Cytotoxic activity of silver nanoparticles prepared from Psidium guajava L. (Myrtaceae) and Lawsonia inermis L. (Lythraceae) extracts

Purpose: To biosynthesize silver nanoparticles (AgNPs) using Psidium guajava L. and Lawsonia inermis L. leaf extracts, and investigate their antioxidant and cytotoxic activities.Methods: The aqueous extracts were prepared by maceration in distilled H2O followed by partitioning with EtOAc. AgNPs were prepared by treating the extracts with 1 mM AgNO3 and then were characterized by UV-vis and FTIR analyses, and transmission electron microscopy (TEM). MTT cytotoxicity and 2,2`-azinobis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) antioxidant assays were used to assess their cytotoxic and antioxidant properties, respectively.Results: AgNPs from P. guajava and L. inermis extracts exhibited good morphological stability and showed moderate antioxidant activity (68.1 and 71.9%, respectively) compared to their extracts. Equipotent cytotoxicity against HCT-116 and MCF-7 cells was observed for AgNPs derived from P.guajava, while AgNPs derived from L. inermis possessed two-fold cytotoxicity compared to their corresponding extracts. Phytochemical analysis of P. guajava afforded pyrogallol, quercetin, quercetin-3-O-β-xylopyranoside, quercetin-3-O-β-arabinopyranoside, and quercetin-3-O-α-rabinofuranoside, while L. inermis afforded lawsone and luteolin.Conclusion: Flavonoids and phenolics play a major role in reducing Ag+ ions, surface coating, antioxidant, and cytotoxic activities of AgNPs. The biocompatible AgNPs produced by L. inermis demonstrate promising cytotoxic activity that could contribute to new cancer treatments

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

New chalcanonol glycoside from the seeds of saw palmetto: antiproliferative and antioxidant effects

<div><p>A new chalcanonol glycoside dimer, <i>bis</i>-<i>O</i>-[(I-4′) → (II-6′)]-α-hydroxyphloretin-2′-<i>O</i>-β-glucoside (<b>1</b>), in addition to six known compounds, namely ( − )-epicatechin (<b>2</b>) and ( − )-epiafzelechin (<b>3</b>), 4-hydroxybenzoic acid (<b>4</b>), protocatechuic acid (<b>5</b>), methylgallate (<b>6</b>), β-sitosterol (<b>7</b>) and β-sitosterol-3-<i>O</i>-glucoside (<b>8</b>), was isolated from the seeds of saw palmetto. The structures of the isolated compounds were established from the analysis of their MS and 1D and 2D NMR spectroscopic data. The antiproliferative activities of the isolated compounds towards PC3, the human prostate cancer cells were investigated. Amongst the isolated compounds, the new compound and the sterolic derivatives showed antiproliferative effects. Screening of the antioxidant effects of the isolated compounds by 2,2′-azino-<i>bis</i>-(3-ethylbenzthiazoline-6-sulfonic acid radical assay revealed that the isolated phenolics were active free radical scavengers.</p></div

Phytochemical Investigation, Antiulcer, Cyclooxygenase-2, and 15-Lipoxygenase Inhibitory Activities of Echinops erinaceus Kit Tan

Plants of the genus Echinop (Asteraceae) are traditional medicinal plants used to treat several GIT ailments, owing to their diverse bioactive secondary metabolites, including sesquiterpenoids, triterpenoids, phytosterols, phenolics, flavonoids, alkaloids, and essential oils. Echinops erinaceus Kit Tan is a wild perennial herb of the genus Echinops which is endemic to Oman, Saudi Arabia, and Yemen. Currently, there are no previous reports exploring its anti-ulcer and anti-inflammatory effects. Additionally, few reports have described the chemical profile of E. erinaceus Kit Tan. In the current study, the CHCl3 fraction of the aerial parts of the plant was subjected to chromatographic isolation and spectroscopic identification via 1D and 2D NMR, and MS. The plant afforded two new compounds, designated erinaceolic acid (E3) and erinaceoside (E5), in addition to five known compounds, namely taraxasterol acetate (E1), taraxasterol (E2), apigenin (E4), stigmasterol-3-O-&beta;-D-glucoside (E6), and speranskoside (E7). The evaluation of the gastric ulcer protective activity of the total extract and successive fractions of E. erinaceus, using the in vivo ethanol-induced ulcer in rats model, revealed the significant effect of the tested extracts and fractions on the percentage of gastric ulcer protection and ulcer index (500 mg/kg) compared to antodine (20 mg/kg). The tested extracts and fractions also reduced the stomach contents of TNF-&alpha; and reduced IL-6 as compared to the untreated group. Histopathological examination of the gastric mucosal tissues of rats supportedprevious results. In addition, the main subfractions and their isolates were assessed for their in vitro anti-inflammatory activity against COX-2 and 15-LOX enzymes. The new compounds erinaceolic acid (E3) and speranskoside (E7) exhibited strong inhibition against COX-2 (3.41 and 2.62 &micro;g/mL) and 15-LOX (10.05 and 5.51 &micro;g/mL), respectively. A molecular docking study was performed to reveal the binding interaction modes of the most active compounds against the binding sites of COX-2 (PDB ID 3LN1) and 15-LOX (PDB ID 1LOX) proteins. Speranskoside (E7) showed a dual binding affinity better than that of the cocrystallized references, celecoxib and (2E)-3-(2-oct-1-yn-1-ylphenyl)acrylic acid (RS7) against both enzymes. This study shed a light on the potential use of E. erinaceus in the protection and treatment of gastric ulcers

Antimicrobial and antiquorum-sensing activity of <i>Ricinus communis</i> extracts and ricinine derivatives

<p>Ricinine (<b>1</b>), a known major alkaloid in <i>Ricinus communis</i> plant, was used as a starting compound for the synthesis of six ricinine derivatives; two new and four known compounds. The new derivatives; 3-amino-5-methyl-1<i>H</i>-pyrazolo[4,3-c]pyridin-4(5<i>H</i>)-one (<b>2</b>), and 3-amino-5-methyl-1-(phenylsulfonyl)-1<i>H</i>-pyrazolo[4,3-c]pyridin-4(5<i>H</i>)-one (<b>3</b>), as well as the previously prepared derivatives (<b>4</b>–<b>7</b>) were subjected for antimicrobial and antiquorum-sensing evaluation in comparison to different <i>R. communis</i> extracts. Acetyl ricininic acid derivative (<b>5)</b> showed the highest antimicrobial activity among all tested derivatives against <i>Staphylococcus aureus</i>, <i>Escherichia coli</i>, <i>Klebsiella pneumoniae</i>, <i>Pseudomonas aeuroginosa</i> and <i>Candida albicans</i>. However, compound <b>7</b> (4-methoxy-1-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide) showed the highest antiquorum-sensing activity among all tested compounds and extracts. These findings proved the usefulness of ricinine as a good scaffold for the synthesis of new antimicrobial and antiquorum-sensing derivatives in spite of its poor contribution to the antimicrobial activity of the plant extracts.</p

In Vitro and In Silico Investigation of Polyacetylenes from <i>Launaea capitata</i> (Spreng.) Dandy as Potential COX-2, 5-LOX, and BchE Inhibitors

Diverse secondary metabolites are biosynthesized by plants via various enzymatic cascades. These have the capacity to interact with various human receptors, particularly enzymes implicated in the etiology of several diseases. The n-hexane fraction of the whole plant extract of the wild edible plant, Launaea capitata (Spreng.) Dandy was purified by column chromatography. Five polyacetylene derivatives were identified, including (3S,8E)-deca-8-en-4,6-diyne-1,3-diol (1A), (3S)-deca-4,6,8-triyne-1,3-diol (1B), (3S)-(6E,12E)-tetradecadiene-8,10-diyne-1,3-diol (2), bidensyneoside (3), and (3S)-(6E,12E)-tetradecadiene-8,10-diyne-1-ol-3-O-β-D-glucopyranoside (4). These compounds were investigated for their in vitro inhibitory activity against enzymes involved in neuroinflammatory disorders, including cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and butyrylcholinesterase (BchE) enzymes. All isolates recorded weak–moderate activities against COX-2. However, the polyacetylene glycoside (4) showed dual inhibition against BchE (IC50 14.77 ± 1.55 μM) and 5-LOX (IC50 34.59 ± 4.26 μM). Molecular docking experiments were conducted to explain these results, which showed that compound 4 exhibited greater binding affinity to 5-LOX (−8.132 kcal/mol) compared to the cocrystallized ligand (−6.218 kcal/mol). Similarly, 4 showed a good binding affinity to BchE (−7.305 kcal/mol), which was comparable to the cocrystallized ligand (−8.049 kcal/mol). Simultaneous docking was used to study the combinatorial affinity of the unresolved mixture 1A/1B to the active sites of the tested enzymes. Generally, the individual molecules showed lower docking scores against all the investigated targets compared to their combination, which was consistent with the in vitro results. This study demonstrated that the presence of a sugar moiety (in 3 and 4) resulted in dual inhibition of 5-LOX and BchE enzymes compared to their free polyacetylenes analogs. Thus, polyacetylene glycosides could be suggested as potential leads for developing new inhibitors against the enzymes involved in neuroinflammation