Allyl isothiocyanate, a TRPA1 agonist, protects against olanzapine-induced hypothalamic and hepatic metabolic aberrations in female mice.

Olanzapine, a widely prescribed atypical antipsychotic, poses a great risk to the patient's health by fabricating a plethora of severe metabolic and cardiovascular adverse effects eventually reducing life expectancy and patient compliance. Its heterogenous receptor binding profile has made it difficult to point out a specific cause or treatment for the related side effects. Growing body of evidence suggest that transient receptor potential (TRP) channel subfamily Ankyrin 1 (TRPA1) has pivotal role in pathogenesis of type 2 diabetes and obesity. With this background, we aimed to investigate the role of pharmacological manipulations of TRPA1 channels in antipsychotic (olanzapine)-induced metabolic alterations in female mice using allyl isothiocyanate (AITC) and HC-030031 (TRPA1 agonist and antagonist, respectively). It was found that after 6 weeks of treatment, AITC prevented olanzapine-induced alterations in body weight and adiposity; serum, and liver inflammatory markers; glucose and lipid metabolism; and hypothalamic appetite regulation, nutrient sensing, inflammatory and TRPA1 channel signaling regulating genes. Furthermore, several of these effects were absent in the presence of HC-030031 (TRPA1 antagonist) indicating protective role of TRPA1 agonism in attenuating olanzapine-induced metabolic alterations. Supplementary in-depth studies are required to study TRPA1 channel effect on other aspects of olanzapine-induced metabolic alterations.

Immunomodulatory action of synbiotic comprising of newly isolated lactic acid producing bacterial strains against allergic asthma in mice.

Given the reported role of gut-microbiota in asthma pathogenesis, the present work was carried to evaluate immunomodulatory action of newly isolated lactic acid producing bacterial strains Bifidobacterium breve Bif11 and Lactiplantibacillus plantarum LAB31 against asthma using ovalbumin (OVA) based mouse model. Our results show that both strains modulate Th2 immune response potentially through production of short chain fatty acids (SCFAs), resulting in suppression of OVA-induced airway inflammation. Furthermore, synbiotic comprising of both strains and prebiotic, Isomaltooligosaccharide exhibited superior potential in amelioration of OVA-induced airway inflammation through improved modulation of Th2 immune response. Further, synbiotic protects against OVA-induced mucus hyper-production and airway-hyperresponsiveness. Such protection was associated with normalization of gut microbiome and enhanced production of SCFAs in cecum which correlates closely with population of T-regulatory cells in spleen. Overall, our novel synbiotic possesses the ability to fine-tune the immune response for providing protection against allergic asthma.

Short-chain fatty acids increase intracellular calcium levels and enhance gut hormone release from STC-1 cells via transient receptor potential Ankyrin1.

Short-chain fatty acids (SCFAs), metabolites of colonic bacterial fermentation of complex carbohydrates, are closely related to the release of gut hormones. In this study, we examined the involvement of transient receptor potential ankyrin 1 (TRPA1) in SCFA-induced increase in intracellular calcium ([Ca2+ ]i ) and its impact on gut hormone secretion using naturally TRPA1 expressing intestinal secretin tumour cell-1 (STC-1) cell line. Individual SCFAs and their physiological mix enhanced calcium influx in TRPA1-dependent manner. SCFA mix also significantly increased membrane expression of TRPA1. Gene expression studies revealed that SCFA mix elevated the expression of genes involved in calcium-activated calcineurin pathway in TRPA1-dependent manner and cAMP-regulated transcriptional co-activators (CRTC) pathway independent to TRPA1. Genes representing synaptic vesicular exocytosis and gut hormone precursors were significantly elevated with SCFA mix treatment. Treatment with TRPA1 antagonist HC-030031 markedly reduced these effects. The release of gut hormones was elevated with 10 mm SCFA mix in TRPA1 dependent manner. Our in vivo prebiotic study results suggested presence of an environment conducive to increase in gut hormone secretion. Overall, our findings provide an evidence for the possible role of TRPA1 in SCFA-induced increase in gut hormone secretion, hence another mechanism of action for prebiotics.

Production of surfactant and detergent-stable, halophilic, and alkalitolerant alpha-amylase by a moderately halophilic Bacillus sp. Strain TSCVKK.

A moderately halophilic alkalitolerant Bacillus sp. Strain TSCVKK, with an ability to produce extracellular halophilic, alkalitolerant, surfactant, and detergent-stable alpha-amylase was isolated from soil samples obtained from a salt-manufacturing industry in Chennai. The culture conditions for higher amylase production were optimized with respect to NaCl, substrate, pH, and temperature. Maximum amylase production of 592 mU/ml was achieved in the medium at 48 h with 10% NaCl, 1% dextrin, 0.4% yeast extract, 0.2% tryptone, and 0.2% CaCl(2) at pH 8.0 at 30 degrees C. The enzyme activity in the culture supernatant was highest with 10% NaCl at pH 7.5 and 55 degrees C. The amylase that was partially purified by acetone precipitation was highly stable in various surfactants and detergents. Glucose, maltose, and maltooligosaccharides were the main end products of starch hydrolysis indicating that it is an alpha-amylase.