Celiac Disease and Possible Dietary Interventions: From Enzymes and Probiotics to Postbiotics and Viruses.

Celiac Disease (CeD) is a chronic small intestinal immune-mediated enteropathy caused by the ingestion of dietary gluten proteins in genetically susceptible individuals. CeD is one of the most common autoimmune diseases, affecting around 1.4% of the population globally. To date, the only acceptable treatment for CeD is strict, lifelong adherence to a gluten-free diet (GFD). However, in some cases, GFD does not alter gluten-induced symptoms. In addition, strict adherence to a GFD reduces patients' quality of life and is often a socio-economic burden. This narrative review offers an interdisciplinary overview of CeD pathomechanism and the limitations of GFD, focusing on current research on possible dietary interventions. It concentrates on the recent research on the degradation of gluten through enzymes, the modulation of the microbiome, and the different types of "biotics" strategies, from probiotics to the less explored "viromebiotics" as possible beneficial complementary interventions for CeD management. The final aim is to set the context for future research that may consider the role of gluten proteins and the microbiome in nutritional and non-pharmacological interventions for CeD beyond the sole use of the GFD.

Metabolite profiling of arginase inhibitor activity guided fraction of Ficus religiosa leaves by LC-HRMS.

Cardiovascular disease is one of the major causes of deaths worldwide. Increased arginase activity is associated with cardiovascular disease. The literature shows that plants are a good source of arginase inhibitors. Hence in the present work arginase inhibitor activity is studied from Ficus religiosa leaves. A fine powder of F. religiosa leaves was serially extracted in various solvents, viz. hexane, chloroform, ethyl acetate and methanol. Out of those four solvent extracts, the one showing highest arginase inhibitor activity was loaded onto the column for further fractionation. Among the collected fractions, the one showing the highest activity was subjected to identification of metabolites by using LC-HRMS. Total compounds including acipimox, edoxudine, levulinic acid, hydroxyhydroquinone, ramiprilglucuronide, berberine, antimycin A, swietenine and some short peptides were identified from the fraction showing the highest arginase inhibitory activity. Identification of these metabolites from F. religiosa and their biological importance may help to promote its use as medicinal plant. Further purification and characterization of therapeutically novel molecules will be the subject of future work.

Significant Hydrolysis of Wheat Gliadin by Bacillus tequilensis (10bT/HQ223107): a Pilot Study.

Peptidase therapy is suggested to be effective to minimize gliadin toxicity in celiac disease (CD). Hence, present study deals with gliadin-hydrolysing peptidases. The efficient peptidase from the Bacillus tequilensis was purified using ammonium sulfate fractionation and preparative electrophoresis. Analysis of in-solution and in-gel hydrolysis of gliadin using one and two-dimensional SDS-PAGE revealed nearly complete hydrolysis of gliadin peptides after 180 min of incubation with B. tequilensis protease. Purified peptidase was found to be stable at acidic (pH 3.5) to neutral (pH 7.2) pH range. The molecular mass and isoelectric point of the peptidase were observed around 29 kDa and 5.2, respectively. The internal protein sequence obtained through mass spectrometric analysis suggested that peptidase might belong to peptidase S9 family known for prolyl-specific peptidases. This study recommends the possible applicability of this peptidase for elimination of immunotoxic gliadin peptides and may prove useful in CD treatment.

A bifunctional α-amylase/trypsin inhibitor from pigeonpea seeds: Purification, biochemical characterization and its bio-efficacy against Helicoverpa armigera.

This paper evaluates α-amylase inhibitor (α-AI) mediated defense of pigeonpea against Helicoverpa armigera. A bifunctional α-amylase/trypsin inhibitor was purified from the seeds of pigeonpea by native liquid phase isoelectric focusing (N-LP-IEF), affinity chromatography and preparative electrophoresis. Its in-vivo and in-vitro interaction with midgut amylases of H. armigera was studied along with growth inhibitory activity. One and two dimensional (2D) zymographic analyses revealed that the purified inhibitor is dimeric glycoprotein (60.2kDa and 56kDa) exist in a multi-isomeric form with five pI variants (pI 5.5 to 6.3). It was found to be heat labile with complete inactivation up to 80°C and stable over a wide range of pH (4-11). The slow binding and competitive type of α-amylase inhibition was observed with 0.08µM of dissociation constant (Ki) for the enzyme-inhibitor complex (EI). The internal protein sequence of two subunits obtained by mass spectrometry matched with cereal-type α-AI, a conserved domain from AAI_LTSS superfamily and sialyltransferase-like protein respectively. In-vivo studies indicated up-regulation of total midgut α-amylase activity with negative effect on growth rate of H. armigera suggesting its suitability for pest control.

A facile synthesis of 5,5-dideutero-4-dimethyl(phenyl)silyl-6-undecyl-tetrahydropyran-2-one as a deuterium labeled synthon for (-)-tetrahydrolipstatin and (+)-δ-hexadecanolide.

Deuterium-labeled biologically active compounds are gaining importance because they can be utilized as tracers or surrogate compounds to understand the mechanism of action, absorption, distribution, metabolism, and excretion. Deuterated drug molecules (heavy drugs) become novel as well as popular because of better stability and bioavailability compared with their hydrogen analogs. Labeling of organic molecules with deuterium at specific positions is thus gaining popularity. In this work, we have exploited a highly regioselective and enantioselective direct Michael addition of methyl-d3 alkyl ketones to dimethyl(phenyl)silylmethylene malonate that was catalyzed by (S)-N-(2-pyrrolidinylmethyl)pyrrolidine/trifluoroacetic acid/ D2 O combination with high yield and isotopic purity. The 5,5-dideutero-4-dimethyl(phenyl)silyl-6-undecyl-tetrahydropyran-2-one was obtained from the adduct of methyl-d3 undecanyl ketone and dimethyl(phenyl)silylmethylene malonate by a silicon controlled diastereoselective ketone reduction, lactonization, and deethoxycarbonylation. The dideuterated silylated tetrahydropyran-2-one is the precursor for geminal (2) H2 -labeled (+)-4-hydroxy-6-undecyl-tetrahydropyran-2-one, an advanced intermediate for gem-dideutero (-)-tetrahydrolipstatin and (+)-δ-hexadecanolide syntheses.