Structural Basis of Artemisinin Binding Sites in Serum Albumin with the Combined Use of NMR and Docking Calculations.

Artemisinin is known to bind to the main plasma protein carrier serum albumin (SA); however, there are no atomic level structural data regarding its binding mode with serum albumin. Herein, we employed a combined strategy of saturation transfer difference (STD), transfer nuclear Overhauser effect spectroscopy (TR-NOESY), STD-total correlation spectroscopy (STD-TOCSY), and Interligand Noes for PHArmacophore Mapping (INPHARMA) NMR methods and molecular docking calculations to investigate the structural basis of the interaction of artemisinin with human and bovine serum albumin (HSA/BSA). A significant number of inter-ligand NOEs between artemisinin and the drugs warfarin and ibuprofen as well as docking calculations were interpreted in terms of competitive binding modes of artemisinin in the warfarin (FA7) and ibuprofen (FA4) binding sites.

Analytical and Structural Tools of Lipid Hydroperoxides: Present State and Future Perspectives.

Mono- and polyunsaturated lipids are particularly susceptible to peroxidation, which results in the formation of lipid hydroperoxides (LOOHs) as primary nonradical-reaction products. LOOHs may undergo degradation to various products that have been implicated in vital biological reactions, and thus in the pathogenesis of various diseases. The structure elucidation and qualitative and quantitative analysis of lipid hydroperoxides are therefore of great importance.

Production of hydroxytyrosol rich extract from Olea europaea leaf with enhanced biological activity using immobilized enzyme reactors.

As olive leaves constitute the main by-product of the olive oil industry with important environmental and economic impact, there is an increasing demand for its valorization. In the present work, we report the development and application of immobilized enzyme batch bioreactors for the chemo-enzymatic treatment of an aqueous Olea europaea leaf extract rich in oleuropein to produce an extract enriched in hydroxytyrosol and other oleuropein hydrolysis products. To this end, a robust biocatalyst was developed through the immobilization of β-glucosidase on chitosan-coated magnetic beads which exhibited high hydrolytic stability after 240 h of incubation at 37 °C.

Simultaneous determination of artemisinin and its analogs and flavonoids in Artemisia annua crude extracts with the use of NMR spectroscopy.

Artemisia annua is a promising and potent antimalarial herbal drug. This activity has been ascribed to its component artemisinin, a sesquiterpene lactone. The ability to determine artemisinin and its known analogs in plant extracts is an especially difficult task because the compounds are present in low concentrations, are thermolabile, and lack ultraviolet or fluorescent chromophores.

Ethyl Acetate Extract of Origanum vulgare L. ssp. hirtum Prevents Streptozotocin-Induced Diabetes in C57BL/6 Mice.

Type 1 diabetes (T1D) is an autoimmune disease that develops as a consequence of pancreatic β-cell death induced by proinflammatory mediators. Because Origanum vulgare L. ssp.

Deconvoluting the Dual Antiplatelet Activity of a Plant Extract.

A thorough evaluation of the antiplatelet activity profile of hexane olive leaf extract in human platelets indicated a potent activity accomplished through a two axis inhibition of platelet activation triggered both by ADP and thrombin. To delineate the extract components responsible for this dual activity, an NMR based method was established to determine and quantify the triterpenoid content leading to the characterization of uvaol, erythrodiol, and oleanolic acid. The antiplatelet profile of the total extract and of the 3 determined triterpenoids was evaluated against in vitro platelet aggregation induced by several platelet agonists as also on PAC-1 binding and P-selectin membrane expression both in healthy volunteers and in platelets from patients with an acute coronary syndrome receiving dual antiplatelet therapy with aspirin and ticagrelor.

Rosemary tea consumption results to anxiolytic- and anti-depressant-like behavior of adult male mice and inhibits all cerebral area and liver cholinesterase activity; phytochemical investigation and in silico studies.

Our aim was to investigate the possible effects of regular drinking of Rosmarinus officinalis L. leaf infusion on behavior and on AChE activity of mice. Rosemary tea (2% w/w) phytochemical profile was investigated through LC/DAD/ESI-MS(n).

Methanolic extract of Origanum vulgare ameliorates type 1 diabetes through antioxidant, anti-inflammatory and anti-apoptotic activity.

Type 1 diabetes (T1D), an autoimmune inflammatory disorder, develops as a consequence of pancreatic β-cell destruction and results in hyperglycaemia. Since current T1D therapy mainly involves insulin replacement, the aim of the present study was to evaluate the therapeutic potential of Origanum vulgare L. ssp.

Temporal transcriptome changes induced by methyl jasmonate in Salvia sclarea.

Salvia sclarea is a traditional medicinal and aromatic plant that grows in Europe and produces various economically important compounds, including phenylpropanoid derivatives and terpenoids. Methyl jasmonate (MeJA) is commonly used to elicit plant stress responses. However, how MeJA enhances production of secondary metabolites in S.

1H-NMR as a structural and analytical tool of intra- and intermolecular hydrogen bonds of phenol-containing natural products and model compounds.

Experimental parameters that influence the resolution of 1H-NMR phenol OH signals are critically evaluated with emphasis on the effects of pH, temperature and nature of the solvents. Extremely sharp peaks (Δν1/2≤2 Hz) can be obtained under optimized experimental conditions which allow the application of 1H-13C HMBC-NMR experiments to reveal long range coupling constants of hydroxyl protons and, thus, to provide unequivocal assignment of the OH signals even in cases of complex polyphenol natural products. Intramolecular and intermolecular hydrogen bonds have a very significant effect on 1H OH chemical shifts which cover a region from 4.

Investigation of solute-solvent interactions in phenol compounds: accurate ab initio calculations of solvent effects on 1H NMR chemical shifts.

Accurate (1)H chemical shifts of the -OH groups of polyphenol compounds can be calculated, compared to experimental values, using a combination of DFT, polarizable continuum model (PCM) and discrete solute-solvent hydrogen bond interactions. The study focuses on three molecular solutes: phenol, 4-methylcatechol and the natural product genkwanin in DMSO, acetone, acetonitrile, and chloroform. Excellent linear correlation between experimental and computed chemical shifts (with the GIAO method at the DFT/B3LYP/6-311++G(2d,p) level) was obtained with minimization of the solvation complexes at the DFT/B3LYP/6-31+G(d) and DFT/B3LYP/6-311++G(d,p) level of theory with a correlation coefficient of 0.

Olive leaf extracts are a natural source of advanced glycation end product inhibitors.

Advanced glycation end products (AGEs), which are readily formed and accumulated with sustained hyperglycemia, contribute to the development of diabetic complications. As a consequence, inhibition of AGE formation constitutes an attractive therapeutic/preventive target. In the current study, we explored the phytochemical composition and the in vitro effect of two different olive leaf extracts (an aqueous and a methanolic) on AGE formation.

Hydrogen bonding probes of phenol -OH groups.

Correlations between hydrogen bonds and solvent effects on phenol -OH proton shieldings, temperature coefficients (Δδ/ΔT) and effects on OH diffusion coefficients for numerous phenolic acids, flavonols, flavones, and oleuropein derivatives of biological interest were investigated in several organic solvents and were shown to serve as reliable indicators of hydrogen bonding and solvation state of -OH groups. The temperature coefficients span a range of -0.5 to -12.

Phytochemical profile of Rosmarinus officinalis and Salvia officinalis extracts and correlation to their antioxidant and anti-proliferative activity.

The goal of this study was to monitor the anti-proliferative activity of Rosmarinus officinalis and Salvia officinalis extracts against cancer cells and to correlate this activity with their phytochemical profiles using liquid chromatography/diode array detection/electrospray ion trap tandem mass spectrometry (LC/DAD/ESI-MS(n)). For the quantitative estimation of triterpenic acids in the crude extracts an NMR based methodology was used and compared with the HPLC measurements, both applied for the first time, for the case of betulinic acid. Both extracts exerted cytotoxic activity through dose-dependent impairment of viability and mitochondrial activity of rat insulinoma m5F (RINm5F) cells.

Exploration of the antiplatelet activity profile of betulinic acid on human platelets.

Betulinic acid, a natural pentacyclic triterpene acid, presents a diverse mode of biological actions including antiretroviral, antibacterial, antimalarial, and anti-inflammatory activities. The potency of betulinic acid as an inhibitor of human platelet activation was evaluated, and its antiplatelet profile against in vitro platelet aggregation, induced by several platelet agonists (adenosine diphosphate, thrombin receptor activator peptide-14, and arachidonic acid), was explored. Flow cytometric analysis was performed to examine the effect of betulinic acid on P-selectin membrane expression and PAC-1 binding to activated platelets.

Phytochemical composition of "mountain tea" from Sideritis clandestina subsp. clandestina and evaluation of its behavioral and oxidant/antioxidant effects on adult mice.

Purpose: The goals of this study were to monitor the effect of drinking of herbal tea from Sideritis clandestina subsp. clandestina for 6 weeks on behavioral and oxidant/antioxidant parameters of adult male mice and also to evaluate its phytochemical composition.

Methods: The phytochemical profile of the Sideritis tea was determined by liquid chromatography-UV diode array coupled to ion-trap mass spectrometry with electrospray ionization interface.

Phenolic compounds and antioxidant activity of olive leaf extracts.

The total phenolic content and antioxidant activities of olive leaf extracts were determined. Plant material was extracted with methanol and fractionated with solvents of increasing polarity, giving certain extracts. The qualitative changes in the composition of the extracts were determined after the storage of leaves for 22 h at 37°C, before the extraction.

Rapid and novel discrimination and quantification of oleanolic and ursolic acids in complex plant extracts using two-dimensional nuclear magnetic resonance spectroscopy-Comparison with HPLC methods.

A novel strategy for NMR analysis of mixtures of oleanolic and ursolic acids that occur in natural products is described. These important phytochemicals have similar structure and their discrimination and quantification is rather difficult. We report herein the combined use of proton-carbon heteronuclear single-quantum coherence ((1)H-(13)C HSQC) and proton-carbon heteronuclear multiple-bond correlation ((1)H-(13)C HMBC) NMR spectroscopy, in the identification and quantitation of oleanolic acid (OA) and ursolic acid (UA)in plant extracts of the Lamiaceae and Oleaceae family.