Gamma-aminobutyric Acid Treatment Research Articles

Gut microbiota remodeling drived by dietary millet protein prevents the metabolic syndrome

Metabolic syndrome (MetS) is a chronic disease associated with the disturbance of gut microbiota homeostasis. Metabolites derived from gut microbes play essential roles in MetS prevention and therapy. Here, we focused on the inhibitory effect of the extract of millet bran protein (EMBP) on a high-fat diet (HFD)-induced MetS, aiming to identify gut microbiota and their metabolites that involve in the anti-MetS activity of EMBP. The obesity, chronic inflammation, insulin resistance in MetS mouse models were abolished after EMBP treatment. The protective mechanism of EMBP against HFD-induced MetS may depend on improved gut barrier function. Using microbiome analysis, we found that EMBP supplementation improved gut microbiome dysbiosis in MetS mice, specifically upregulating Bacteroides acidifaciens. The fecal microbiota transplantation (FMT) also demonstrated this phenomenon. In addition, metabolomic analysis showed that EMBP mediates metabolic profiling reprogramming in MetS mice. Notably, a microbiota-derived metabolite, gamma-aminobutyric acid (GABA), is enriched by EMBP. In addition, exogenous GABA treatment produced a similar protective effect to EMBP by improving NRF2-dependent gut barrier function to protect HFD-induced MetS. The results suggest that EMBP suppress host MetS by remodeling of gut microbiota as an effective candidate for next-generation medicine food dual purpose dietary supplement to intervene in MetS.

Gamma-Aminobutyric Acid (GABA) Avoids Deterioration of Transport Water Quality, Regulates Plasma Biochemical Indices, Energy Metabolism, and Antioxidant Capacity of Tawny Puffer (Takifugui flavidus) under Transport Stress.

Live fish transportation is crucial for managing aquaculture but can pose health risks to fish due to stressors encountered during transportation. Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter that plays a crucial role in the central nervous system and is considered to exhibit anti-stress effects. This study aims to investigate the effects of GABA on the transport water quality, plasma biochemical indices, energy metabolism, and antioxidant capacity of tawny puffer (Takifugu flavidus) under transport stress. Tawny puffer were pretreated by immersing in aquariums containing GABA (final concentrations at 0, 5, 50, and 150 mg/L) seawater for 3 days; then, simulated transport was conducted using oxygen-filled polyethylene bags containing the same concentration of GABA seawater as the pretreatment period. Water samples, plasma, and liver were collected after 0, 6, and 12 h of transport. The results revealed that with the prolongation of transportation time, the control group's water quality deteriorated, stress-related plasma biochemical indices increased, glycolytic substrate contents decreased, glycolytic enzyme activities and product contents increased, and aerobic metabolic enzyme activities exhibited initial increases followed by declines, ATPase activities decreased, antioxidant enzyme activities decreased, and the lipid peroxidation marker contents increased. It is noteworthy that GABA treatment could avoid water quality deterioration during transportation, inhibit an elevation in stress-related biochemical indicators, regulate energy metabolism, and reduce oxidative damage in tawny puffer, especially at 50 and 150 mg/L concentrations. In summary, GABA treatment can effectively alleviate the transport stress of tawny puffer.

Gamma-aminobutyric acid for delaying type 1 diabetes mellitus: an update.

The current gold-standard management of hyperglycemia in individuals with type 1 diabetes mellitus (T1DM) is insulin therapy. However, this therapy is associated with a high incidence of complications, and delaying the onset of this disease produces a substantially positive impact on quality of life for individuals with a predisposition to T1DM, especially children. This review aimed to assess the use of gamma-aminobutyric acid (GABA) to delay the onset of T1DM in children. GABA produces protective and proliferative effects in 2 ways, β cell and immune cell modulation. Various in vitro and in vivo studies have shown that GABA induces proliferation of β cells, increases insulin levels, inhibits β-cell apoptosis, and suppresses T helper 1 cell activity against islet antigens. Oral GABA is safe as no serious adverse effects were reported in any of the studies included in this review. These findings demonstrate promising results for the use of GABA treatment to delay T1DM, specifically in genetically predisposed children, through immunoregulatory effects and the ability to induce β-cell proliferation.

Gamma-aminobutyric acid treatment promotes resistance against Sogatella furcifera in rice.

The Sogatella furcifera (Horváth) (Homoptera: Delphacidae) is a white-backed planthopper (WBPH) that causes "hopper burn" in rice, resulting in severe yield loss. Gamma-aminobutyric acid (GABA) is a well-known neurotransmitter that inhibits neurotransmission in insects by binding to specific receptors. In this study, we investigated the potential role of GABA in modulating rice resistance to WBPH and evaluated possible defense mechanisms. The experiment was conducted in green house in pots consist of four groups: control, GABA-treated, WBPH-infested, and WBPH-infested treated with GABA. Among the various tested concentration of GABA, 15 mM GABA was applied as a single treatment in water. The treatment was administered one week before WBPH infestation. The results revealed that 15 mM GABA treatment strongly increased WBPH resistance. A plate-based assay indicated that direct application of 15 mM GABA increased the mortality rate of WBPH and increased the damage recovery rate in rice plants. We found that GABA treatment increased the activation of antioxidant enzymes and reduced the reactive oxygen species content and malondialdehyde contents, and reduced the damage rate caused by WBPH. Interestingly, GABA-supplemented plants infested with WBPH exhibited increased phenylalanine ammonia-lyase and pathogenesis-related (PR) genes expression levels. GABA induced the accumulation of abscisic acid (ABA) and salicylic acid (SA) and enhanced the stomata closure and reduced leaf vessels to reduce water conductance during WBPH stress. Furthermore, we found that GABA application to the plant induced the expression of Jasmonic acid (JA) biosynthesis genes (LOX, AOS, AOC, and OPR) and melatonin biosynthesis-related genes (TDC, T5H, ASMT, and SNAT). Our study suggested that GABA increases resistance against WBPH infestation by regulating antioxidant defense system, TCA cycle regulation, phytohormonal signaling, and PR gene regulation.

Gamma-aminobutyric acid modulates antioxidant and osmoprotective systems in seedlings of Triticum aestivum cultivars differing in drought tolerance

The stress-protective effects of plant neurotransmitters, including gamma-aminobutyric acid (GABA) have been intensively examined in recent years. However, studies on the GABA influence on stress protective systems in bread wheat cultivars with different drought adaptation strategies are still lacking. The aim of this work was to estimate the GABA effect on the state of antioxidant and osmoprotective systems in etiolated seedlings of two wheat cultivars differing significantly in drought tolerance, namely Doskonala (non-drought-resistant) and Tobak (drought-resistant) under model drought induced by PEG 6000. Two-day-old seedlings were transferred to 15% PEG 6000 and incubated for two days in the absence or presence of GABA. Treatment with 0.1 and 0.5 mM GABA significantly reduced the growth-inhibitory effect of PEG 6000 on the roots and shoots of both cultivars, but to a greater extent on those of non-resistant Doskonala. It was shown that GABA treatment reduced drought-induced accumulation of H2O2 and MDA, stabilized SOD and GPX activity, the level of sugars, anthocyanins and flavonoids in seedlings of both cultivars. Meanwhile GABA treatment enhanced the stress-induced increase in proline content in the Doskonala cultivar, but decreased it in the Tobak, completely prevented stress induced decrease in anthocyanins and flavonoids level in the Tobak and only partially in Doskonala cultivar. Thus, the stabilization of the stress-protective systems functioning in the wheat cultivars and variety-dependent differences in response to GABA were revealed. Keywords: anthocyanins, antioxidant system, drought resistance, gamma-aminobutyric acid, oxidative stress, proline, Triticum aestivum

GABA regulates the proliferation and apoptosis of head and neck squamous cell carcinoma cells by promoting the expression of CCND2 and BCL2L1

Gamma-aminobutyric acid (GABA) is a multifunctional molecule that is widely present in the nervous system and nonneuronal tissues. It plays pivotal roles in neurotransmission, regulation of secretion, cell differentiation, proliferation, and tumorigenesis. However, the exact mechanisms of GABA in head and neck squamous cell carcinomas (HNSCCs) are unknown. We took advantage of RNA sequencing in this work and uncovered the potential gene expression profiles of the GABA-treated HNSCC cell line HN4–2. We found that the expression of CCND2 and BCL2L1 was significantly upregulated. Furthermore, GABA treatment inhibited the cell apoptosis induced by cisplatin and regulated the cell cycle after treatment with cisplatin in HN4–2 cells. Moreover, we also found that GABA could upregulate the expression of CCND2 and BCL2L1 after treatment with cisplatin. Our results not only reveal the potential pro-tumorigenic effect of GABA on HNSCCs but also provide a novel therapeutic target for HNSCC treatment.

GABA and Combined GABA with GAD65-Alum Treatment Alters Th1 Cytokine Responses of PBMCs from Children with Recent-Onset Type 1 Diabetes.

Type 1 diabetes (T1D) is an autoimmune disease culminating in the destruction of insulin-producing pancreatic cells. There is a need for the development of novel antigen-specific strategies to delay cell destruction, including combinatorial strategies that do not elicit systemic immunosuppression. Gamma-aminobutyric acid (GABA) is expressed by immune cells, β-cells, and gut bacteria and is immunomodulatory. Glutamic-acid decarboxylase 65 (GAD65), which catalyzes GABA from glutamate, is a T1D autoantigen. To test the efficacy of combinatorial GABA treatment with or without GAD65-immunization to dampen autoimmune responses, we enrolled recent-onset children with T1D in a one-year clinical trial (ClinicalTrials.gov NCT02002130) and examined T cell responses. We isolated peripheral blood mononuclear cells and evaluated cytokine responses following polyclonal activation and GAD65 rechallenge. Both GABA alone and GABA/GAD65-alum treatment inhibited Th1 cytokine responses over the 12-month study with both polyclonal and GAD65 restimulation. We also investigated whether patients with HLA-DR3-DQ2 and HLA-DR4-DQ8, the two highest-risk human leukocyte antigen (HLA) haplotypes in T1D, exhibited differences in response to GABA alone and GABA/GAD65-alum. HLA-DR4-DQ8 patients possessed a Th1-skewed response compared to HLA-DR3-DQ2 patients. We show that GABA and GABA/GAD65-alum present an attractive immunomodulatory treatment for children with T1D and that HLA haplotypes should be considered.

GABA treatment does not induce neogenesis of new endocrine cells from pancreatic ductal cells

ABSTRACT Previous studies indicated that ductal cells can contribute to endocrine neogenesis in adult rodents after alpha cells convert into beta cells. This can occur through Pax4 mis-expression in alpha cells or through long-term administration of gamma-aminobutyric acid (GABA) to healthy mice. GABA has also been reported to increase the number of beta cells through direct effects on their proliferation, but only in specific genetic mouse backgrounds. To test whether GABA induces neogenesis of beta cells from ductal cells or affects pancreatic cell proliferation, we administered GABA or saline over 2 or 6 months to Sox9CreER;R26RYFP mice in which 60–80% of large or small ducts were efficiently lineage labeled. We did not observe any increases in islet neogenesis from ductal cells between 1 and 2 months of age in saline treated mice, nor between 2 and 6 months of saline treatment, supporting previous studies indicating that adult ductal cells do not give rise to new endocrine cells during homeostasis. Unlike previous reports, we did not observe an increase in beta cell neogenesis after 2 or 6 months of GABA administration. Nor did we observe a significant increase in the pancreatic islet area, the number of insulin and glucagon double positive cells, or cell proliferation in the pancreas. This indicates that the effect of long term GABA administration on the pancreas is minimal or highly context dependent.

Gamma-Aminobutyric Acid Enhances Cadmium Phytoextraction by Coreopsis grandiflora by Remodeling the Rhizospheric Environment.

Gamma-aminobutyric acid (GABA) significantly affects plant responses to heavy metals in hydroponics or culture media, but its corresponding effects in plant-soil systems remain unknown. In this study, different GABA dosages (0-8 g kg-1) were added to the rhizosphere of Coreopsis grandiflora grown in Cd-contaminated soils. Cd accumulation in the shoots of C. grandiflora was enhanced by 38.9-159.5% by GABA in a dose-dependent approach because of accelerated Cd absorption and transport. The increase in exchangeable Cd transformed from Fe-Mn oxide and carbonate-bound Cd, which may be mainly driven by decreased soil pH rather than GABA itself, could be a determining factor responsible for this phenomenon. The N, P, and K availability was affected by multiple factors under GABA treatment, which may regulate Cd accommodation and accumulation in C. grandiflora. The rhizospheric environment dynamics remodeled the bacterial community composition, resulting in a decline in overall bacterial diversity and richness. However, several important plant growth-promoting rhizobacteria, especially Pseudomonas and Sphingomonas, were recruited under GABA treatment to assist Cd phytoextraction in C. grandiflora. This study reveals that GABA as a soil amendment remodels the rhizospheric environment (e.g., soil pH and rhizobacteria) to enhance Cd phytoextraction in plant-soil systems.

Comprehensive transcriptional and metabolomic analysis reveals the neuroprotective mechanism of dietary gamma-aminobutyric acid response to hypoxic stress in the Chinese mitten crab (Eriocheir sinensis)

Hypoxia is one of the serious stress challenges that aquatic animals face throughout their life. Our previous study found that hypoxia stress could induce neural excitotoxicity and neuronal apoptosis in Eriocheir sinensis, and observed that gamma-aminobutyric acid (GABA) has a positive neuroprotective effect on juvenile crabs under hypoxia. To reveal the neuroprotective pathway and metabolic regulatory mechanism of GABA in E. sinensis exposed to hypoxia stress, an 8-week feeding trial and acute hypoxia challenge were performed. Subsequently, we performed a comprehensive transcriptomic and metabolomic analysis of the thoracic ganglia of juvenile crabs. Differential genes and differential metabolites were co-annotated to 11 KEGG pathways, and further significant analysis showed that only the sphingolipid signaling pathway and the arachidonic acid metabolism pathway were significantly enriched. In the sphingolipid signaling pathway, GABA treatment significantly increased long-chain ceramide content in thoracic ganglia, which exerted neuroprotective effects by activating downstream signals to inhibit hypoxia-induced apoptosis. Moreover, in the arachidonic acid metabolism pathway, GABA could increase the content of neuroprotective active substances and reduce the content of harmful metabolites by regulating the metabolism of arachidonic acid for inflammatory regulation and neuroprotection. Furthermore, the decrease of glucose and lactate levels in the hemolymph suggests the positive role of GABA in metabolic regulation. This study reveals the neuroprotective pathways and possible mechanisms of GABA in juvenile E. sinensis exposed to hypoxia stress and inspires the discovery of new targets for improving hypoxia tolerance in aquatic animals.

Gamma-aminobutyric acid (GABA) suppresses hemocyte phagocytosis by binding to GABA receptors and modulating corresponding downstream pathways in blood clam, Tegillarca granosa

Although accumulating data demonstrated that gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, plays an important regulatory role in immunity of vertebrates, its immunomodulatory function and mechanisms of action remain poorly understood in invertebrates such as bivalve mollusks. In this study, the effect of GABA on phagocytic activity of hemocytes was evaluated in a commercial bivalve species, Tegillarca granosa. Furthermore, the potential regulatory mechanism underpinning was investigated by assessing potential downstream targets. Data obtained demonstrated that in vitro GABA incubation significantly constrained the phagocytic activity of hemocytes. In addition, the GABA-induced suppression of phagocytosis was markedly relieved by blocking of GABAA and GABAB receptors using corresponding antagonists. Hemocytes incubated with lipopolysaccharides (LPS) and GABA had significant higher K+-Cl- cotransporter 2 (KCC2) content compared to the control. In addition, GABA treatment led to an elevation in intracellular Cl−, which was shown to be leveled down to normal by blocking the ionotropic GABAA receptor. Treatment with GABAA receptor antagonist also rescued the suppression of GABAA receptor-associated protein (GABARAP), KCC, TNF receptor associated factor 6 (TRAF6), inhibitor of nuclear factor kappa-B kinase subunit alpha (IKKα), and nuclear factor kappa B subunit 1 (NFκB) caused by GABA incubation. Furthermore, incubation of hemocytes with GABA resulted in a decrease in cAMP content, an increase in intracellular Ca2+, and downregulation of cAMP-dependent protein kinase (PKA), calmodulin kinase II (CAMK2), calmodulin (CaM), calcineurin (CaN), TRAF6, IKKα, and NFκB. All these above-mentioned changes were found to be evidently relieved by blocking the metabotropic G-protein-coupled GABAB receptor. Our results suggest GABA may play an inhibitory role on phagocytosis through binding to both GABAA and GABAB receptors, and subsequently regulating corresponding downstream pathways in bivalve invertebrates.

Gamma-Aminobutyric Acid Promotes Beige Adipocyte Reconstruction by Modulating the Gut Microbiota in Obese Mice.

Given the increasing prevalence of obesity, the white-to-beige adipocyte conversion has attracted interest as a target for obesity treatment. Gamma-aminobutyric acid (GABA) treatment can reduce obesity, but the underlying mechanism remains unclear. Here, we aimed to investigate the mechanism by which GABA triggers weight loss by improving the beiging of inguinal white adipose tissue (iWAT) and the role of gut microbiota in this process. The results showed that GABA reduced body weight and adipose inflammation and promoted the expression of thermogenic genes in the iWAT. The 16S rRNA sequence analysis of gut microbiota showed that GABA treatment increased the relative abundance of Bacteroidetes, Akkermansia, and Romboutsia and reduced that of Firmicutes and Erysipelatoclostridium in obese mice. Additionally, serum metabolomic analysis revealed that GABA treatment increased 3-hydroxybutyrate and reduced oxidized lipid levels in obese mice. Spearman's correlation analysis showed that Akkermansia and Romboutsia were negatively associated with the levels of oxidized lipids. Fecal microbiota transplantation analysis confirmed that the gut microbiota was involved in the white-to-beige adipocyte reconstruction by GABA. Overall, our findings suggest that GABA treatment may promote iWAT beiging through the gut microbiota in obese mice. GABA may be utilized to protect obese people against metabolic abnormalities brought on by obesity and gut dysbiosis.

GABA increases susceptibility to DSS-induced colitis in mice

• GABA fails to induce significant colitis within colons of healthy mice. • GABA facilitates susceptibility to DSS-induced colitis and impairs the intestinal barrier. • GABA inhibits colonic epithelium proliferation and promotes its apoptosis. Gamma-aminobutyric acid (GABA) is an important inhibitory neurotransmitter. Recently, it is considered to be a bioactive molecule with various health benefits. Ulcerative colitis (UC) is a chronic inflammatory disorder. An intestinal barrier defect is considered as one of the key events in the pathogenesis of UC. However, the issue of whether GABA is involved with intestinal inflammation remains debatable. In the present study, we investigated the effects of GABA on intestinal barrier function in healthy mice and susceptibility to UC in a dextran sulphate sodium (DSS) mouse model. Our results indicate that GABA treatment fails to induce significant colitis in healthy mice, however, GABA treatment enhances susceptibility to DSS-induced colitis in mice. Further, our results revealed GABA induces an intestinal barrier defect by inhibiting colonic epithelium proliferation and promoting its apoptosis. Accordingly, use of GABA treatment as applied for human health requires careful consideration.

A GABA-receptor agonist reduces pneumonitis severity, viral load, and death rate in SARS-CoV-2-infected mice.

Gamma-aminobutyric acid (GABA) and GABA-receptors (GABA-Rs) form a major neurotransmitter system in the brain. GABA-Rs are also expressed by 1) cells of the innate and adaptive immune system and act to inhibit their inflammatory activities, and 2) lung epithelial cells and GABA-R agonists/potentiators have been observed to limit acute lung injuries. These biological properties suggest that GABA-R agonists may have potential for treating COVID-19. We previously reported that GABA-R agonist treatments protected mice from severe disease induced by infection with a lethal mouse coronavirus (MHV-1). Because MHV-1 targets different cellular receptors and is biologically distinct from SARS-CoV-2, we sought to test GABA therapy in K18-hACE2 mice which develop severe pneumonitis with high lethality following SARS-CoV-2 infection. We observed that GABA treatment initiated immediately after SARS-CoV-2 infection, or 2 days later near the peak of lung viral load, reduced pneumonitis severity and death rates in K18-hACE2 mice. GABA-treated mice had reduced lung viral loads and displayed shifts in their serum cytokine/chemokine levels that are associated with better outcomes in COVID-19 patients. Thus, GABA-R activation had multiple effects that are also desirable for the treatment of COVID-19. The protective effects of GABA against two very different beta coronaviruses (SARS-CoV-2 and MHV-1) suggest that it may provide a generalizable off-the-shelf therapy to help treat diseases induced by new SARS-CoV-2 variants and novel coronaviruses that evade immune responses and antiviral medications. GABA is inexpensive, safe for human use, and stable at room temperature, making it an attractive candidate for testing in clinical trials. We also discuss the potential of GABA-R agonists for limiting COVID-19-associated neuroinflammation.

Physiological and proteomic analyses of γ-aminobutyric acid (GABA)-treated tubers reveals that StPOD42 promotes sprouting in potato

Gamma-aminobutyric acid (GABA) is a nonproteinogenic amino acid that plays vital roles in plant growth and developmental processes. However, its role in regulating potato sprouting is unknown. Therefore, the physiological and molecular mechanisms underlying the sprouting process were assessed, and we found that GABA promoted sprouting after treatment for 50 d. In addition, the GABA and soluble sugar contents increased while the starch content decreased. To study the molecular mechanism by which exogenous GABA accelerates tuber sprouting, comparative proteomic analysis of tuber bud eyes was performed after GABA treatment for 48 h. Further analysis revealed 316 differentially abundant proteins (DAPs) that are mainly involved in fatty acid and sugar metabolism and cutin, suberin and wax biosyntheses. The qRT‒PCR results suggested that the GABA transaminase 2 (GABA-T2) and GABA-T3 expression levels showed the greatest decrease at 30 d of storage. Peroxidase 42 (StPOD42) expression showed the greatest increase at 30 d. Overexpression of StPOD42 in potato was found to promote tuber sprouting. Our results provide new insights into the role of GABA in regulating the sprouting process and indicate that StPOD42 is a target gene for molecular breeding to modulate potato sprouting.

Molecular Cloning of a TCHQD Class Glutathione S-Transferase and GST Function in Response to GABA Induction of Melon Seedlings under Root Hypoxic Stress

Glutathione-S-transferase (GST), a versatile enzyme that occurs widely in plants, plays a key role in plant resistance to environmental stresses. Previous results have demonstrated that GST proteins are involved in alleviating root hypoxic injury caused by gamma-aminobutyric acid (GABA); however, the induction mechanism of the GST gene in the melon under root hypoxic stress and its functional mechanisms remain unclear. In this study, based on gene cloning and bioinformatics analysis, GST gene expression and activity and glutathione (GSH) content were assessed under root hypoxic and normoxic conditions with or without GABA. The results showed that the CmGST locus includes an 804 bp gene sequence that encodes 267 amino acids. The sequence was highly similar to those of other plant TCHQD GSTs, and the highest value (94%) corresponded to Cucumis sativus. Real-time PCR results showed that the CmGST gene was induced by root hypoxic stress and GABA, and this induction was accompanied by increased GST activity and GSH content. Root hypoxic stress significantly upregulated CmGST expression in melon roots (0.5–6 d), stems, and leaves (0.5–4 d), and GST activity and GSH content were also significantly increased. Exogenous GABA treatment upregulated CmGST gene expression, GST activity, and GSH content, particularly under root hypoxic conditions. As a result, CmGST expression in GABA-treated roots and leaves at 0.5–4 d and stems at 0.5–6 d was significantly higher than that under root hypoxic stress alone. This study provides evidence that the TCHQD CmGST may play a vital role in how GABA increases melon hypoxia tolerance by upregulating gene expression and improving metabolism.

Schistosomicidal and hepatoprotective activity of gamma-aminobutyric acid (GABA) alone or combined with praziquantel against Schistosoma mansoni infection in murine model

ObjectiveThis study aimed to evaluate the efficacy of gamma-aminobutyric acid (GABA) alone or combined with praziquantel (PZQ) against Schistosoma (S) mansoni infection in a murine model. MethodsFive groups, 8 mice each, were studied; GI served as normal controls; GII: S. mansoni-infected control group and the other three S. mansoni-infected groups received drug regimens for 5 consecutive days as follows GIII: Infected-PZQ treated group (200 mg/kg/day); GIV: Infected-GABA treated group (300 mg/kg/day) and GV: Infected-PZQ-GABA treated group (100 mg/kg/day for each drug). All animal groups were sacrificed two weeks later and different parasitological, histopathological and biochemical parameters were assessed. ResultsCombined GABA-PZQ treated group recorded the highest significant reduction in all parasitological, histopathological and biochemical parameters followed by PZQ and finally GABA groups. Combined GABA-PZQ treatment led to the complete disappearance of immature eggs and marked reduction of deposited eggs in liver tissues and improved liver pathology. Significant improvement in hepatic oxidative stress levels, serum albumin and total protein in response to GABA treatment alone or combined with PZQ. ConclusionGABA had schistosomicidal, hepatoprotective and antioxidant activities against S. mansoni infection, GABA disrupted parasite pairing and activity, reduced the total number of worms recovered and the number of ova in the tissues. GABA may be considered an adjuvant therapy to potentiate PZQ antiparasitic activity and eradicate infection-induced liver damage and oxidative stress.

Gamma-aminobutyric acid coupled with copper ion stress stimulates lipid production of green microalga Monoraphidium sp. QLY-1 through multiple mechanisms

Induction of copper ion (Cu2+) stress is a method used to increase lipid accumulation in microalgae, but it decreases cell growth. In this work, the impacts of gamma-aminobutyric acid (GABA) coupled with Cu2+ stress on the biomass and oil yield in Monoraphidium sp. QLY-1 were investigated. Results suggested that the combined treatment of GABA and Cu2+ resulted in a higher lipid content (55.13%) than Cu2+ treatment (48.43%). Furthermore, GABA addition upregulated the levels of lipid-relevant genes, cellular GABA, ethylene (ETH), and antioxidant enzyme activities and alleviated oxidative damage caused by Cu2+ stress. The autophagy-relevant gene atg8 was also upregulated by GABA treatment. Further exploration indicated that cell autophagy induced the lipid content up to 58.09% with GABA and Cu2+ stress treatment. This investigation demonstrates that the coupling strategy can stimulate lipid production and shed light on the underlying mechanisms in lipid biosynthesis, cell autophagy, and stress response of microalgae.

GABA induces a hormonal counter-regulatory response in subjects with long-standing type 1 diabetes

IntroductionExperimentally, gamma-aminobutyric acid (GABA) has been found to exert immune-modulatory effects and induce beta-cell regeneration, which make it a highly interesting substance candidate for the treatment of type 1 diabetes...

Gamma-aminobutyric acid improves phenanthrene phytotoxicity tolerance in cucumber through the glutathione-dependent system of antioxidant defense

Phenanthrene (PHE), a typical organic pollutant, has drawn attention in recent years due to its toxicity to plants and human health. Gamma-aminobutyric acid (GABA) induce plant tolerance to diverse stresses. However, the role and regulatory mechanisms of GABA in PHE stress responses in plants remains largely uncharacterized. Here, we showed that GABA content increased by 44.5%, 89.2%, 160% and 39.2% under 50, 100, 200 and 300 µM PHE treatment, respectively compared with mock. GABA treatment alleviated PHE-induced growth inhibition in a dose-dependent manner, with the most effective concentration of 50 mM GABA. Although exogenous GABA could not influence the accumulation of PHE in cucumber, it significantly mitigated photosynthetic inhibition and enhanced the transcripts and activities of the antioxidant enzymes such as ascorbate peroxidase (APX), catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD), resulting in less accumulation of hydrogen peroxide (H2O2) and superoxide (O2.–). Importantly, timecourse analyses of glutathione (GSH) homeostasis showed that GABA markedly increased GSH content and GR activity as well as the transcripts of GSH biosynthesis-related genes GSH1, GSH2 and GR during PHE stress. Conversely, pretreatment with GSH biosynthesis inhibitor buthionine sulfoximine (BSO) abolished the GABA-induced changes in PHE stress. Together, these results suggest that GABA enhances tolerance to PHE stress via a GSH-dependent system of antioxidant defense in cucumber.