Selective production of phenolic monomer via catalytic depolymerization of lignin over cobalt-nickel-zirconium dioxide catalyst.

The utilization of lignin, an abundant and renewable bio-aromatic source, is of significant importance. In this study, lignin oxidation was examined at different temperatures with zirconium oxide (ZrO2)-supported nickel (Ni), cobalt (Co) and bimetallic Ni-Co metal catalysts under different solvents and oxygen pressure. Non-catalytic oxidation reaction produced maximum bio-oil (35.3 wt%), while catalytic oxidation significantly increased the bio-oil yield. The bimetallic catalyst Ni-Co/ZrO2 produced the highest bio-oil yield (67.4 wt%) compared to the monometallic catalyst Ni/ZrO2 (59.3 wt%) and Co/ZrO2 (54.0 wt%). The selectively higher percentage of vanillin, 2-methoxy phenol, acetovanillone, acetosyringone and vanillic acid compounds are found in the catalytic bio-oil. Moreover, it has been observed that the bimetallic Co-Ni/ZrO2 produced a higher amount of vanillin (43.7% and 13.30 wt%) compound. These results demonstrate that the bimetallic Ni-Co/ZrO2 catalyst promotes the selective cleavage of the ether ß-O-4 bond in lignin, leading to a higher yield of phenolic monomer compounds.

Optimizing the Vanillin-Acid Sulfuric Method to Total Saponin Content in Leaves of Yerba Mate Clones.

Yerba mate (Ilex paraguariensis) is a forest species consumed in the form of non-alcoholic beverages in South America, with applications in foods, cosmetics, and pharmaceutical industries. The species leaves are globally recognized for their important bioactive compounds, including, saponins. We adjusted the vanillin-acid sulfuric method for determining spectrophotometrically the total saponin in yerba mate leaves. Seeking to maximize the extraction of saponins from leaves, a Doehlert design combined with Response Surface Methodology (RSM) was used, considering ethanol:water ratios and ultrasound times. In addition, the same methodology was used for the analysis of times and temperatures in the vanillin-sulfuric acid reaction heating. The contents of total saponin in mature leaves were compared in four yerba mate clones. The extraction was maximized using 40 % ethanol:60 % water and 60 minutes of ultrasound assisted extraction (UAE) without heating. For the reaction conditions, 70 °C for 10 minutes heating is recommended, and UV/Vis reading from 460 to 680 nm. Using the optimized methodology, total saponin contents ranged from 28.43 to 53.09 mg g-1 in the four yerba mate clones. The significant difference in saponin contents between clones indicate great genetic diversity and potential for clones' selection and extraction of these compounds from yerba mate leaves.

Exploration of Raw Pigmented-Fleshed Sweet Potatoes Volatile Organic Compounds and the Precursors.

Sweet potato provides rich nutrients and bioactive substances for the human diet. In this study, the volatile organic compounds of five pigmented-fleshed sweet potato cultivars were determined, the characteristic aroma compounds were screened, and a correlation analysis was carried out with the aroma precursors. In total, 66 volatile organic compounds were identified. Terpenoids and aldehydes were the main volatile compounds, accounting for 59% and 17%, respectively. Fifteen compounds, including seven aldehydes, six terpenes, one furan, and phenol, were identified as key aromatic compounds for sweet potato using relative odor activity values (ROAVs) and contributed to flower, sweet, and fat flavors. The OR sample exhibited a significant presence of trans-ß-Ionone, while the Y sample showed high levels of benzaldehyde. Starch, soluble sugars, 20 amino acids, and 25 fatty acids were detected as volatile compounds precursors. Among them, total starch (57.2%), phenylalanine (126.82 ± 0.02 g/g), and fatty acids (6.45 µg/mg) were all most abundant in Y, and LY contained the most soluble sugar (14.65%). The results of the correlation analysis revealed the significant correlations were identified between seven carotenoids and trans-ß-Ionone, soluble sugar and nerol, two fatty acids and hexanal, phenylalanine and 10 fatty acids with benzaldehyde, respectively. In general, terpenoids and aldehydes were identified as the main key aromatic compounds in sweet potatoes, and carotenoids had more influence on the aroma of OR than other cultivars. Soluble sugars, amino acids, and fatty acids probably serve as important precursors for some key aroma compounds in sweet potatoes. These findings provide valuable insights for the formation of sweet potato aroma.

Ultrasonic-assisted activated carbon separation removing bacterial endotoxin from salvia miltiorrhizae injection.

Ultrasonic-assisted activated carbon separation (UACS) was first employed to improve product quality by regulating adsorption rate and removing bacterial endotoxin from salvia miltiorrhizae injection. The adsorption rate was related to three variables: activated carbon dosage, ultrasonic power, and pH. With the increase of activated carbon dosage from 0.05 % to 1.0 %, the adsorption rates of salvianolic acids and bacterial endotoxin increased simultaneously. The adsorption rates at which bacteria endotoxins increased from 52.52 % to 97.16 % were much higher than salvianolic acids. As the ultrasonic power increased from 0 to 700 W, the adsorption rates of salvianolic acids on activated carbon declined to less than 10 %, but bacterial endotoxin increased to more than 87 %. As the pH increased from 2.00 to 8.00, the adsorption rate of salvianolic acid dropped whereas bacterial endotoxin remained relatively stable. On the basis of response surface methodology (RSM), the optimal separation conditions were established to be activated carbon dose of 0.70 %, ultrasonic power of 600 W, and pH of 7.90. The experimental adsorption rates of bacterial endotoxin were 94.15 %, which satisfied the salvia miltiorrhizae injection quality criterion. Meanwhile, salvianolic acids' adsorption rates were 1.92 % for tanshinol, 4.05 % for protocatechualdehyde, 2.21 % for rosmarinic acid, and 3.77 % for salvianolic acid B, all of which were much lower than conventional activated carbon adsorption (CACA). Salvianolic acids' adsorption mechanism on activated carbon is dependent on the component's molecular state. Under ideal separation conditions, the molecular states of the four salvianolic acids fall between 1.13 % and 6.60 %. The quality of salvia miltiorrhizae injection can be improved while maintaining injection safety by reducing the adsorption rates of salvianolic acids to less than 5 % by the use of ultrasound to accelerate the desorption mass transfer rate on the activated carbon surface. When activated carbon adsorption was used in the process of producing salvia miltiorrhizae injection, the pH of the solution was around 5.00, and the proportion of each component's molecular state was tanshinol 7.05 %, protocatechualdehyde 48.93 %, rosmarinic acid 13.79 %, and salvianolic acid B 10.28 %, respectively. The loss of useful components was evident, and the corresponding activated carbon adsorption rate ranged from 20.74 % to 41.05 %. The average variation rate in plasma His and IgE was significant (P < 0.05) following injection of 0.01 % activated carbon, however the average variation rate of salvia miltiorrhizae injection was dramatically decreased with the use of UACS and CACA (P > 0.05). The ultrasonic at a power intensity of 60 W/L and the power density of 1.20 W/cm2 may resolve the separation contradiction between salvianolic acids and bacterial endotoxin, according to experiments conducted with UACS at different power intensities. According to this study, UACS has a lot of potential applications in the pharmaceutical manufacturing industry and may represent a breakthrough in the field of ultrasonic separation.

Biosynthetic Pathway and Bioactivity of Vanillin, a Highly Abundant Metabolite Distributed in the Root Cortex of Tea Plants (Camellia sinensis).

Volatiles are important for plant root stress resistance. The diseases in tea root are serious, causing major losses. The volatile composition in tea root and whether it can resist diseases remain unclear. In this study, the volatile composition in different tea tissues was revealed. The vanillin content was higher in the root (mainly in root cortex) than in aerial parts. The antifungal effects of vanillin on pathogenic fungi in tea root were equal to or greater than those of other metabolites. O-methyltransferase (CsOMT), a key enzyme in one of two biosynthetic pathways of vanillin, converted protocatechualdehyde to vanillin in vitro. Furthermore, its characteristics and kinetic parameters were studied. In Arabidopsis thaliana protoplasts, the transiently expressed CsOMT was localized in the cytoplasm and nucleus. These findings have clarified the formation and bioactivities of volatiles in tea roots and provided a theoretical basis for understanding how tea plants resist root diseases.

Pharmacological Basis for the Antidiarrheal and Antispasmodic Effects of Cuminaldehyde in Experimental Animals: In Silico, Ex Vivo and In Vivo Studies.

BACKGROUND: Medicinal herbs are frequently used for the management of gastrointestinal disorders because they contain various compounds that can potentially amplify the intended therapeutic effects. Cuminaldehyde is a plant-based constituent found in oils derived from botanicals such as cumin, eucalyptus, myrrh, and cassia and is responsible for its health benefits. Despite the utilization of cuminaldehyde for several medicinal properties, there is currently insufficient scientific evidence to support its effectiveness in treating diarrhea. Hence, the present investigation was carried out to evaluate the antidiarrheal and antispasmodic efficacy of cuminaldehyde, with detailed pharmacodynamics explored. METHODS: An in vivo antidiarrheal test was conducted in mice following the castor oil-induced diarrhea model, while an isolated small intestine obtained from rats was used to evaluate the detailed mechanism(s) of antispasmodic effects. RESULTS: Cuminaldehyde, at 10 and 20 mg/kg, exhibited 60 and 80% protection in mice from episodic diarrhea compared to the saline control group, whereas this inhibitory effect was significantly reversed in the pretreated mice with glibenclamide, similar to cromakalim, an ATP-dependent K+ channel opener. In the ex vivo experiments conducted in isolated rat tissues, cuminaldehyde reversed the glibenclamide-sensitive low K+ (25 mM)-mediated contractions at significantly higher potency compared to its inhibitory effect against high K+ (80 mM), thus showing predominant involvement of ATP-dependent K+ activation followed by Ca++ channel inhibition. Cromakalim, a standard drug, selectively suppressed the glibenclamide-sensitive low K+-induced contractions, whereas no relaxation was observed against high K+, as expected. Verapamil, a Ca++ channel inhibitor, effectively suppressed both low and high K+-induced contractions with similar potency, as anticipated. At higher concentrations, the inhibitory effect of cuminaldehyde against Ca++ channels was further confirmed when the preincubated ileum tissues with cuminaldehyde (3 and 10 mM) in Ca++ free medium shifted CaCl2-mediated concentration-response curves (CRCs) towards the right with suppression of the maximum peaks, similar to verapamil, a standard Ca++ ion inhibitor. CONCLUSIONS: Present findings support the antidiarrheal and antispasmodic potential of cuminaldehyde, possibly by the predominant activation of ATP-dependent K+ channels followed by voltage-gated Ca++ inhibition. However, further in-depth assays are recommended to know the precise mechanism and to elucidate additional unexplored mechanism(s) if involved.

Assessment of antiarthritic potential of Asparagus dumosus using formaldehyde and CFA-induced arthritic models in rats via modulation of oxidative stress biomarkers and mRNA expression of IL-1b, IL-6, RANKL, OPG, TNF-α and COX-2.

Medicinal plants play a pivotal role in the prevention of chronic non-communicable diseases including arthritis. Despite the traditional use of Asparagus dumosus in arthritis, it has not been studied yet for its effectiveness in arthritis. This study was aimed to explore the antiarthritic potential of A. dumosus in formaldehyde and complete Freund's adjuvant (CFA)-induced arthritic rats. Body weight, arthritic index, hepatic oxidative stress, hematological, biochemical and inflammatory markers were assessed using ELISA, whilst qRT-PCR studies were carried out for the mRNA expression of IL-1b, IL-6, RANKL, OPG, TNF-α and COX-2 genes. GCMS and HPLC analysis were performed to identify the secondary metabolites of A. dumosus. From day 8 to 28 post-administration of formaldehyde and CFA, oral administration of A. dumosus (600, 300 and 150 mg/kg) showed a noteworthy improvement (p < 0.001) in the body weights, immune organ weights, serum levels of rheumatoid (RA) factor, C-reactive protein, TNF-α and IL-6 levels in arthritic rats similar to the effect of piroxicam and methotrexate. Subsequently, the administration of A. dumosus to formaldehyde and CFA-challenged rats, caused a marked decrease (p < 0.001) in the mRNA expression of IL-1b, IL-6, OPG, RANKL, TNF-α and COX-2 genes in treated rats. Likewise, when assessed for antioxidant potential, A. dumosus produced a pronounced (p < 0.001) reduction in malondialdehyde (MDA) levels and hydrogen peroxide (H2O2) production, whilst a dose-dependent (p < 0.001) increase in catalase (CAT) and superoxide dismutase (SOD) activities was recorded. GCMS profiling of A. dumosus presented benzaldehyde, 3-hydroxy-4-methoxy-, 1-decanol and undecane as plant compositions, whereas HPLC fingerprinting displayed quercetin, benzaldehyde, 3-hydroxy-4-methoxy-, gallic acid and cinnamic acid as plants constituents. These results depict that A. dumosus possesses anti-arthritic effect mediated possibly through attenuation of arthritic indices, chronic inflammatory and oxidative stress biomarkers along with down-regulation in the mRNA expression of arthritic candid genes.

Nature-inspired synthesis of antibacterial glucovanillin derivatives.

The ongoing threat of Antimicrobial Resistance (AMR) complicated by the rise of Multidrug-Resistant (MDR) pathogens calls for increased efforts in the search for novel treatment options. While deriving inspiration from antibacterial natural compounds, this study aimed at using synthetic approaches to generate a series of glucovanillin derivatives and explore their antibacterial potentials. Among the synthesized derivatives, optimum antibacterial activities were exhibited by those containing 2,4- and 3,5-dichlorophenylamino group coupled to a glucovanillin moiety (compounds 6h and 8d respectively). In those compounds, the Minimum Inhibitory Concentrations (MIC) of 128-256 µg/mL were observed against reference and MDR strains of Klebsiella pneumoniae, Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE). Moreover, these findings emphasize the claims from previous reports on the essence of smaller molecular size, the presence of protonatable amino groups and halogens in potential antibacterial agents. The observed moderate and broad-spectrum activities of the stated derivatives point to their suitability as potential leads towards further efforts to improve their antibacterial activities.

Coffee-waste templated CeOx/TiO2 nanostructured materials for selective photocatalytic oxidations.

An environmentally friendly solvent-free approach was tested using spent coffee as a biomass sacrificial template for the preparation of TiO2 modified with CeOx. The use of coffee as a template pursues the preparation of a nanostructured heterojunction without the need for a solvent. Two variables were optimized in the synthesis process, i.e. calcination temperature and proportion of CeOx. Firstly, bare coffee-template titania was prepared to explore the effect of the calcination temperature, within 500-650 °C. The anatase phase was obtained up to 600 °C. Higher temperatures, i.e. 650 °C, led to the appearance of rutile (10%) and efficient removal of the sacrificial agent (0.6% residue). The maximum photocatalytic activity in terms of conversion, in the oxidation of benzyl alcohol, was achieved employing the bare coffee-template TiO2 at 650 °C, and it was found comparable to the benchmarked P25. The incorporation of ceria in the solvent-free approach considerably improved photocatalytic benzaldehyde production. No changes in the XRD pattern of TiO2 were appreciated in the presence of ceria due to the low amount added, within 1.5-6.0%, confirmed by XPS as superficial Ce3+/Ce4+. The UV-visible absorption spectra were considerably redshifted in the presence of Ce, reducing the bandgap values of bare titania. An optimum amount of ceria in the structure within 3-0% was found. In this case, the selectivity towards benzaldehyde was ca. 75%, 3 times higher than the selectivity value registered for the benchmarked P25 or the bare prepared TiO2.

δ18O compound-specific stable isotope assessment: An advanced analytical strategy for sophisticated adulterations detection in essential oils - Application to spearmint, cinnamon, and bitter almond essential oils authentication.

Natural plant extracts are primarily used as raw materials in the cosmetic and perfumery industry. However, adulterations with petrochemical products are occurring in the market, leading to non-100% natural products. Several analytical techniques such as impurity detection or enantioselective ratio assessments have been previously described as good indicators to detect any addition of synthetic products, but these techniques are ineffective with novel type of synthetic pathways such as semisynthesis. In order to improve authentication, development of advanced analytical strategies such as δ18O stable isotopic ratios assessment was tested on spearmint, cinnamon and bitter almond essential oils major metabolites (carvone, (E)-cinnamaldehyde, and benzaldehyde). Natural δ18O mean values (δ18OCarvone = 18.4‰; δ18OCinnamaldehyde = 13.9‰; δ18OBenzaldehyde = 16.5‰) were found to be higher than semisynthetic origin for the 3 studied molecules (δ18OCarvone = 9.2‰; δ18OCinnamaldehyde = 8.8‰; δ18OBenzaldehyde = 10.9‰). These measurements proved to be efficient to discriminate natural and semisynthetic origins of these components and therefore potentially lead to a novel way to authenticate natural products.

Phenolic Constituents from Wendlandia tinctoria var. grandis (Roxb.) DC. Stem Deciphering Pharmacological Potentials against Oxidation, Hyperglycemia, and Diarrhea: Phyto-Pharmacological and Computational Approaches.

Wendlandia tinctoria var. grandis (Roxb.) DC. (Family: Rubiaceae) is a semi-evergreen shrub distributed over tropical and subtropical Asia. The present research intended to explore the pharmacological potential of the stem extract of W. tinctoria, focusing on the antioxidant, hypoglycemic, and antidiarrheal properties, and to isolate various secondary metabolites as mediators of such activities. A total of eight phenolic compounds were isolated from the dichloromethane soluble fraction of the stem extract of this plant, which were characterized by electrospray ionization (ESI) mass spectrometric and 1H NMR spectroscopic data as liquiritigenin (1), naringenin (2), apigenin (3), kaempferol (4), glabridin (5), ferulic acid (6), 4-hydroxybenzoic acid (7), and 4-hydroxybenzaldehyde (8). The dichloromethane soluble fraction exhibited the highest phenolic content (289.87 ± 0.47 mg of GAE/g of dried extract) and the highest scavenging activity (IC50 = 18.83 ± 0.07 µg/mL) against the DPPH free radical. All of the isolated compounds, except 4-hydroxybenzaldehyde, exerted a higher antioxidant effect (IC50 = 6.20 ± 0.10 to 16.11 ± 0.02 µg/mL) than the standard butylated hydroxytoluene (BHT) (IC50 = 17.09 ± 0.01 µg/mL). Significant hypoglycemic and antidiarrheal activities of the methanolic crude extract at both doses (200 mg/kg bw and 400 mg/kg bw) were observed in a time-dependent manner. Furthermore, the computational modeling study supported the current in vitro and in vivo findings, and the isolated constituents had a higher or comparable binding affinity for glutathione reductase and urase oxidase enzymes, glucose transporter 3 (GLUT 3), and kappa-opioid receptor, inferring potential antioxidant, hypoglycemic, and antidiarrheal properties, respectively. This is the first report of all of these phenolic compounds being isolated from this plant species and even the first demonstration of the plant stem extract's antioxidant, hypoglycemic, and antidiarrheal potentials. According to the current findings, the W. tinctoria stem could be a potential natural remedy for treating oxidative stress, hyperglycemia, and diarrhea. Nevertheless, further extensive investigation is crucial for thorough phytochemical screening and determining the precise mechanisms of action of the plant-derived bioactive metabolites against broad-spectrum molecular targets.

p-hydroxy benzaldehyde revitalizes the microenvironment of peri-infarct cortex in rats after cerebral ischemia-reperfusion.

BACKGROUND: The formation of glial scar around the ischemic core following cerebral blood interruption exerts a protective effect in the subacute phase but impedes neurorepair in the chronic phase. Therefore, the present study aimed to explore whether p-hydroxy benzaldehyde (p-HBA), a phenolic compound isolated from Gastrodia elata Blume, can cut the Gordian knot of glial scar and promote brain repair after cerebral ischemia. METHODS: The effects of p-HBA on neurorepair were evaluated using a rat model of transient middle cerebral artery occlusion (tMCAO). The motor functions were evaluated by neurobehavioral tests, the pathophysiological processes in the peri-infarct cortex (PIC) were detected by viral-based lineage tracking or immunofluorescence staining, and the putative signaling pathway was analyzed by western blot. RESULTS: Administration of p-HBA in the acute stage after stroke onset alleviated the motor impairment in tMCAO rats in a time-dependent manner. The corresponding cellular events were inhibition of astrogliosis, facilitating the conversion of reactive astrocytes (RAs) into neurons, and prompting angiogenesis in PIC, thereby protecting the structure of the neurovascular unit (NVU). One of the underlying molecular mechanisms is the activation of the neurogenic switch of the Wnt/ß-catenin signaling pathway. Notably, p-HBA only promotes astrocyte-to-neuron conversion in the PIC, and only partial RAs were converted to neurons. This pattern of conversion ensures that the brain structure remains unaltered, and the beneficial role of glial scarring is preserved during the subacute phase after ischemia. CONCLUSIONS: These results provided a potential approach to address the dilemma of glial scarring after brain injury, i.e., the pharmacological promotion of astrocyte-to-neuron conversion in the PIC without interfering with normal brain tissue, which mitigates but does not eliminate the glial scar. Subsequently, the neuron rescue-unfriendly environment is switched to a beneficial reconstruction milieu in PIC, which is conducive to neurorepair. Moreover, p-HBA could be a candidate for pharmacological intervention.

Electroreductive CO coupling of benzaldehyde over SACs Au-NiMn2O4 spinel synergetic composites.

Electroreductive CO coupling provides a prospective strategy for biomass derivative upgrading via reducing the number of oxygen-containing functional groups and increasing their molecular weight. However, exploring superior electrocatalysts with effective reactivity and high selectivity for target products are still a challenge. In this work, single atom Au surface derived NiMn2O4 (SACs Au-NiMn2O4) spinel synergetic composites were fabricated by a versatile adsorption-deposition method and applied in electroreductive self-coupling of benzaldehyde to dibenzyl ether. The SACs Au-NiMn2O4 spinel synergetic composites enhanced electroreductive coupling of benzaldehyde, significantly improved the yield and selectivity of dibenzyl ether. Systematic characterizations and density functional theory calculation revealed that atomically dispersed Au occupied surface Ni2+ vacancies, which played a dominated role in CO coupling of benzaldehyde. Detailed calculation results showed that benzaldehyde preferred to adsorb on Ni octa-hedral sites of NiMn2O4 spinel synergetic structure, single atom Au surficial derivation over NiMn2O4 further reduced the adsorption energy (Eads) of benzaldehyde on SACs Au-NiMn2O4, thus the CO coupling of benzaldehyde to dibenzyl ether was promoted. Moreover, single atom Au surficial derivation lowered the energy barrier of rate-determining step, facilitated the formation of dibenzyl ether species. Our work also paves an avenue for rational design single atom materials using spinel as support.

Real-world data on voxelotor to treat patients with sickle cell disease.

OBJECTIVES: The aim of this single-center chart review was to quantify the hematologic response and validated reported outcomes with voxelotor treatment. METHODS: Real-world data were collected retrospectively in patients with sickle cell disease (12-70 years old) who were treated with standard-of-care procedures. Data were collected before and during voxelotor treatment. RESULTS: A total of 77 patients with a mean age of 30.4 years were included in the analysis; 30% of patients were children <21 years old. Most patients were female (62%), had a homozygous hemoglobin S (HbSS) genotype (86%), and were treated with concomitant hydroxyurea (HU; 82%). The mean baseline Hb level was 8.3 g/dl, reticulocyte percentage was 11.5%, and total bilirubin was 3.5 mg/dl. The mean duration of voxelotor treatment was 9.7 months (range: 1.9-17 months). Favorable responses to voxelotor treatment and signs of hematologic response after voxelotor treatment included increased Hb levels, decreased reticulocyte percentage, and decreased total bilirubin. In patients treated with concomitant HU, a more robust improvement was noted versus voxelotor alone, suggesting a complementary effect. Recorded adverse events were rare, mild, and self-limited and resolved with dose modification. CONCLUSIONS: Hematologic improvements were observed after voxelotor treatment, with a potential additive benefit with concomitant HU treatment.

The predominance of endothelium-derived relaxing factors and beta-adrenergic receptor pathways in strong vasorelaxation induced by 4-hydroxybenzaldehyde in the rat aorta.

4-hydroxybenzaldehyde (4HB), known as ρ-hydroxybenzaldehyde, is commonly present in traditional Chinese medicine herb, most frequently used for hypertension treatment. This research aims to determine the potency of 4HB's vasorelaxant action. In the study, the vasodilation effect of 4HB was evaluated using in vitro isolated rat aortic rings assay. The aortic rings were pre-incubated with respective antagonists before being pre-contracted with phenylephrine (PE) and challenged with various concentrations of 4HB for mechanistic action studies. Rmax (maximal vasodilation) and pEC50 (negative logarithm of half-maximal effective concentration) values of each experiment were determined for comparison purposes. 4HB caused vasodilation on endothelium-intact aortic rings which pre-contracted with PE (pEC50 = 3.53 ± 0.05, Rmax = 100.95 ± 4.25%) or potassium chloride (pEC50 = 2.96 ± 0.13, Rmax = 72.13 ± 4.93%). The vasodilation effect of 4HB was significantly decreased in the absence of an endothelium (pEC50 = 2.21 ± 0.25, Rmax = 47.96 ± 4.16%). The atropine, 4-aminopyridine, Nω-nitro-L-arginine methyl ester, glibenclamide, and propranolol significantly reduced the vasorelaxation effect of 4HB. Besides that, 4HB blocked the voltage-operated calcium channel (VOCC) and regulated the intracellular Ca2+ release from the sarcoplasmic reticulum (SR) in the aortic ring. Thus, the results indicated that 4HB exerted its vasodilatory effect via cGMP and ß2 pathways, M3-dependent PLC/IP3 pathways, and potassium and calcium channels.

A chalcone-syringaldehyde hybrid inhibits triple-negative breast cancer cell proliferation and migration by inhibiting CKAP2-mediated FAK and STAT3 phosphorylation.

BACKGROUND: Although triple-negative breast cancer (TNBC) accounts for only 15% of breast cancer cases, it is associated with a high relapse rate and poor outcome after standard treatment. Currently, the effective drugs and treatment strategies for TNBC remain limited, and thus, developing effective treatments for TNBC is pressing. Several studies have demonstrated that both chalcone and syringaldehyde have anticancer effect, but their potential anti-TNBC bioactivity are still unknown. PURPOSE: The present study aimed to synthesize a chalcone-syringaldehyde hybrid (CSH1) and explore its potential anti-TNBC effects and the underlying molecular mechanism. METHODS: Cell cytotoxicity was determined by 3-(4,5-dimethythiazol)-2,5-diphenyltetrazolium bromide (MTT). The activity of cell proliferation was measured by colony formation assay and 5-ethynyl-2'-deoxyuridine (EdU) staining assay. Cell cycle distribution and cell apoptosis were determined by fluorescence-activated cell sorter (FACS). The situation of DNA damage was observed using fluorescence microscopy. The ability of cell-matrix adhesion, migration and invasion was detected using cell adhesion assay and transwell assay. Transcriptome sequencing was performed to find out the changed genes. Levels of various signaling proteins were assessed by western blotting. RESULTS: CSH1 treatment triggered DNA damage and inhibited DNA replication, cell cycle arrest, and cell apoptosis via suppressing signal transducer and activator of transcription 3 (STAT3) phosphorylation. Whole genome RNA-seq analysis suggested that 4% of changed genes were correlated to DNA damage and repair, and nearly 18% of changed genes were functionally related to cell adhesion and migration. Experimental evidence indicated that CSH1 treatment significantly affected the distribution of focal adhesion kinase (FAK) and its phosphorylation, resulting in cell-matrix-adhesion reduction and migration inhibition of TNBC cells. Further mechanistic studies indicated that CSH1 inhibited TNBC cell proliferation, adhesion, and migration by inhibiting cytoskeleton-associated protein 2 (CKAP2)-mediated FAK and STAT3 phosphorylation signaling. CONCLUSION: These results suggest that CKAP2-mediated FAK and STAT3 phosphorylation signaling is a valuable target for TNBC treatment, and these findings also reveal the potential of CSH1 as a prospective TNBC drug.

Degradation of sulfonamides in aquaculture wastewater by laccase-syringaldehyde mediator system: Response surface optimization, degradation kinetics, and degradation pathway.

As a new type of environmental pollutant, environmental antibiotic residues have attracted widespread attention, and the degradation and removal of antibiotics has become an engaging topic for scholars. In this paper, Novozym 51003 industrialized laccase and syringaldehyde were combined to degrade sulfonamides in aquaculture wastewater. Design Expert10 software was used for multiple regression analysis, and a response surface regression model was established to obtain the optimal degradation parameters. In the actual application, the degradation system could maintain a stable performance within 9 h, and timely supplement of the mediator could achieve a better continuous degradation effect. Low concentrations of heavy metals and organic matter would not significantly affect the degradation performance of the laccase-mediator system, making the degradation system suitable for a wide range of water quality. Enzymatic reaction kinetics demonstrated a strong affinity of sulfadiazine to the substrate. Ten degradation products were speculated using high-resolution mass spectrum based on the mass/charge ratios and the publication results. Four types of possible degradation pathways of sulfadiazine were deduced. This work provides a practical method for the degradation and removal of sulfonamide antibiotics in actual sewage.

Chitosan/benzyloxy-benzaldehyde modified ZnO nano template having optimized and distinct antiviral potency to human cytomegalovirus.

Utilization of biomolecules encapsulated nano particles is currently originating ample attention to generate unconventional nanomedicines in antiviral research. Zinc oxide nanoparticle has been extensively studied for antimicrobial, antifungal and antifouling properties due to high surface to volume ratios and distinctive chemical as well as physical properties. Nevertheless, still minute information is available on their response on viruses. Here, in situ nanostructured and polysaccharide encapsulated ZnO NPs are fabricated with having antiviral potency and low cytotoxicity (%viability ~ 90%) by simply controlling the formation within interspatial 3D networks of hydrogels through perfect locking mechanism. The two composites ChH@ZnO and ChB@ZnO shows exceedingly effective antiviral activity toward Human cytomegalovirus (HCMV) having cell viability 93.6% and 92.4% up to 400 µg mL-1 concentration. This study brings significant insights regarding the role of ZnO NPs surface coatings on their nanotoxicity and antiviral action and could potentially guide to the development of better antiviral drug.

Natural products can be used in therapeutic management of COVID-19: Probable mechanistic insights.

The unexpected emergence of the new Coronavirus disease (COVID-19) has affected more than three hundred million individuals and resulted in more than five million deaths worldwide. The ongoing pandemic has underscored the urgent need for effective preventive and therapeutic measures to develop anti-viral therapy. The natural compounds possess various pharmaceutical properties and are reported as effective anti-virals. The interest to develop an anti-viral drug against the novel severe acute respiratory syndrome Coronavirus (SARS-CoV-2) from natural compounds has increased globally. Here, we investigated the anti-viral potential of selected promising natural products. Sources of data for this paper are current literature published in the context of therapeutic uses of phytoconstituents and their mechanism of action published in various reputed peer-reviewed journals. An extensive literature survey was done and data were critically analyzed to get deeper insights into the mechanism of action of a few important phytoconstituents. The consumption of natural products such as thymoquinone, quercetin, caffeic acid, ursolic acid, ellagic acid, vanillin, thymol, and rosmarinic acid could improve our immune response and thus possesses excellent therapeutic potential. This review focuses on the anti-viral functions of various phytoconstituent and alkaloids and their potential therapeutic implications against SARS-CoV-2. Our comprehensive analysis provides mechanistic insights into phytoconstituents to restrain viral infection and provide a better solution through natural, therapeutically active agents.

Fabrication and characterization of magnetic molecularly imprinted polymer based on deep eutectic solvent for specific recognition and quantification of vanillin in infant complementary food.

A magnetic molecularly imprinted polymer based on deep eutectic solvent was synthesized for specific identification and quantification of vanillin. Fe3O4@SiO2-CC and deep eutectic solvent were applied as the carrier of magnetic material and functional monomer, respectively. According to composition and morphology characterizations and adsorption kinetics, the imprinted polymer had excellent advantages on adsorption capacity and identification specificity for vanillin compared with non-imprinted polymer, while its reusability still remained stable. According to the high-performance liquid chromatography, the detection method based on imprinted polymer produced satisfactory analytical results. The limit of quantification was 0.2 µg·mL-1. The mean spiked recoveries for vanillin ranged from 91.2% to 100.2% with intra- and inter-day precision were both less than 7.2%. Compared to traditional extraction methods, this method presented best adsorption and extraction performances. In summary, the method could be further applied to the specific separation and quantification of vanillin in infant complementary food.