the sample pair. Furthermore, the instrument-dependence of this method is investigated by comparing the two sets of results, one obtained from a quadrupole ion trap mass spectrometer and the other from a quadrupole time-of-flight mass spectrometer.

Enhanced detection and structural characterization of flavonoids by complexation with N,O-bis(trimethysilyl)trifluoroacetamide using electrospray ionization mass spectrometry.

Many natural products contain flavonoids that display biological effects when ingested by humans and animals. Flavonoids have received a great deal of research interest, especially for possible cancer and heart disease-preventive properties. The content and the quality of each flavonoid may be a key to their biological effects. The recent development of electrospray ionization mass spectrometry (ESI-MS/MS) has made it possible to use it to study molecular interactions. In the present work, we investigated the derivatization procedures for three flavonoids (chrysin, genistein, and luteolin) by using ESI-MS/MS. Each flavonoid and the derivatization reagent, N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA), are mixed using acetonitrile and the mixture is introduced through an electrospray needle. The signal intensities for the derivative ions significantly increased, almost two or three orders of magnitude increased as compared to those for the protonated molecular ions of the flavonoids. Mass spectra of trimethylsilyl derivatives are fragmented at a fixed pattern by collision induced dissociation to obtain the structural relevance of the derivative flavonoids. Further fragmentation studies have been performed and results are discussed in detail. The results in the positive mode detection show that better high intensity data and more simplification of peaks appeared than that for the underivatized cases.

Interaction of glutathione and sodium selenite in vitro investigated by electrospray ionization tandem mass spectrometry.

Selenite has been found to be an active catalyst for the oxidation of sulphhydryl compounds, such as glutathione (GSH). Considering the biological importance of GSH oxidation and the implication of sulphhydryl compounds in selenium poisoning and other biological activities, more information on selenite oxidation of GSH in enzyme-free conditions is desirable. Herein, we describe glutathione and sodium selenite simply mixed in aqueous solutions. The interaction products and transient intermediate are identified and characterized using electrospray ionization (ESI) tandem mass spectrometry. In the first step, GSH directly reacts to form diglutathione (GSSG) and unstable selenodiglutathione (GS-Se-SG). Then selenodiglutathione further reacted with remaining GSH to form diglutathione and elemental selenium, Se(0). As the amount of GSSG significantly increased or acidity of the solution increased, the redox potential of glutathione [E(0')(GSSG/2GSH) approximately -250 mV (NHE)] significantly shifted to the positive direction. This makes the GSSG react with elemental selenium formed in the solution, which can be demonstrated by another unstable intermediate ion identified at m/z 418 by mass spectrometry with the elemental composition of [GSS-Se](-). The reaction mechanism between GSH and sodium selenite has been proposed according to the ESI-MS, NMR and UV-vis spectrometric measurements.

Determination of enantiomeric compositions of DOPA by tandem mass spectrometry using the kinetic method with fixed ligands.

A fixed ligand (FL) version of the kinetic method was applied to rapid, simple, and accurate chiral analysis of DOPA, which is an important drug used for treatment of Parkinson's disease. Singly charged clusters containing the transition metal ion Cu(II), pyridyl ligands which serve as a fixed ligand, some amino acid as a reference, and the analyte DOPA were generated by electrospray ionization. The cluster ion of interest was mass-selected, and the kinetics of its competitive unimolecular dissociations was investigated in an ion trap mass spectrometer. The chiral selectivity (R(chiral)), the ratio of the two fragment ion abundances when the cluster contains one pure enantiomer of the analyte expressed relative to that for the other enantiomer, varies with fixed ligands, references, and transition metals. Chiral discrimination was optimized in 1,10-phenanthroline as a FL, L-Phe and L-Pro as a reference, and Cu(II) as a central metal ion. Quantitative determinations of the enantiomeric composition of DOPA were achieved using two-point calibration curves. The linear relationship between the logarithm of the fragment ion abundance ratio (ln R) and enantiomeric compositions (ee%) of the DOPA allows the determination of the chiral purity of enantiomeric mixtures.