Identification of a Prenyl Chalcone as a Competitive Lipoxygenase Inhibitor: Screening,Biochemical Evaluation and Molecular Modeling Studies

Cyclooxygenase (COX) and lipoxygenase (LOX) are key targets for the development of new anti-inflammatory agents. LOX, which is involved in the biosynthesis of mediators in inflammation and allergic reactions, was selected for a biochemical screening campaign to identify LOX inhibitors by employing the main natural product library of Brazilian biodiversity. Two prenyl chalcones were identified as potent inhibitors of LOX-1 in the screening. The most active compound, (E)-2-O-farnesyl chalcone, decreased the rate of oxygen consumption to an extent similar to that of the positive control, nordihydroguaiaretic acid. Additionally, studies on the mechanism of the action indicated that (E)-2-O-farnesyl chalcone is a competitive LOX-1 inhibitor. Molecular modeling studies indicated the importance of the prenyl moieties for the binding of the inhibitors to the LOX binding site, which is related to their pharmacological properties.     

Characterization of a Robust CoII Fluorescent Complex Deposited Intact On HOPG

The new diimine fluorescent ligand ACRI‐1 based on a central acridine yellow core is reported along with its coordination complex [Co₂( ACRI‐1 )₂] ( 1 ), a fluorescent weak ferromagnet. Due to the strong fluorescence of the acridine yellow fluorophore, it is not completely quenched when the ligand is coordinated to Co^II. The magnetic properties of bulk complex 1 and its stability in solution have been studied. Complex 1 has been deposited on highly ordered pyrolitic graphite (HOGP) from solution. The thin films prepared have been characterized by AFM, time‐of‐flight secondary ion mass spectrometry (TOF‐SIMS), grazing incidence X‐ray diffraction (GIXRD), X‐ray absorption spectroscopy (XAS), X‐ray magnetic circular dichroism (XMCD) and theoretical calculations. The data show that the complex is robust and remains intact on the surface of graphite.     

Chondroitin Sulfate Protects the Liver in an Experimental Model of Extra-Hepatic Cholestasis Induced by Common Bile Duct Ligation

During liver fibrogenesis, there is an imbalance between regeneration and wound healing. The current treatment is the withdrawal of the causing agent; thus, investigation of new and effective treatments is important. Studies have highlighted the action of chondroitin sulfate (CS) in different cells; thus, our aim was to analyze its effect on an experimental model of bile duct ligation (BDL). Adult Wistar rats were subjected to BDL and treated with CS for 7, 14, 21, or 28 days intraperitoneally. We performed histomorphometric analyses on Picrosirius-stained liver sections. Cell death was analyzed according to caspase-3 and cathepsin B activity and using a TUNEL assay. Regeneration was evaluated using PCNA immunohistochemistry. BDL led to increased collagen content with corresponding decreased liver parenchyma. CS treatment reduced total collagen and increased parenchyma content after 21 and 28 days. The treatment also promoted changes in the hepatic collagen type III/I ratio. Furthermore, it was observed that CS treatment reduced caspase-3 activity and the percentage of TUNEL-positive cells after 14 days and cathepsin B activity only after 28 days. The regeneration increased after 14, 21, and 28 days of CS treatment. In conclusion, our study showed a promising hepatoprotective action of CS in fibrogenesis induced by BDL.     

Structure Elucidation of Triterpenoid Saponins Found in an Immunoadjuvant Preparation of Quillaja brasiliensis Using Mass Spectrometry and 1H and 13C NMR Spectroscopy

An immunoadjuvant preparation (named Fraction B) was obtained from the aqueous extract of Quillaja brasiliensis leaves, and further fractionated by consecutive separations with silica flash MPLC and reverse phase HPLC. Two compounds were isolated, and their structures elucidated using a combination of NMR spectroscopy and mass spectrometry. One of these compounds is a previously undescribed triterpene saponin (Qb1), which is an isomer of QS-21, the unique adjuvant saponin employed in human vaccines. The other compound is a triterpene saponin previously isolated from Quillaja saponaria bark, known as S13. The structure of Qb1 consists of a quillaic acid residue substituted with a β-d-Galp-(1→2)-[β-d-Xylp-(1→3)]-β-d-GlcpA trisaccharide at C3, and a β-d-Xylp-(1→4)-α-l-Rhap-(1→2)-[α-l-Arap-(1→3)]-β-d-Fucp moiety at C28. The oligosaccharide at C28 was further substituted at O4 of the fucosyl residue with an acyl group capped with a β-d-Xylp residue.     

Development and Validation of Multi-Residue Method for Drugs Analysis in Human Feces by Liquid Chromatography–Tandem Mass Spectrometry

The use of veterinary drugs in animal production is a common practice to secure animal and human health. However, residues of administrated drugs could be present in animal food products. Levels of drugs in food of animal origin are regulated within the European Union. In recent years, residues have been detected not only in food, but also in the environmental elements such as water or soil, meaning that humans are involuntarily exposed to these substances. This article presents a multiclass method for the analysis of various therapeutic groups of pharmaceuticals in human feces. Pharmaceuticals are extracted from feces with an acid extraction solvent, and after filtration the extract was analyzed by HPLC–MS/MS. A limit of detection of 10 ng/g was achieved for 9 pharmaceuticals, with linearity over 0.99 and repeatability and reproducibility lower than 20%. The method was satisfactorily applied in 25 feces samples of individuals that had declared not to be under medical treatment for the last two months. Results indicate the presence of six different compounds at concentration between 10 and 456 ng/g. This preliminary study showed the involuntary exposure of human gut microbiota to active substances such as pharmaceuticals     

Recovery of Bioactive Ellagitannins by Ultrasound/Microwave-Assisted Extraction from Mexican Rambutan Peel (Nephelium lappaceum L.)

Rambutan (Nephelium lappaceum L.) is a tropical fruit from Asia which has become the main target of many studies involving polyphenolic analysis. Mexico produces over 8 million tons per year of rambutan, generating a huge amount of agro-industrial waste since only the pulp is used and the peel, which comprises around 45% of the fruit’s weight, is left behind. This waste can later be used in the recovery of polyphenolic fractions. In this work, emerging technologies such as microwave, ultrasound, and the hybridization of both were tested in the extraction of phenolic compounds from Mexican rambutan peel. The results show that the hybrid technology extraction yielded the highest polyphenolic content (176.38 mg GAE/g of dry rambutan peel). The HPLC/MS/ESI analysis revealed three majoritarian compounds: geraniin, corilagin, and ellagic acid. These compounds explain the excellent results for the biological assays, namely antioxidant activity evaluated by the DPPH, ABTS, and LOI (Lipid oxidation inhibition) assays that exhibited great antioxidant capacity with IC₅₀ values of 0.098, 0.335, and 0.034 mg/mL respectively, as well as prebiotic activity demonstrated by a µMax (maximum growth) of 0.203 for Lactobacillus paracasei. Lastly, these compounds have shown no hemolytic activity, opening the door for the elaboration of different products in the food, cosmetic, and pharmaceutical industries.     

Test of a rich-prototype detector with solid photocathode for hades

The development of a Ring Imaging CHerenkov (RICH) detector working in an environment of strong hadronic background is needed for the High Acceptance Di-Electron Spectrometer (HADES). To get information about the charged particle background situation, a CERN RICH prototype with solid (CsI) photocathode was tested in a 1×A GeV U+Pb reaction at GSI. Also the quantum efficiency of the CsI photocathode was determined to be 10% at 175 nm.Presented at the International School-Workshop Relativistic Heavy-Ion Physics, Prague (Czech Republic), 19–23 September 1994.For the HADES Collaboration (IOP Bratislava, Univ. Clermont-Ferrand, GSI Darmstadt, Univ. Frankfurt, Univ. Gießen, Univ. Kraków, Univ. Milano, ITEP Moscow, LPI Moscow, MEPI Moscow, TU München, Univ. Nikosia, NPI e, Univ. Valencia).We would like to thank F. Piuz for providing the detector and A. Braem for the production of the CsI photocathode. We are also grateful to the accelerator crew at GSI for the stable beam and the Gießen crew W. Döring, A. Rühl and J. Schneider for support.This work was supported in part by BMFT under contract No. 06 GI 475 I(3) and by GSI.