Facilitating the gut brain axis by probiotic bacteria to modulate neuroimmune response on lead exposed zebra fish models

Unravelling the efficacy of gut biome has a major impact on health. An unbalanced microbiome composition is linked to many common illnesses such as gut dysbiosis, mental deformities and immunological imbalance. An optimistic influence on the gut biome can be made by consumingprobiotics. This would stimulate neuroprotection and immunomodulation intended by heavy metals pollution. Lead is a major source of neurotoxin that can induce neural deformities. Lactobacillusspecies isolated from curd were characterized to confirm its specificity. Zebra fish was reared at standard conditions and preclinical assessment on the intensity of induced neurotoxin lead was performed. The embryo toxic assay, immunomodulation effects and animal behavioural models endorsed the consequence of neurotoxicity. Different concentrations of bacterial isolate with standard antidepressant was considered for analysing the vigour of toxicity and its influence on cognitive behaviour by novel tank diving method. The restrain in the animal behaviour was also conferred by all the test samples with a decreased bottom dwelling time which was authenticated with haematology and histopathological studies. The alterations in morphology of the lymphocytes were balanced by the treated test samples. This study paves a twofold potential of probiotic as neuroprotectant and immune modulator against heavy metal toxicity.

Relative profiling of L-tryptophan derivatives from selected edible mushrooms as psychoactive nutraceuticals to inhibit P-glycoprotein: a paradigm to contest blood-brain barrier.

Depression is a mental illness and is considered to be a global threat. It is designated as burden of disease. There is therefore an intense need to improve the therapeutic response of antidepressants. India beholds a wide fraction (Agaricus bisporus and Pleurotus ostreatus ) as a vital source of non-hallucinogenic indole compounds. The amino acids L-tryptophan and 5-hydroxytryptophan (5-HTP) are precursors of serotonin. 5-HTP is a potential antidepressant that can cross the blood-brain barrier (BBB) at a high rate and is converted into serotonin more efficiently. Drug delivery across this blockade remains a challenge due to the stimulation of efflux pump receptors called permeability glycoprotein (P-gp). This work reports a comparative phytochemical assay and profiling of non-hallucinogenic tryptophan metabolites using HPLC from two organic extracts of edible mushrooms. The efficacy of the eluted compounds was authenticated as P-gp inhibitors with in vitro and in silico studies. The following four derivatives were obtained from the methanol and ethanol extracts of the mushrooms: 5-hydroxy-L-tryptophan (5HTR), 5-hydroxy tryptamine (5-HT), L-tryptophan (L-Trp), and tryptamine (TA). In vitro and molecular docking studies targeting P-gp (minimum energy: -64.38 and -83.93 kcal/mol, respectively) substantiated the ability of mushroom-derived metabolites to facilitate drug delivery in the brain. This study verified that mushrooms containing non-hallucinogenic metabolites can act as psychoactive nutraceuticals that are significant for enhancing mental health. The high therapeutic efficacy, these mushrooms can serve as ideal neurological drug leads to fortify treatment for mental illness.

Analysing the antidepressant and drug efflux competence of Clitoria ternateaL. as P-glycoprotein inhibitor to facilitate blood brain barrier

Clitoria ternateaL. is a vital ayurvedic herbfeatured with a wide spectrum of mental health benefits. The present study investigates the competence of the plant against depression and to inhibit the membrane efflux protein P-glycoprotein (P-gp) that can regulate and restrict drug permeation into the brain. Antidepressant competence of the aqueous plant extract was assessed by animal despair studies on depression induced female mice models. The P-glycoprotein inhibitory potential of active phytocompounds was evaluated by molecular docking assay and substantiated by a cell line study. The in vivostudies exhibited a significant difference in the immobility time thereby establishing antidepressant activity. The histopathological sections from cortex region of treated brain showed decreased degenerative changes. Ten imperative phytocompounds facilitated docking complexes against P-glycoprotein among which Kaempferol 3-O-(2״,6״-di-O-rhamnopyranosyl) glucopyranoside exhibited a finest docking score of -12.569 kcal mol-1. Conversely it was attested by the rhodamine transport assay that demonstrated the inhibitory potential to surpass blood brain barrier. The outcome of the study endorses the efficacy of Clitoria ternateaL. as an idyllic brain drug and facilitates brain permeability.