In-vitro cytotoxic and anti-inflammatory potential of Asparagus densiflorus meyeri and its phytochemical investigation.

Genus Asparagus is well known for its pharmacological activities and ethnopharmacological applications.  In folk medicine, it is used in the management of several diseases such as diabetes, inflammations, and rheumatism. This work aimed to investigate the potential of Asparagus densiflorus meyeri root & aerial parts extracts as cytotoxic and anti-inflammatory and the investigation of their chemical profile. GC analysis & Folin-Ciocalteu and gravimetric methods were used respectively to estimate the lipoidal, phenolic, and saponin contents. MTT assay was conducted using two cell lines (MCF-7 & HepG2) to investigate the cytotoxic and anti-inflammatory activity using TNF-α stimulated MCF-7 cells through monitoring the level of nitric oxide release and NF-κB gene expression. Preliminary phytochemical investigation indicated that both extracted parts are equally rich in saponins, flavonoids, carbohydrates and/or glycosides, and sterols and/or triterpenes. Palmitic acid and ß sitosterol represented the major saturated fatty acids and sterol, respectively. A significant cytotoxic activity against MCF-7 cells was recorded for DCM extract (IC50 26.13 µg/ml). All tested extracts showed a significant decrease in NO release and NF-κB gene expression thus it possesses a potential anti-inflammatory activity. A. densiflorus meyeri is considered a good candidate as a food supplement for protection from malignancy.

Age-related changes in testicular histological structure, testosterone level, libido and semen traits in male Coturnix quail.

To investigate the effect of age in male quail on testicular weight and histology, sexual libido and semen characteristics, a study was performed on 100 quails at 10, 16, 22, 28 and 34 weeks of age. The body and testicular weights were significantly (p < .05) higher at 16 and 22 than at 28 weeks of age. The circumference and diameter of the seminiferous tubules were significantly (p < .05) higher at 28 and 34 than at 10 and 16 weeks of age. Histological evaluation of testicular slices revealed advanced and effective seminiferous tubes as early as 10 weeks, while spermatogenic activity peaked at 16 weeks of age. The highest semen volume, sperm motility and sperm concentration were observed at weeks of age and then decreased gradually with age. At the same time, the testosterone level and libido were significantly (p < .05) higher at 22 than at 10 weeks of age. Furthermore, the age was positive (p < .05), correlated to seminiferous tubule circumference and diameter, and negative (p < .05), correlated to sperm concentration. In conclusion, the age of quail markedly affected the testicular histological structure, libido, testosterone level and semen characteristics.

Preparation and characterization of nano-emulsion formulations of Asparagus densiflorus root and aerial parts extracts: evaluation of in-vitro antibacterial and anticancer activities of nano-emulsion versus pure plant extract.

OBJECTIVE: Preparation and characterization of nano-emulsion formulations for Asparagus densiflorus aerial and root parts extracts. SIGNIFICANCE: Genus Asparagus is known for its antimicrobial and anticancer activities, however, freeze dried powder of aqueous - alcoholic extract prepared in this study, exhibited a limited water solubility, limiting its therapeutic application. Thus, encapsulation of its phytochemicals into nano-emulsion is proposed as a solution to improve water solubility, and facilitate its clinical translation. METHODS: the composition of extracts for both aerial and root parts of Asparagus densiflorus was identified by HPLC and LC-MS analysis. Nano-emulsion was prepared via homogenization where a mixture of Castor oil: phosphate buffered saline (10 mM, pH 7.4): Tween 80: PEG 600 in a ratio of 10: 5: 2.5: 2.5, respectively. Nano-emulsion formulations were characterized for particle size, polydispersity index (PDI), zeta potential, TEM, viscosity and pH. Then, the antibacterial and anticancer activities of nano-emulsion formulations versus their pure plant counterparts was assessed. RESULTS: The analysis of extracts identified several flavonoids, phenolics, and saponins which were reported to have antimicrobial and anticancer activities. Nano-emulsion formulations were monodispersed with droplet sizes ranging from 80.27 ± 2.05 to 111.16 ± 1.97 nm, and polydispersity index ≤0.3. Nano-emulsion formulations enhanced significantly the antibacterial (multidrug resistant bacteria causing skin and dental soft tissues infections) and anticancer (HuH7, HEPG2, H460 and HCT116) activities compared to their pure plant extract counterparts. CONCLUSION: Employing a nano-delivery system as a carrier for phytochemicals might be an effective strategy to enhance their pharmacological activity, overcome their limitations, and ultimately increase their potential for clinical applications.

Regiospecific Photochemical Synthesis of Methylchrysenes.

Methylated polycyclic aromatic hydrocarbons (PAHs) are suspected to be some of the toxic compounds in crude oil towards marine life and are needed as single compounds for environmental studies. 1-, 3- and 6-methylchrysene (3a,b,c) were prepared as single isomers by photochemical cyclization of the corresponding stilbenoids in the Mallory reaction using stoichiometric amounts of iodine in 82-88% yield. 2-methylchrysene (3d) was prepared by photochemical cyclization where the regioselectivity was controlled by elimination of an ortho-methoxy group under acidic oxygen free conditions in 72% yield. These conditions failed to form 4-methylchrysene from the corresponding stilbenoid. All stilbenoids were made from a common naphthyl Wittig salt and suitably substituted benzaldehydes. We have also demonstrated that methylchrysenes can be oxidized to the corresponding chrysenecarboxylic acids by KMnO4 in modest yields.

Reverse Transcription Loop-Mediated Isothermal Amplification Assay for Ultrasensitive Detection of SARS-CoV-2 in Saliva and Viral Transport Medium Clinical Samples.

The COVID-19 pandemic has underscored the shortcomings in the deployment of state-of-the-art diagnostics platforms. Although several polymerase chain reaction (PCR)-based techniques have been rapidly developed to meet the growing testing needs, such techniques often need samples collected through a swab, the use of RNA extraction kits, and expensive thermocyclers in order to successfully perform the test. Isothermal amplification-based approaches have also been recently demonstrated for rapid severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection by minimizing sample preparation while also reducing the instrumentation and reaction complexity. In addition, there are limited reports of saliva as the sample source, and some of these indicate inferior sensitivity when comparing reverse transcription loop-mediated isothermal amplification (RT-LAMP) with PCR-based techniques. In this paper, we demonstrate an improved sensitivity assay from saliva using a two-step RT-LAMP assay, where a short 10 min RT step is performed with only B3 and backward inner primers before the final reaction. We show that while the one-step RT-LAMP demonstrates satisfactory results, the optimized two-step approach allows detection of only few molecules per reaction and performs significantly better than the one-step RT-LAMP and conventional two-step RT-LAMP approaches with all primers included in the RT step. We show control measurements with RT-PCR, and importantly, we demonstrate RNA extraction-free RT-LAMP-based assays for detection of SARS-CoV-2 from viral transport media and saliva clinical samples.

Polyphenolic Profile of Callistemon viminalis Aerial Parts: Antioxidant, Anticancer and In Silico 5-LOX Inhibitory Evaluations.

Five new compounds viz kaempferol 3-O-(4″-galloyl)-ß-d-glucopyranosyl-(1‴→6″)-O-ß-d-glucopyranoside (1), kaempferol 3-O-ß-d-mannuronopyranoside (2), kaempferol 3-O-ß-d-mannopyranoside (3), quercetin 3-O-ß-d-mannuronopyranoside (4), 2, 3 (S)- hexahydroxydiphenoyl]-d-glucose (5) along with fifteen known compounds were isolated from 80% aqueous methanol extract (AME) of C. viminalis. AME and compounds exerted similar or better antioxidant activity to ascorbic acid using DPPH, O2-, and NO inhibition methods. In addition, compounds 16, 4, and 7 showed cytotoxic activity against MCF-7 cell lines while 3, 7 and 16 exhibited strong activity against HepG2. An in silico analysis using molecular docking for polyphenolic compounds 2, 3, 7, 16 and 17 against human stable 5-LOX was performed and compared to that of ascorbic acid and quercetin. The binding mode as well as the enzyme-inhibitor interactions were evaluated. All compounds occupied the 5-LOX active site and showed binding affinity greater than ascorbic acid or quercetin. The data herein suggest that AME, a source of polyphenols, could be used against oxidative-stress-related disorders.

A Novel Clinically Based Staging System for Gallbladder Cancer.

BACKGROUND: Current staging systems for gallbladder cancer (GBC) are primarily based on surgical pathology and therefore are not relevant for unresectable patients and those undergoing neoadjuvant chemotherapy. METHODS: Patients with a confirmed diagnosis of GBC managed at a tertiary referral center (2000-2016) were included. Independent predictors of overall survival (OS) were identified using multivariable analysis (MVA). A combination of these variables was then assessed to identify a set of factors that provided maximal accuracy in predicting OS, and a nomogram and a new staging system were created based on these factors. Harrell's C-statistic was calculated to evaluate the predictive accuracy of the nomogram and staging system. RESULTS: A total of 528 patients were included in the final analysis. On MVA, factors predictive of poor OS were older age, ECOG performance status, hemoglobin level <9 g/dL, presence of metastases, and alkaline phosphatase (ALP) level >200 U/L. A nomogram and a 4-tier staging system predictive of OS were created using age at diagnosis, ECOG status, tumor size, presence or absence of metastasis, and ALP level. The C-statistic for this novel staging system was 0.71 compared with 0.69 for the TNM staging system (P=.08). In patients who did not undergo surgery, the C-statistics of the novel and TNM staging systems were 0.60 and 0.51, respectively (P<.001). CONCLUSIONS: We created a novel, clinically based staging system for GBC based on nonoperative information at the time of diagnosis that was superior to the TNM staging system in predicting OS in patients who did not undergo surgery, and that performed on par with TNM staging in surgical patients.

Neutrophil to lymphocyte ratio as a prognostic marker in metastatic gallbladder cancer.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has been used as an inflammation based prognostic marker for various malignancies. This study evaluated the association between NLR and overall survival (OS) in patients with metastatic gallbladder cancer (GBC) METHODS: An optimal cut off point for NLR was identified by plotting spline-based hazard ratio curves to identify a threshold effect and patients were divided into two groups, ≥5 or <5. Kaplan-Meier curves were plotted for NLR≥5 and NLR<5 and OS between the two groups. RESULTS: Of the 231 patients included, 138 (60%) had NLR <5 and 93 (40%) had NLR ≥5. There were no significant differences noted in gender, race, and administration of chemotherapy between the two groups. On univariable analysis, patients with NLR ≥5 had a significantly poor OS compared to those with NLR <5 (Median OS: 3.6 vs 8.7 months, p < 0.001). On multivariable analysis, adjusting for age, performance status, albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, platelet count and no administration of chemotherapy, NLR of ≥5 was associated with a worse OS compared to NLR <5 (HR: 1.70, 95%CI:1.20-2.39, p < 0.05). CONCLUSION: The current study demonstrates that NLR ≥5 is an independent predictor of poor prognosis in patients with metastatic GBC.

Design, Synthesis and Antitumor Evaluation of Novel Pyrazolopyrimidines and Pyrazoloquinazolines.

A series of N-aryl-7-aryl-pyrazolo[1,5-a]pyrimidines 18a⁻u and N-aryl-pyrazolo[1,5-a]quinazolines 25a⁻c were designed and synthesized via the reaction of 5-aminopyrazoles 11a⁻c with enaminones 12a⁻g or 19, respectively. The new compounds were screened for their in vitro antitumor activity toward liver (HepG-2) and breast (MCF-7) human cancer cells using 3-[4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide MTT assay. From the results, it was found that all compounds showed dose-dependent cytotoxic activities against both HepG-2 and MCF-7 cells. Two compounds 18o and 18a were selected for further investigations. Cell cycle analysis of liver (HepG-2) cells treated with 18o and breast (MCF-7) cells treated with 18a showed cell cycle arrest at G2/M phase and pro-apoptotic activity as indicated by annexin V-FITC staining.

The indole alkaloid meleagrin, from the olive tree endophytic fungus Penicillium chrysogenum, as a novel lead for the control of c-Met-dependent breast cancer proliferation, migration and invasion.

Fungi of the genus Penicillium produce unique and chemically diverse biologically active secondary metabolites, including indole alkaloids. The role of dysregulated hepatocyte growth factor (HGF) and its receptor, c-Met, in the development and progression of breast carcinoma is documented. The goal of this work is to explore the chemistry and bioactivity of the secondary metabolites of the endophytic Penicillium chrysogenum cultured from the leaf of the olive tree Olea europea, collected in its natural habitat in Egypt. This fungal extract showed good inhibitory activities against the proliferation and migration of several human breast cancer lines. The CH2Cl2 extract of P. chrysogenum mycelia was subjected to bioguided chromatographic separation to afford three known indole alkaloids; meleagrin (1), roquefortine C (2) and DHTD (3). Meleagrin inhibited the growth of the human breast cancer cell lines MDA-MB-231, MDA-468, BT-474, SK BR-3, MCF7 and MCF7-dox, while similar treatment doses were found to have no effect on the growth and viability of the non-tumorigenic human mammary epithelial cells MCF10A. Meleagrin also showed excellent ATP competitive c-Met inhibitory activity in Z-Lyte assay, which was further confirmed via molecular docking studies and Western blot analysis. In addition, meleagrin treatment caused a dose-dependent inhibition of HGF-induced cell migration, and invasion of breast cancer cell lines. Meleagrin treatment potently suppressed the invasive triple negative breast tumor cell growth in an orthotopic athymic nude mice model, promoting this unique natural product from hit to a lead rank. The indole alkaloid meleagrin is a novel lead c-Met inhibitory entity useful for the control of c-Met-dependent metastatic and invasive breast malignancies.

Chemical and biological characterization of Melaleuca subulata (Cheel) Craven leaves' volatile constituents supported by chemometric analysis and molecular docking.

BACKGROUND: The genus Melaleuca (Myrtaceae) comprises dozens of essential oil (EO)-rich species that are appreciated worldwide for their various medicinal values. Additionally, they are renowned in traditional medicine for their antimicrobial, antifungal, and other skin-related activities. The current study investigated the chemical profile and skin-related activities of volatile constituents derived from M. subulata (Cheel) Craven (Synonym Callistemon subulatus) leaves cultivated in Egypt for the first time. METHODS: The volatile components were extracted using hydrodistillation (HD), headspace (HS), and supercritical fluid (SF). GC/MS and Kovat's retention indices were implemented to identify the volatile compounds, while the variations among the components were assessed using Principal Component Analysis and Hierarchical Cluster Analysis. The radical scavenging activity was assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH), oxygen radical absorbance capacity (ORAC) and ß-carotene assays. Moreover, the anti-aging effect was evaluated using anti-elastase, and anti-collagenase, while the antimicrobial potential was deduced from the agar diffusion and broth microdilution assays. Lastly, the molecular docking study was executed using C-docker protocol in Discovery Studio 4.5 to rationalize the binding affinity with targeted enzymes. RESULTS: The SF extraction approach offered the highest EO yield, being 0.75%. According to the GC/MS analysis, monoterpene hydrocarbons were the most abundant volatile class in the HD oil sample (54.95%), with α-pinene being the most copious component (35.17%). On the contrary, the HS and SF volatile constituents were pioneered with oxygenated monoterpenes (72.01 and 36.41%) with eucalyptol and isopulegone being the most recognized components, representing 67.75 and 23.46%, respectively. The chemometric analysis showed segregate clustering of the three extraction methods with α-pinene, eucalyptol, and isopulegone serving as the main discriminating phytomarkers. Concerning the bioactivity context, both SF and HD-EOs exhibited antioxidant effects in terms of ORAC and ß-carotene bleaching. The HD-EO displayed potent anti-tyrosinase activity, whereas the SF-EO exhibited significant anti-elastase properties. Moreover, SF-EO shows selective activity against gram-positive skin pathogens, especially S. aureus. Ultimately, molecular docking revealed binding scores for the volatile constituents; analogous to those of the docked reference drugs. CONCLUSIONS: M. subulata leaves constitute bioactive volatile components that may be indorsed as bioactive hits for managing skin aging and infection, though further in vivo studies are recommended.

Black Titania Janus Mesoporous Nanomotor for Enhanced Tumor Penetration and Near-Infrared Light-Triggered Photodynamic Therapy.

Thanks to their excellent photoelectric characteristics to generate cytotoxic reactive oxygen species (ROS) under the light-activation process, TiO2 nanomaterials have shown significant potential in photodynamic therapy (PDT) for solid tumors. Nevertheless, the limited penetration depth of TiO2-based photosensitizers and excitation sources (UV/visible light) for PDT remains a formidable challenge when confronted with complex tumor microenvironments (TMEs). Here, we present a H2O2-driven black TiO2 mesoporous nanomotor with near-infrared (NIR) light absorption capability and autonomous navigation ability, which effectively enhances solid tumor penetration in NIR light-triggered PDT. The nanomotor was rationally designed and fabricated based on the Janus mesoporous nanostructure, which consists of a NIR light-responsive black TiO2 nanosphere and an enzyme-modified periodic mesoporous organosilica (PMO) nanorod that wraps around the TiO2 nanosphere. The overexpressed H2O2 can drive the nanomotor in the TME under catalysis of catalase in the PMO domain. By precisely controlling the ratio of TiO2 and PMO compartments in the Janus nanostructure, TiO2&PMO nanomotors can achieve optimal self-propulsive directionality and velocity, enhancing cellular uptake and facilitating deep tumor penetration. Additionally, by the decomposition of endogenous H2O2 within solid tumors, these nanomotors can continuously supply oxygen to enable highly efficient ROS production under the NIR photocatalysis of black TiO2, leading to intensified PDT effects and effective tumor inhibition.

UHPLC-MS profiles and antidiarrheal activity of Quercus coccinea münchh. and Quercus robur L. employing in vivo technique.

Introduction: Quercus L. genus (Oak) belongs to the family Fagaceae and their galls are used commercially in leather tanning, dyeing, and ink preparation. Several Quercus species were traditionally used to manage wound healing, acute diarrhea, hemorrhoid, and inflammatory diseases. The present study aims to investigate the phenolic content of the 80% aqueous methanol extract (AME) of Q. coccinea and Q. robur leaves as well as to assess their anti-diarrheal activity. Methods: Polyphenolic content of Q. coccinea and Q. robur AME were investigated using UHPLC/MS. The antidiarrheal potential of the obtained extracts was evaluated by conducting a castor oil-induced diarrhea in-vivo model. Result and Discussion: Twenty-five and twenty-six polyphenolic compounds were tentatively identified in Q. coccinea and Q. robur AME, respectively. The identified compounds are related to quercetin, kaempferol, isorhamnetin, and apigenin glycosides and their aglycones. In addition, hydrolyzable tannins, phenolic acid, phenyl propanoides derivatives, and cucurbitacin F were also identified in both species AME of Q. coccinea (250, 500, and 1000 mg/kg) exhibited a significant prolongation in the onset of diarrhea by 17.7 %, 42.6%, and 79.7% respectively while AME of Q. robur at the same doses significantly prolonged the onset of diarrhea by 38.6%, 77.3%, and 2.4 folds respectively as compared to the control. Moreover, the percentage of diarrheal inhibition of Q. coccinea was 23.8%, 28.57%, and 42,86% respectively, and for Q. robur 33.34%, 47.3%, and 57.14% respectively as compared to the control group. Both extracts significantly decreased the volume of intestinal fluid by 27%, 39.78%, and 50.1% for Q. coccinea respectively; and by 38.71%, 51.19%, and 60% for Q. robur respectively as compared to the control group. In addition, AME of Q. coccinea exhibited a peristaltic index of 53.48, 47.18, and 42.28 with significant inhibition of gastrointestinal transit by 18.98%, 28.53%, and 35.95 % respectively; while AME of Q. robur exhibited a peristaltic index of 47.71, 37, and 26.41 with significant inhibition of gastrointestinal transit by 27.72%, 43.89%, and 59.99% respectively as compared with the control group. Notably, Q. robur showed a better antidiarrheal effect in comparison with Q. coccinea and, the highest effect was observed for Q. robur at 1000 mg/kg as it was nonsignificant from the loperamide standard group in all measured parameters.

Fosfomycin and Its Derivatives: New Scale Inhibitors for Oilfield Applications.

Aminomethylenephosphonate-based scale inhibitors (SIs) have been widely studied and recognized for several decades to mitigate various oilfield scales. However, most of these compounds afforded several drawbacks, such as poor biodegradability and intolerance with the production system. As environmental regulations become more rigid, new production chemicals must adhere to certain criteria to qualify for use in the oil and gas industry, particularly in areas with strict regulations, such as the Norwegian Sea. The low toxicity of fosfomycin encouraged us to test fosfomycin and related molecules as new aminomethylene-free phosphonate SIs for calcite and gypsum scales. The tested chemicals are fosfomycin disodium salt (SI-1), fosfomycin trometamol (SI-2), and hydrolysis of fosfomycin called 1,2-dihydroxypropyl phosphonic acid (SI-3). The inhibition efficiency of all these chemicals was evaluated against calcite and gypsum scales compared to commercial oilfield scale inhibitor hydroxyphosphonoacetic acid (HPAA) according to the NACE Standard TM0374-2007. In addition, the calcite scale inhibition efficiency of all aminomethylene-free phosphonate SIs (SI-1 to SI-3 and HPAA) was investigated based on the Heidrun oilfield, Norway. Moreover, we have reported the calcium compatibility of these chemicals at various concentrations of SIs and calcium ions at 80 °C over 24 h. All new aminomethylene-free phosphonate SIs showed good gypsum and calcite inhibition performance. It was also found that all tested chemicals derived from fosfomycin demonstrated excellent compatibility with calcium ions of up to 1000 ppm throughout the 24 h experiment period compared to HPAA.

Can Micro RNA-24 Affect the Cardiovascular Morbidity in Systemic Lupus Erythematosus by Targeting YKL-40?

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease with inflammatory nature. One of the leading causes of death in SLE patients is cardiovascular (CVS) morbidity. MiRNA-24 is highly expressed in vascular endothelial cells (VECs). This dysregulated expression pattern is associated with dysfunction or even damage of VECs and leads to the occurrence of cardiovascular diseases. YKL- 40 is an inflammatory glycoprotein involved in the pathogenesis of endothelial dysfunction and thereby atherosclerosis. In this work, we aimed at illustrating the possible role of miR-24 and its target YKL-40 in the pathogenesis of the CVS morbidity associated with SLE. Methods: This work was conducted on 40 SLE patients and 40 healthy controls. Quantitative real-time PCR (qPCR) was done to estimate the expression level of miRNA-24 in serum. In addition, we measured the serum level of YKL-40 using ELISA. Results: miR-24-fold change was found to be down-regulated, whereas serum YKL- 40 was up-regulated among SLE patients with observed significant and negative correlation between the two parameters. Conclusion: Our study provided an insight about the role of miR-24 and its target serum YKL-40 protein in the development of SLE-related inflammation and atherosclerosis.

Melaleuca rugulosa (Link) Craven Tannins: Appraisal of anti-inflammatory, radical scavenging activities, and molecular modeling studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Genus Melaleuca or tea tree species are well known to be an important source of biological active oils and extracts. The biological significance appears in their usage for treatment of several clinical disorder owing to their traditional uses as anti-inflammatory, antibacterial, antifungal, and cytotoxic activities. AIM OF THE STUDY: Our study aimed to investigate the metabolic profile of the M. rugulosa polyphenol-rich fraction along with determination of its anti-inflammatory potential, free radical scavenging and antiaging activities supported with virtual understanding of the mode of action using molecular modeling strategy. MATERIALS AND METHODS: The anti-inflammatory activity of the phenolic rich fraction was investigated through measuring its inhibitory activity against inflammatory mediators viz tumor necrosing factor receptor-2 (TNF-α) and cyclooxygenases 1/2 (COX-1/2) in a cell free and cell-based assays. Moreover, the radical scavenging activity was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH), oxygen radical absorbance capacity (ORAC) and ß-carotene assays, while the antiaging activity in anti-elastase, anti-collagenase, and anti-tyrosinase inhibitory assays. Finally, the biological findings were supported with molecular docking study using MOE software. RESULTS: The chromatographic purification of the polyphenol-rich fraction of Melaleuca rugulosa (Link) Craven afforded fourteen phytoconstituents (1-14). The anti-inflammatory gauging experiments demonstrated inhibition of inflammatory-linked enzymes COX-1/2 and the TNF-α at low µg/mL levels in the enzyme-based assays. Further investigation of the underlying mechanism was inferred from the quantification of protein levels and gene expression in the lipopolysaccharide (LPS)-activated murine macrophages (RAW264.7) in vitro model. The results revealed the reduction of protein synthesis of COX-1/2 and TNF-α with the down regulation of gene expression. The cell free in vitro radical scavenging assessment of the polyphenol-rich fraction revealed a significant DPPH reduction, peroxyl radicals scavenging, and ß-carotene peroxidation inhibition. Besides, the polyphenol-rich fraction showed a considerable inhibition of the skin aging-related enzymes as elastase, collagenase, and tyrosinase. Ultimately, the computational molecular modelling studies uncovered the potential binding poses and relevant molecular interactions of the identified polyphenols with their targeted enzymes. Particularly, terflavin C (8) which showed a favorable binding pose at the elastase binding pocket, while rosmarinic acid (14) demonstrated the best binding pose at the COX-2 catalytic domain. In short, natural polyphenols are potential candidates for the management of free radicals, inflammation, and skin aging related conditions. CONCLUSION: Natural polyphenols are potential candidates for the management of free radicals, inflammation, and skin aging related conditions.

Green Synthesis, Characterization, Antimicrobial and Anticancer Screening of New Metal Complexes Incorporating Schiff Base.

A Schiff base ligand of o-vanillin and 4-aminoazobenzene and its transition metal complexes of Ni(II), Co(II), Zn(II), Cu(II), Mn(II), and Zr(IV) were prepared under microwave irradiation as a green approach compared to the conventional method. The structures of new compounds have been characterized and elucidated via elemental and spectroscopic analyses. In addition, magnetic susceptibility, electron spin resonance, and electronic spectra of the synthesized complexes explained their geometrical structures. The thermal stability of Cu(II), Zn(II), and Zr(IV) complexes was studied by thermo-gravimetric analyses (TGA). Coats-Redfern and Horowitz-Metzger equations were used to calculate the thermal and dehydration decomposition activities of proposed structures kinetically. Surface morphologies of the solid compounds were imaged by scanning electron microscopy (SEM). The particle size of prepared complexes was measured by using a particle size analyzer at a diffraction angle of 10.9°. The geometry structures of the synthesized compounds were verified utilizing electronic spectra, ESR spectrum, and magnetic moment value. The newly synthesized compounds were screened for antimicrobial activity. Also, the anticancer activity of the free Schiff base ligand and its metal complexes were studied against two cell lines: human colon (HCT-116) and human liver cancer cells (HepG-2). The obtained results showed that the Cu(II) complex displayed the highest cytotoxic activity (IC50 = 18 and 22 µg/mL for HepG-2 and HCT, respectively) compared to the free Schiff base ligand.

Sulfur-Decorated Ni-N-C Catalyst for Electrocatalytic CO2 Reduction with Near 100 % CO Selectivity.

Developing highly efficient electrocatalysts for electrochemical CO2 reduction (ECR) to value-added products is important for CO2 conversion and utilization technologies. In this work, a sulfur-doped Ni-N-C catalyst is fabricated through a facile ion-adsorption and pyrolysis treatment. The resulting Ni-NS-C catalyst exhibits higher activity in ECR to CO than S-free Ni-N-C, yielding a current density of 20.5 mA cm-2 under -0.80 V versus a reversible hydrogen electrode (vs. RHE) and a maximum CO faradaic efficiency of nearly 100 %. It also displays excellent stability with negligible activity decay after electrocatalysis for 19 h. A combination of experimental investigations and DFT calculations demonstrates that the high activity and selectivity of ECR to CO is due to a synergistic effect of the S and Ni-NX moieties. This work provides insights for the design and synthesis of nonmetal atom-decorated M-N-C-based ECR electrocatalysts.

Ethnopharmacological impact of Melaleuca rugulosa (Link) Craven leaves extract on liver inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Melaleuca species have been used by many ethnic communities for the management and treatment of several ailments as hemorrhoids, cough, skin infections, rheumatism, sore throat, pain, inflammation, and digestive system malfunctions. However, the detailed mechanistic pharmacological effect of Melaleuca rugulosa (Link) Craven leaves in the management of liver inflammation has not been yet addressed. AIM OF THE STUDY: The present study aimed to evaluate the anti-inflammatory, antioxidant, and antiapoptotic capacities of the aqueous methanol extract of M. rugulosa leaves in relevance to their flavonoid content using an appropriate in vivo model. MATERIALS AND METHODS: The aqueous methanol extract of M. rugulosa leaves was administered to the rats at three non-toxic doses (250, 500, and 1000 mg/kg) for seven days prior to the initiation of liver-injury induced by paracetamol (3 g/kg). Liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were evaluated in serum samples. The oxidative stress markers including reduced glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) levels as well as the inflammatory markers such as tumour necrosis factor-alpha (TNF-α) and nuclear factor-kappa B (NF-κB), were assessed in liver homogenate. The results were supported by histopathological and immuno-histochemical studies. The phytochemical investigation of the flavonoid-rich fraction of the aqueous methanol extract was accomplished using different chromatographic and spectroscopic techniques. RESULTS: The aqueous methanol extract of M. rugulosa leaves showed a powerful hepatoprotective activity evidenced by the significant reduction of MDA and NO levels, as well as increasing GSH and catalase activity. Moreover, the extract exhibited anti-inflammatory and antiapoptotic activities witnessed by decreasing TNF-α, NF-κB, iNOS, p-JNK, caspase-3, BAX, and increasing Bcl-2 levels. Moreover, the pretreatment of rats with all doses of M. rugulosa leaves extract showed a significant decrease in liver weight/body weight (LW/BW) ratio, and total bilirubin induced by paracetamol. On the other hand, the chromatographic separation of the flavonoid-rich fraction afforded twenty known flavonoids namely; iso-orientin (1), orientin (2), isovitexin (3), vitexin (4), quercetin-3-O-ß-D-glucuronid methyl ether (5), quercetin-3-O-ß-D-mannuronpyranoside (6), isoquercetin (7), quercitrin (8), kaempferol-3-O-ß-D-mannuronopyranoside (9), kaempferol-7-O-methyl ether-3-O-ß-D-glucopyranoside (10), guaijaverin (11), avicularin (12), kaempferide-3-O-ß-D-glucopyranoside (13), astragalin (14), afzelin (15), luteolin (16), apigenin (17), quercetin (18), kaempferol (19), and catechin (20). CONCLUSION: The aqueous methanol extract of M. rugulosa leaves showed potential hepatoprotective, antioxidant, and anti-inflammatory activities against paracetamol-induced liver inflammation which is correlated at least in part to its considerable phenolic content.

Polyphenolic profile and ethno pharmacological activities of Callistemonsubulatus (Cheel) Craven leaves cultivated in Egypt.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Callistemon (syn. Melaleuca) of the myrtle family (Myrtaceae) has been documented as an integral part in the ethnobotanical system of the indigenous people of Australian mainland and many of its islands. Several Callistemons including the species subulatus were used by aboriginal Australians for making rafts, roofs for shelters, bandages, and food recipes, in addition to the management of wounds, infections, pain, cough, bronchitis, and gastrointestinal tract (GIT) disorders. AIM OF THE STUDY: The current study is designed to document the therapeutic effect of the aqueous methanolic extract (AME) of C. sabulatus Chell (syn. M. sabulata) leaves in the management of diarrhea and pain. Also, its influence on additional pharmacological modalities that are related to oxidative stress just as skin aging. Ultimately, the polyphenolic profile of the extract is disclosed and correlated to the aforementioned bioactivities. MATERIALS AND METHODS: The extract was fractionated using various chromatography techniques and the structures of the isolated compounds were determined based on their chemical and spectral data. The antioxidant activity was assessed using multiple models, including 2,2-diphenyl-picrylhydrazyl (DPPH), oxygen radical absorbance capacity (ORAC) and ß-carotene bleaching assays. The anti-skin aging effect was evaluated using different relevant enzymatic assays. The antinociceptive activity was investigated using acetic acid-induced writhing, hot plate test, and formalin-induced paw licking in mice models. The antidiarrheal activity was gauge using the castor oil induced diarrhea, enter pooling and gastrointestinal motility in vivo models. RESULTS: Diverse polyphenols, including quercetin-3-O-ß-D-glucuronopyranoside (1), kaempferol-3-O-ß-D-glucuronopyranoside (2), strictinin (3), quercetin-3-O-(2``-O-galloyl)-ß-D-glucuronopyranoside (4), afzelin (5), di-galloyl glucose (6), mono-galloyl glucose (7), acacetin (8), apigenin-6,7-dimethyl ether (9), kaempferol trimethyl ether (10), dimethoxy chrysin (11), quercetin (12), kaempferol (13), methyl gallate (14), and gallic acid (15) were identified. The extract exhibited as significant antioxidant activity even better than that of Trolox or BHT. Moreover, it exerts elastase, tyrosinase, and collagenase inhibition activities, in addition to the significant peripheral and central analgesic activity in a dose-dependent manner (P < 0.0001). In castor oil induced diarrhea model, AME significantly prolonged the diarrhea onset, decreased the frequency of defecation, and weight of feces. Likewise, it exhibited a significant reduction in the gastrointestinal motility in charcoal meal model (P < 0.0001) and a considerable inhibitory effect on gastrointestinal transit and peristaltic index with all investigated doses (P < 0.0001). CONCLUSION: Ethnobotanicals are versatile resources for the management of various ailments by indigenous people and the experimental research is utmost to validate and uncover their pharmacological relevance. C. sabulatus leaves have strong antioxidant, analgesic, anti-skin aging, and antidiarrheal activities which are validated for the first time by various in vitro and in vivo models. The metabolic profile of the unprecedented AME of C. sabulatus leaves compromises a wide array of bioactive polyphenolic metabolites including, flavonoids, tannins, and phenolic acids that are correlated to the observed bioactivities. Altogether, ethnobotanicals with high and diverse contents of polyphenols are potential candidates for the management of various human aliments including neuropathies, GIT disorders, and skin aging conditions.