Search Results (19)

The gut microbiota and its interaction with the nervous system through the gut–brain axis (MGB) have been the subject of growing interest in biomedical research. It has been proposed that modulation of microbiota using probiotics could offer a promising therapeutic alternative for mood regulation and the treatment of anxiety and depression disorders. The findings indicate that several probiotic strains, such as Lactobacillus and Bifidobacterium, have demonstrated anxiolytic and antidepressant effects in pre and clinical studies. These effects seem to be mediated by the regulation of the hypothalamic–pituitary–adrenal axis (HPA), the synthesis of neurotransmitters such as serotonin (5-HT) and Gamma-amino-butyric acid (GABA), as well as the modulation of systemic inflammation. However, the lack of standardization in dosing and strain selection, in addition to the scarcity of large-scale clinical studies, limit the applicability of these findings in clinical therapy. Additional research is required to establish standardized therapeutic protocols and better understand the role of probiotics in mental health. The aim of this narrative review is to discuss the relationship between the gut microbiota and the MGB axis in the context of anxiety and depression disorders, the underlying neurobiological mechanisms, as well as the preclinical evidence for the effect of probiotics in modulating these disorders. In this way, an exhaustive search was carried out in scientific databases including PubMed, ScienceDirect, Scopus, and Web of Science. Preclinical research evaluating the effects of different probiotic strains in animal models during chronic treatment was selected, excluding those studies that did not provide access to the full text. Full article

The genotypic diversity and genome-wide association study (GWAS) of potato proteins and amino acid content were investigated in two environments: 98 potato accessions in Environment I and 93 in Environment II. Results revealed that aspartic acid was the most abundant amino acid in environment I and glutamic acid in environment II. The limiting amino acids were cysteine in both environments. The environmental variance accounted for more than 40% of the total variance for all traits except for serine and gamma amino butyric acid (GABA), indicating that potato protein and most amino acids were affected by growing seasons. GWAS identified 78 significant loci associated with potato protein and amino acid contents. The pleiotropic loci, especially those located on chromosomes 6, 9, and 11, provide a strong genetic basis for quality improvement. This study provides genetic insights into potato proteins and amino acid diversity, thereby enhancing molecular breeding for nutritional qualities. Full article

Gabapentin (GBP) was originally developed as a potential agonist for Gamma-Amino-Butyric-Acid (GABA) receptors, aiming to inhibit the activation of pain-signaling neurons. Contrary to initial expectations, it does not bind to GABA receptors. Instead, it exhibits several distinct pharmacological activities, including: (1) binding to the alpha-2-delta protein subunit of voltage-gated calcium channels in the central nervous system, thereby blocking the excitatory influx of calcium; (2) reducing the expression and phosphorylation of CaMKII via modulation of ERK1/2 phosphorylation; (3) inhibiting glutamate release and interfering with the activation of NMDA receptors; (4) enhancing GABA synthesis; (5) increasing cell-surface expression of δGABA_A receptors, contributing to its antinociceptive, anticonvulsant, and anxiolytic-like effects. Additionally, GBP displays (6) inhibition of NF-kB activation and subsequent production of inflammatory cytokines, and (7) stimulation of the purinergic adenosine A1 receptor, which supports its anti-inflammatory and wound-healing properties. Initially approved for treating seizures and postherpetic neuralgia, GBP is now broadly used for various conditions, including psychiatric disorders, acute and chronic neuropathic pain, and sleep disturbances. Recently, as an eye drop formulation, it has also been explored as a therapeutic option for ocular surface discomfort in conditions such as dry eye, neurotrophic keratitis, corneal ulcers, and neuropathic ocular pain. This review aims to summarize the evidence supporting the molecular effects of GBP, with a special emphasis on its applications in ocular surface diseases. Full article

Drosophila suzukii, an invasive insect pest, poses a significant threat to various fruit crops. The use of broad-spectrum insecticides to control this pest can reduce the effectiveness of biological control agents, such as the parasitoid Trichopria anastrephae. Here, we evaluated the toxicity of newly synthesized lactone derivatives on D. suzukii and their selectivity towards T. anastrephae. We used in silico approaches to identify potential targets from the most promising molecules in the D. suzukii nervous system and to understand potential differences in susceptibilities between D. suzukii and its parasitoid. Of the nine molecules tested, (rac)-8 and compound 4 demonstrated efficacy against the fly. Exposure to the estimated LC₉₀ of (rac)-8 and compound 4 resulted in a mortality rate of less than 20% for T. anastrephae without impairing the parasitoid’s functional parasitism. The in silico predictions suggest that (rac)-8 and compound 4 target gamma amino butyric acid (GABA) receptors and transient receptor potential (TRP) channels of D. suzukii. However, only the reduced interaction with TRP channels in T. anastrephae demonstrated a potential reason for the selectivity of these compounds on the parasitoid. Our findings suggest the potential for integrating (rac)-8 and compound 4 into D. suzukii management practices. Full article

Baked goods manufacturing parameters and fermentation conditions interfere with the nutrients content and affect their gastrointestinal fate. Pinsa Romana is a type of pizza that, recently, has been commercially rediscovered and that needed elucidation from a nutritional and digestibility perspective. In this study, six types of Pinsa Romana (five made with indirect method and one produced with straight dough technology) were characterized for their biochemical and nutritional features. Several variables like indirect (biga) Pinsa Romana production process, fermentation time and use of sourdough were investigated. The Pinsa Romana made with biga including sourdough and fermented for 48 h at 16 °C ((PR_48(SD)) resulted in the lowest predicted glycemic index, in the highest content of total peptides, total and individual free amino acids and gamma-amino butyric acid (GABA), and in the best protein quality indexes (protein efficiency ratio and nutritional index). The static in vitro digestion showed that the digesta from PR_48(SD) confirmed a reduced in vitro glycemic response after intake, and it showed a lower bioavailability of hydrophilic peptides. Furthermore, the inclusion of sourdough in biga enhanced the bioavailability of protein-related end-products including human health promoting compounds such as essential amino acids. Full article

The dysbiosis of intestinal microbiota and their metabolites is linked to the occurrence and development of metabolic syndrome. Although fructose has been proven to be associated with worsened mucus in the colon, its mechanism remains unclear. In this study, we evaluated the relatively low intake of sucrose and fructose in the experimental colitis of Sprague Dawley rats by investigating the microbiome and metabolome. Results showed that sucrose and fructose significantly reduced body weight, colon length and increased inflammation infiltration in colon. Sucrose and fructose worsen colon functions by inhibiting the expression of tight junction (TJ) protein ZO-1 and increasing the level of lipopolysaccharide neoandrographolide (LPS) in plasma, while fructose was more significant. Furthermore, sucrose and fructose significantly changed the composition of gut microbiota characterized by decreasing Adlercreutzia, Leuconostoc, Lactococcus and Oscillospira and increasing Allobaculum and Holdemania along with reducing histidine, phenylalanine, arginine, glycine, aspartic acid, serine, methionine valine, alanine, lysine, isoleucine, leucine, threonine, tryptophan, tyrosine, proline, citrulline, 4-hydroxyproline and gamma amino butyric acid (GABA). Metabolome results showed that fructose may aggravate experimental colitis symptoms by inducing amino metabolism dysbiosis in the colon. These findings suggested that fructose worsened colitis by manipulating the crosstalk between gut microbiota and their metabolites. Full article

Gamma amino butyric acid (GABA), an important free amino acid in plant tissues, plays an essential role in all stages of plant growth and development. In this study, we aimed to explore the effects of GABA on the nutrient absorption of loquat [Eriobotrya japonica (Thunb.) Lindl.] seedlings. The effects of applying exogenous GABA in different concentrations (0.0, 0.5, 1.0, 1.5, and 2 g L⁻¹) on the nutrient uptake of loquat seedlings were studied. GABA increased the biomass (dry weight) and contents of photosynthetic pigments in loquat seedlings to a certain extent. GABA concentration exhibited a quadratic polynomial regression relationship with the biomass. Exogenous GABA in different concentrations increased the total nitrogen (N) and phosphorus (P) contents in loquat seedlings, whereas only 0.5 and 1.0 g L⁻¹ of GABA increased the potassium (K) content. Similarly, GABA concentration also had a polynomial regression relationship with the total N, P, and K contents. Compared to the control, 0.5, 1.0, 1.5, and 2.0 g L⁻¹ of GABA increased the shoot total N content by 27.30, 32.99, 15.41, and 12.93%, respectively, and also increased the shoot total P content by 26.12, 37.52, 21.99, and 9.61%, respectively. Furthermore, correlation and grey relational analyses showed that the carotenoid content, root biomass, and soil alkali-hydrolyzable N concentration were the indicators most closely associated with the uptakes of N, P, and K in shoots. This study shows that exogenous GABA can promote the growth and nutrient uptake of loquat seedlings at an optimum concentration of 1.0 g L⁻¹. Full article

Microbial metabolites affect the neuron system and muscle cell functions. Amyotrophic lateral sclerosis (ALS) is a multifactorial neuromuscular disease. Our previous study has demonstrated elevated intestinal inflammation and dysfunction of the microbiome in patients with ALS and an ALS mouse model (human-SOD1^G93A transgenic mice). However, the metabolites in ALS progression are unknown. Using an unbiased global metabolomic measurement and targeted measurement, we investigated the longitudinal changes of fecal metabolites in SOD1^G93A mice over the course of 13 weeks. We further compared the changes of metabolites and inflammatory response in age-matched wild-type (WT) and SOD1^G93A mice treated with the bacterial product butyrate. We found changes in carbohydrate levels, amino acid metabolism, and the formation of gamma-glutamyl amino acids. Shifts in several microbially contributed catabolites of aromatic amino acids agree with butyrate-induced changes in the composition of the gut microbiome. Declines in gamma-glutamyl amino acids in feces may stem from differential expression of gamma-glutamyltransferase (GGT) in response to butyrate administration. Due to the signaling nature of amino acid-derived metabolites, these changes indicate changes in inflammation, e.g., histamine, and contribute to differences in systemic levels of neurotransmitters, e.g., γ-Aminobutyric acid (GABA) and glutamate. Butyrate treatment was able to restore some of the healthy metabolites in ALS mice. Moreover, microglia in the spinal cord were measured by IBA1 staining. Butyrate treatment significantly suppressed the IBA1 level in the SOD1^G93A mice. Serum IL-17 and LPS were significantly reduced in the butyrate-treated SOD1^G93A mice. We have demonstrated an inter-organ communications link among microbial metabolites, neuroactive metabolites from the gut, and inflammation in ALS progression. The study supports the potential to use metabolites as ALS hallmarks and for treatment. Full article

Gamma-amino butyric acid (GABA) is well known to help elevate pancreatic β cell vitality and insulin levels in blood. GABA works via a coupling with GABA receptors; thus, the concentration of GABA_A receptors on the plasma membrane of β cells appears to be critical for insulin regulation. Various medical conditions, such as pediatric and adult obstructive sleep apnea (OSA), show high levels of Type 2 diabetes; such patients also are exposed to intermittent hypoxia (IH), which modifies the GABA levels. To evaluate the potential therapeutic roles of GABA for diabetic patients with OSA, we studied the interactions of IH with GABA and GABA_A receptors in young rats. Using rat pups and primary pancreatic islets, we evaluated the roles of GABA in insulin secretion. We show that GABA effectively increased the insulin secretion of pancreatic islets under normal ambient oxygen levels, as well as in culture medium with a glucose level of 2 mM. GABA also increased islet insulin secretion conditioned under IH in a 16 mM glucose medium. When islets were IH-treated, insulin secretion decreased due to lower intracellular chloride levels in accordance with the increased KCC2 levels. The results show that IH challenges down-regulate the GABA_A receptor levels in pancreatic islets, which decreases GABA–GABA_A receptor coupling action, as well as membrane depolarization for insulin secretion. The findings have the potential to suggest novel interventions for insulin regulation during IH of disordered breathing, including OSA. Full article

Although the benefits of the consumption of green tea and its components, including catechins and theanine, regarding aging, memory impairment and age-related cognitive decline have been investigated in senescence-accelerated prone mice (SAMP8), studies that simultaneously measured the kinds of proteins that vary in their expression due to the administration of green tea and its extracts were not found. In this study, the effect of dietary and decaffeinated matcha on protein expression in the hippocampus of SAMP 8 was examined comprehensively, mainly using proteomics. Although improvements in memory and the hair appearance of the back coat were limited upon administering the samples, the following regulations were observed in some of the proteins involved in neuron degeneration, Parkinson’s and Alzheimer’s diseases, synapse transmission and nerve cell plasticity, antioxidation, glutamate transport and metabolism, GABA (γ-amino butyric acid) formation and transport and excitatory amino acid transporters: proteins downregulated upon sample intake (p < 0.05): brain acid-soluble protein 1, microtubule-associated protein tau, synapsin-2, sodium- and chloride-dependent GABA transporter; proteins that tended to decrease upon sample intake (0.05 < p < 0.10): Parkinson’s disease (autosomal recessive and early-onset) 7 and synapsin-1; proteins upregulated upon sample intake (p > 0.95): glutathione S-transferase Mu 1, tubulin alpha-1A chain, dynamin-2, calcium/calmodulin-dependent protein kinase type II subunit gamma and tyrosine 3-monooxygenase/tyrosine 5-monooxygenase activation protein epsilon polypeptide; proteins that tended to increase upon sample intake (0.95 > p > 0.90): glutathione S-transferase Mu7 and soluble carrier family 1 (glial high-affinity glutamate transporter); proteins that tended to decrease: sodium- and chloride-dependent GABA transporter 3. These results indicate that matcha and decaffeinated matcha could reduce aging and cognitive impairment by regulating the expression of these proteins. Furthermore, these proteins could be used as markers for the evaluation of food and its available components for reducing aging and cognitive impairment. Full article

Obesity and diabetes mellitus have become the surprising menaces of relative economic well-being worldwide. Gamma amino butyric acid (GABA) has a prominent role in the control of blood glucose, energy homeostasis as well as food intake at several levels of regulation. The effects of GABA in the body are exerted through ionotropic GABA_A and metabotropic GABA_B receptors. This treatise will focus on the pharmacologic targeting of GABA_A receptors to reap beneficial therapeutic effects in diabetes mellitus and obesity. A new crop of drugs selectively targeting GABA_A receptors has been under investigation for efficacy in stroke recovery and cognitive deficits associated with schizophrenia. Although these trials have produced mixed outcomes the compounds are safe to use in humans. Preclinical evidence is summarized here to support the rationale of testing some of these compounds in diabetic patients receiving insulin in order to achieve better control of blood glucose levels and to combat the decline of cognitive performance. Potential therapeutic benefits could be achieved (i) By resetting the hypoglycemic counter-regulatory response; (ii) Through trophic actions on pancreatic islets, (iii) By the mobilization of antioxidant defence mechanisms in the brain. Furthermore, preclinical proof-of-concept work, as well as clinical trials that apply the novel GABA_A compounds in eating disorders, e.g., olanzapine-induced weight-gain, also appear warranted. Full article

Gamma-amino butyric acid (GABA) is marketed in the U.S. as a dietary supplement. USP conducted a comprehensive safety evaluation of GABA by assessing clinical studies, adverse event information, and toxicology data. Clinical studies investigated the effect of pure GABA as a dietary supplement or as a natural constituent of fermented milk or soy matrices. Data showed no serious adverse events associated with GABA at intakes up to 18 g/d for 4 days and in longer studies at intakes of 120 mg/d for 12 weeks. Some studies showed that GABA was associated with a transient and moderate drop in blood pressure (<10% change). No studies were available on effects of GABA during pregnancy and lactation, and no case reports or spontaneous adverse events associated with GABA were found. Chronic administration of GABA to rats and dogs at doses up to 1 g/kg/day showed no signs of toxicity. Because some studies showed that GABA was associated with decreases in blood pressure, it is conceivable that concurrent use of GABA with anti-hypertensive medications could increase risk of hypotension. Caution is advised for pregnant and lactating women since GABA can affect neurotransmitters and the endocrine system, i.e., increases in growth hormone and prolactin levels. Full article

The purpose of this study was to develop a formulation of Sunsik with improved health benefits by adding germinated wheat (GW) and herbal plant extract (HPE) using a response surface methodology (RSM). The central composite experimental design (CCD) was used to evaluate the effects of Sunsik with added HPE (2–4%) and GW (10–20%) on total phenolic content (TPC), total flavonoid content (TFC), Trolox equivalent antioxidant capacity (TEAC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity, gamma butyric acid (GABA) content, total color changes (△E), browning index (BI), water absorption index (WAI), and water solubility index (WSI). As a result of the CCD, the independent and dependent variables were fitted by the second-order polynomial equation, and the lack of fit for response surface models was not significant except in relation to WSI. The GABA content, TPC, and TEAC were more adequate for a linear model than for a quadratic model, and they might be affected by GW rather than HPE. Alternatively, the TFC, DPPH radical scavenging capacity, WAI, WSI, △E, and BI were fitted with quadratic models. The optimum formulation that could improve antioxidant and physicochemical properties was Sunsik with 3.5% and 20% added HPE and GW, respectively. Full article

Whole kiwifruit (‘Hayward’ and ‘Zesy002’) were examined for their bioaminergic potential after being subjected to in vitro gastrointestinal digestion and colonic fermentation. Controls included the prebiotic inulin and water, a carbohydrate-free vehicle. The dopamine precursor l-dihydroxyphenylalanine (L-DOPA) and the serotonin precursor 5-hydroxytryptophan were increased in the kiwifruit gastrointestinal digesta (‘Hayward’ > ‘Zesy002’) in comparison to the water digesta. Fermentation of the digesta with human fecal bacteria for 18 h modulated the concentrations of bioamine metabolites. The most notable were the significant increases in L-DOPA (‘Zesy002’ > ‘Hayward’) and γ-aminobutyric acid (GABA) (‘Hayward’ > ‘Zesy002’). Kiwifruit increased Bifidobacterium spp. and Veillonellaceae (correlating with L-DOPA increase), and Lachnospira spp. (correlating with GABA). The digesta and fermenta were incubated with Caco-2 cells for 3 h followed by gene expression analysis. Effects were seen on genes related to serotonin synthesis/re-uptake/conversion to melatonin, gut tight junction, inflammation and circadian rhythm with different digesta and fermenta from the four treatments. These indicate potential effects of the substrates and the microbially generated organic acid and bioamine metabolites on intestinal functions that have physiological relevance. Further studies are required to confirm the potential bioaminergic effects of gut microbiota–kiwifruit interactions. Full article

Nicotine causes tobacco dependence, which may result in fatal respiratory diseases. The striatum is a key structure of forebrain basal nuclei associated with nicotine dependence. In the striatum, glutamate release is increased when α7 nicotinic acetylcholine receptors expressed in the glutamatergic terminals are exposed to nicotine, and over-stimulates glutamate receptors in gamma amino-butyric acid (GABA)ergic neurons. These receptor over-stimulations in turn potentiate GABAergic outputs to forebrain basal nuclei and contribute to the increase in psychomotor behaviors associated with nicotine dependence. In parallel with glutamate increases, nicotine exposure elevates brain-derived neurotrophic factor (BDNF) release through anterograde and retrograde targeting of the synapses of glutamatergic terminals and GABAergic neurons. This article reviews nicotine-exposure induced elevations of glutamatergic neurotransmission, the bidirectional targeting of BDNF in the striatum, and the potential regulatory role played by BDNF in behavioral responses to nicotine exposure. Full article