The identification of a novel SIRT6 modulator from Trigonella foenum-graecum using ligand fishing with protein coated magnetic beads.

SIRT6 is a histone deacetylase that has been proposed as a potential therapeutic target for metabolic disorders and the prevention of age-associated diseases. Thus the identification of compounds that modulate SIRT6 activity could be of great therapeutic importance. We have previously developed an H3K9 deacetylation guided assay with SIRT6 coated magnetic beads (SIRT6-MB). With the developed assay, we identified quercetin, naringenin and vitexin as SIRT6 inhibitors from T. foenum-graecum seed extract using a candidate approach. Currently, the predominant method for the identification of active compounds from a plant extract is carried out through a dereplication process. A novel targeted approach for the direct identification of active compounds from a complex matrix could save time and resources. Herein, we report the application of the SIRT6-MB for 'fishing' experiments utilizing T. foenum-graecum seed extract. In which orientin, and seventeen other compounds were identified as SIRT6 binders. This is the first use of this method for 'fishing' out active ligands from a botanical matrix, and sets the basis for the identification of active compounds from a complex matrix.

Seahorses - a source of traditional medicine.

Wild marine organisms have been used in the discovery and development of traditional and allopathic medical treatments for a long time. Seahorses, a syngnathidae fish, are one of the important candidate organisms which have been used in Chinese traditional medicine from time immemorial. It is believed that seahorses have the potential to cure infertility, baldness, asthma and arthritis. An authentic research work on the biomedical validation of seahorses proved that they have the ability to cure arthritis and its associated inflammation. A Cathepsin-derived peptide from the seahorse species of Hippocampus kuda proved to be effective in chondrocyte cells and its associated impaired arthritis inflammation. Apart from this, seahorses have a putative free radical scavenging effect in controlling the ageing process. More authentic research is needed in order to validate the biomedical potential. This article highlights the role of seahorses' value in traditional medicine and their biomedical properties.

Effect of selected antiasthmatic plant constituents against micro organism causing upper respiratory tract infection.

Most exacerbations of asthma can be proven to be associated with bacterial infections and there is scientific evidence that frequent respiratory infections particularly bacterial infections provoke asthma attack. Considering these facts different plant extracts and phytoconstituents with proven anti asthmatic property had been selected for screening anti microbial activity in in-vitro models. In the present study, Coleus forskohlii Willd. extract (10% Forskolin), Piper Longum L. Extract (20% Piperine), Adathoda vasica Nees. extract (30% Vasicinone), Curcuma longa L. extract (60% Curcumin) were screened for the antibacterial activity against human pathogens causing upper respiratory infection namely Haemophilus influenzae , Streptococcus pneumoniae , Streptococcus pyrogene and Staphylococcus aureus, by taking Gentamycin, Optochin, Bacitracin and Amoxicillin as reference standards. Except for Adathoda vasica Nees. extract, all the other selected plant extracts exhibited a moderate activity antibacterial activity against selected strains.

Invitro antioxidant activity of selected antiasthmatic herbal constituents.

Asthmatic patients are more subjected to continuous oxidative stress. Roosting the antioxidant defenses of asthma patient could be beneficial as it may help thwart symptoms of the lung disease and asthma. Considering these facts different plant extracts and phytoconstituents with proven anti asthmatic property had been subjected to antioxidant study at various combinations using Diphenyl Vicryl Hydrazyl radical scavenging method, Hydrogen Peroxide radical scavenging method, Nitric oxide radical inhibition method, ABTS radical scavenging method and Lipid peroxidation assay method.All the selected herbal based constituents and extracts at different combination showed a potent antioxidant activiy by Nitric oxide radical inhibition activiy method followed by ABTS method. The present finding suggests that the selected plant based anti asthmatic constituents namely Coleus extract (10% Forskolin), Piper longum extract (20% Piperine), CurcuminC3Complex (60% Curcumin), Vasaka (30% Vasicinone), Forskolin (95%), Pperine (98%), Curcumin C3 Complex (98.5%) and Vasicinone (75%) could be utilised in alternate anti asthmatic therapy, since they play a vital role in scavenging Nitric oxide which could prevent the bronchial inflammation in asthmatic patients.

Is there a role for magnetic resonance imaging in diagnosing colovesical fistulas?

OBJECTIVES: Colovesical fistula is a devastating complication, usually secondary to diverticulitis or colon cancer. Imaging plays a crucial role in delineating the underlying anatomy and identifying an etiologic factor. Barium enema, computed tomography, and cystoscopy have been the mainstays of investigation, but they have less than ideal sensitivity and specificity. This study assessed the role of magnetic resonance imaging (MRI) in the investigation of patients with probable colovesical fistulas. METHODS: A total of 22 patients with presentations suspicious for enterovesical fistulas who underwent evaluation with axial T(1)-weighted and axial, coronal, and sagittal T(2)-weighted 1.5T MRI (body-phased array) were identified. Of the 22 patients, 19 underwent laparotomy and repair. RESULTS: MRI correctly identified the presence of a fistula and defined the underlying etiology in 18 of 19 patients. Colovesical fistula was correctly excluded in 1 of 19 patients. The remaining 3 patients were either unfit for surgery or refused. CONCLUSIONS: The results of our study have shown that MRI is an accurate method of evaluating patients with suspicion of colovesical fistulas, identifying the anatomy of the tract, as well as the etiology. This is not only useful for diagnosis, but also for surgical planning.

Pharmacophore modelling of stereoselective binding to the human organic cation transporter (hOCT1).

BACKGROUND AND PURPOSE: The human organic cation transporter-1 (hOCT1) is a polyspecific transporter that plays a role in drug distribution, metabolism and excretion. Previous studies have demonstrated that hOCT1 binding can be stereoselective, but the mechanism for stereochemical recognition has not been described. The purpose of this study was to develop a pharmacophore model to describe stereoselective binding to hOCT1. EXPERIMENTAL APPROACH: A set of 22 compounds including 8 pairs of enantiomers and five pairs of diastereomers was used to develop a pharmacophore model. The pharmacophore modeling was carried out using Catalyst version 4.11 and HypoGen and was based upon the correlation of the structures and activities (K(i) values) of the compounds used in the study. KEY RESULTS: The resulting model contained a positive ion, hydrophobic and two hydrogen-bond acceptor interaction sites. The relative enantioselectivity of 8/8 enantiomeric pairs and diastereoselectivity of 5/5 diastereomers was described by mapping to a combination of at least 3 of the 4 functional feature sites of the model. CONCLUSIONS AND IMPLICATIONS: The pharmacophore model describes stereoselective interactions with hOCT1 at one of the binding sites on the molecule.

Cryocrystallography of a Kunitz-type serine protease inhibitor: the 90 K structure of winged bean chymotrypsin inhibitor (WCI) at 2.13 A resolution.

The crystal structure of a Kunitz-type double-headed alpha--chymotrypsin inhibitor from winged bean seeds has been refined at 2.13 A resolution using data collected from cryo-cooled (90 K) crystals which belong to the hexagonal space group P6(1)22 with unit-cell parameters a = b = 60.84, c = 207.91 A. The volume of the unit cell is reduced by 5.3% on cooling. The refinement converged to an R value of 20.0% (R(free) = 25.8%) for 11100 unique reflections and the model shows good stereochemistry, with r.m.s. deviations from ideal values for bond lengths and bond angles of 0.011 A and 1.4 degrees, respectively. The structural architecture of the protein consists of 12 antiparallel beta-strands joined in the form of a characteristic beta-trefoil fold, with the two reactive-site regions, Asn38-Leu43 and Gln63-Phe68, situated on two external loops. Although the overall protein fold is the same as that of the room-temperature model, some conformational changes are observed in the loop regions and in the side chains of a few surface residues. A total of 176 ordered water molecules and five sulfate ions are included in the model.