Effects Of Γ-aminobutyric Acid Research Articles

Effects of γ-aminobutyric acid (GABA) intake in combination with exercise on muscle strength in humans with decreased mobility: a randomized, double-blind, placebo-controlled, parallel-group study

Background: Aging-related declines in skeletal muscle mass, muscle strength, and physical function are related to instability, falls, and frailty in older people, resulting in the need for nursing care. Objective: To investigate the effect of oral γ-aminobutyric acid (GABA) intake and exercise on muscle parameters in healthy subjects whose muscle strength is beginning to decline with age. Methods: A randomized, double-blind, placebo-controlled, parallel-group comparative study was conducted. Fifty subjects (over 40 years old) were randomly divided into the GABA (100 mg/day) or placebo food intake group. Subjects orally consumed the respective study substance every day for 12 weeks. They performed daily “locomotion training” as devised by the Japanese Orthopedic Society. Muscle mass, fat mass, and knee extension muscle strength were measured. Results: The two groups had no significant differences in muscle and fat mass. Compared with the placebo food group, the GABA group showed a significant improvement in knee extension muscle strength in the left and right legs at pre-dose Week 0 (at Week 6, p = 0.02). In post hoc subgroup analysis by sex, when compared with the placebo food intake group, the GABA food intake group showed significant improvement in knee extension muscle strength of the right leg at Weeks 6 (p = 0.001) and 12 (p = 0.007), the left leg at Week 6 (p = 0.02), the stronger of the left and right legs at pre-dose Week 0 (at Week 6, p = 0.001), and the weaker of the left and right legs at pre-dose Week 0 (at Week 12, p = 0.013) in males. Conclusions: These results suggest that GABA intake combined with daily exercise is effective for maintaining knee extension muscle strength, which decreases with age. Furthermore, there were no safety issues with the intake of GABA-containing food during this study. Trial registration: UMIN-CTR: UMIN000050152. Keywords: γ-Aminobutyric acid, GABA, Muscle mass, Knee extension muscle strength, Aging

Effect of γ-Aminobutyric Acid on Patients with Refractory Epilepsy

Effect of γ-Aminobutyric Acid on Patients with Refractory Epilepsy

γ-Aminobutyric acid is involved in overlapping pathways against chilling injury by modulating glutamate decarboxylase and defense responses in papaya fruit.

The effect of γ-aminobutyric acid (GABA) treatment at two concentrations (1 mM or 5 mM) on papaya fruit stored at 4°C and 80%-90% relative humidity for 5 weeks was investigated. The application of GABA at 5 mM apparently inhibited chilling injury, internal browning, electrolyte leakage, malondialdehyde (MDA), hydrogen peroxide (H2O2), polyphenol oxidase (PPO), phospholipase D (PLD), and lipoxygenase (LOX) activities of papaya fruit. Fruit treated with 5 mM GABA enhanced the activities of ascorbate peroxidase (APX), catalase (CAT), glutathione reductase (GR), superoxide dismutase (SOD), glutamate decarboxylase (GAD), and phenylalanine ammonia-lyase (PAL). In addition, GABA treatment significantly displayed higher levels of proline, endogenous GABA accumulation, phenolic contents, and total antioxidant activity than the nontreated papaya. The results suggested that GABA treatment may be a useful approach to improving the chilling tolerance of papaya fruit by reducing oxidative stress and enhancing the defense system.

GABA Application Enhances Drought Stress Tolerance in Wheat Seedlings (Triticum aestivum L.).

In this study, the effects of γ-aminobutyric acid (GABA) on physio-biochemical metabolism, phenolic acid accumulation, and antioxidant system enhancement in germinated wheat under drought stress was investigated. The results showed that exogenous GABA reduced the oxidative damage in wheat seedlings caused by drought stress and enhanced the content of phenolics, with 1.0 mM being the most effective concentration. Six phenolic acids were detected in bound form, including p-hydroxybenzoic acid, vanillic acid, syringic acid, p-coumaric acid, ferulic acid, and sinapic acid. However, only syringic acid and p-coumaric acid were found in free form. A total of 1.0 mM of GABA enhanced the content of total phenolic acids by 28% and 22%, respectively, compared with that of drought stress, on day four and day six of germination. The activities of phenylalanine ammonia lyase (PAL), cinnamic acid 4-hydroxylase (C4H) and 4-coumarate coenzyme A ligase (4CL) were activated by drought stress plus GABA treatment. Antioxidant enzyme activities were also induced. These results indicate that GABA treatment may be an effective way to relieve drought stress as it activates the antioxidant system of plants by inducing the accumulation of phenolics and the increase in antioxidant enzyme activity.

γ-Aminobutyric acid treatment induced chilling tolerance in postharvest kiwifruit (Actinidia chinensis cv. Hongyang) via regulating ascorbic acid metabolism

The effect of γ-Aminobutyric acid (GABA) treatment on ascorbic acid (AsA) metabolism and chilling injury in postharvest kiwifruit was studied. The results revealed that kiwifruit treated with GABA displayed higher chilling tolerance and better quality maintenance as compared to the controls. Higher AsA was observed in GABA-treated fruit which was beneficial to cell membrane protection and damage alleviation against chilling mediated oxidative stress. Gene expression analysis found the increased expression of AsA anabolic and regenerative genes and down-regulation of its catabolic genes together could contribute to the elevation of AsA levels in kiwifruit after GABA treatment. In addition, the transcripts of several candidate transcription factors such as bHLHs and HZ1 involved in AsA biosynthesis were also enhanced by GABA treatment. Collectively, our results indicated that GABA induced chilling tolerance in postharvest kiwifruit due to the higher AsA content by positively regulating ascorbate metabolic genes and candidate transcription factors.

Effects of γ-aminobutyric acid on freshness and processing properties of eggs during storage

Effects of γ-aminobutyric acid (GABA) on egg storage properties were investigated by comparing freshness and processing properties between eggs treated with different GABA concentrations and untreated controls. GABA treatment delayed storage-associated increases of albumen pH value and surface hydrophobicity and decreases of protein index, yolk index, Haugh unit (HU) value, albumen height, solubility, gel hardness, and apparent viscosity. Highest HU, yolk index, and emulsion stability values and peak storage performance were observed after injection of eggs with 0.05 mL of GABA (0.3 g/mL). Even after 25 days of storage, GABA-treated eggs exhibited freshness resembling that of fresh eggs, indicating that GABA treatment extended shelf life by 10 days relative to controls. Peak solubility, emulsifying activity, emulsifying stability, foaming capacity, and foaming stability values of 89.74%, 0.72, 14.18, 43.35, and 45.57, respectively, for GABA-treated eggs exceeded corresponding control group values, thus demonstrating that GABA treatment of eggs slowed storage-related deterioration of freshness and processing quality.

The Effects of GABA-Rich Adzuki Beans on Glycolipid Metabolism, as Well as Intestinal Flora, in Type 2 Diabetic Mice.

ObjectivesIn this study, the effects of γ-aminobutyric acid (GABA)-rich sprouted adzuki beans on the glycolipid metabolism and gastrointestinal health were investigated in mice with type 2 diabetes mellitus (T2DM).MethodsMice with T2DM were subjected to dietary intervention with different doses of GABA-rich sprouted adzuki beans for 6 consecutive weeks, during which growth indicators, glycolipid metabolism, and the composition and diversity of the gut microbiota changes were observed.ResultsA high dietary intake of GABA-rich sprouted adzuki beans had a preventive effect against weight gain, significantly reduced serum levels of FBG, TG, and TC. Additionally, high dietary intake of GABA-rich sprouted adzuki beans increased the abundances of Firmicutes, Bacteroidetes, Verrucomicrobia, and Akkermansia, leading to a shift in the structure of the gut microbiota toward the dominance of probiotics with regulatory effects on glycolipid metabolism.ConclusionsGABA-rich sprouted adzuki beans can effectively control the bodyweight of mice with T2DM, maintain a balanced blood glucose level, improve glycolipid metabolism and the changes in the microbiota may mediate the anti-diabetic effect of sprouted adzuki beans.

Postharvest γ-aminobutyric acid application mitigates chilling injury of aonla (Emblica officinalis Gaertn.) fruit during low temperature storage

Aonla is a nutrients rich underutilized subtropical fruit. It has short shelf life and is prone to chilling injury (CI) below 6 °C. So, the effect of γ-aminobutyric acid [5 mmol L−1 (GABA)] was investigated on aonla fruit CI mitigation during low temperature storage at 5 ± 1 °C for 24 d. Results showed that GABA treatment markedly suppressed CI, decay incidence, membrane permeability, malondialdehyde, superoxide anion and hydrogen peroxide in contrast with control. Treated fruit showed higher activity of glutamate decarboxylase (GAD) and GABA transaminase (GABA-T) enzymes which ultimately resulted in increased endogenous GABA content accumulation. Similarly, GABA application stimulated the activities of Δ1-pyrroline-5-carboxylate synthetase (P5CS) and ornithine aminotransferase (OAT) enzymes which thus enhanced proline accumulation. The GABA treated fruit exhibited higher phenylalanine ammonia lyase (PAL) and reduced polyphenol oxidase (PPO) enzyme activity and showed higher total phenols accumulation. In addition, total flavonoids, ascorbic acid and glutathione content were also significantly higher in GABA treated aonla fruit. In addition, GABA treated aonla fruit exhibited markedly higher ascorbate peroxidase (APX) catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD) activities in comparison with the control. In addition, GABA treated fruit showed lower total soluble solids, ripening index and juice pH along with markedly higher concentration of titratable acidity. In conclusion, GABA treatment could be used for CI mitigation and overall quality maintenance of cold stored aonla fruit.

Biochemical changes and quality characterization of cold-stored ‘Sahebi’ grape in response to postharvest application of GABA

In this study, the effect of γ-aminobutyric acid (GABA) at 0 (control), 20 and 40 mM on maintaining postharvest quality, chilling tolerance and fungal decay of ‘Sahebi’ grapevine (Vitis vinifera L.) was investigated during 60 days storage at 1 °C. GABA-treated fruits especially at 40 mM showed less weight loss (35%), rachis browning (30%) and decay incident (63%) compared to the control. GABA-induced abscisic acid was linked to lower membrane electrolyte leakage (13%) in treated grapes. Moreover, at the end of 60 days, GABA treatment at 40 mM resulted in higher activities of antioxidant enzymes including superoxide dismutase (50%), catalase (35%), guaiacol peroxidase (65%), and ascorbate peroxidase (47%) and lower malondialdehyde (21%) compared to control samples. The highest soluble sugars and organic acids were related to 40 mM GABA-treated grape clusters. Phenolic compounds (phenolic acids, stilbenes, flavonoids and anthocyanidins) and antioxidant capacity increased in 40 mM GABA-treated grape due to lower polyphenol oxidase activity. Therefore, GABA is recommended for maintaining internal quality and reduction in fungal decay and chilling injury of grapes during postharvest storage.

Effect of γ-aminobutyric Acid on Phenolics Metabolism in Barley Seedlings under Low NaCl Treatment.

It has been revealed that high NaCl stress (>60 mmol L−1) induced phenolics accumulation in barley seedlings, with γ-aminobutyric acid (GABA) playing a key role. Interestingly, low NaCl stimulus (20 mmol L−1) enhancing phenolics synthesis and growth of barley seedlings was also reported recently. Hence, exogenous GABA and its bio-synthesis inhibitor 3-mercaptopropionic acid (3-MP) were applied to reveal the mechanism of GABA regulating phenolics metabolism in barley seedlings treated with 20 mmol L−1 NaCl. The contents of total phenolics and flavonoids significantly increased by 11.64% and 14.52% under NaCl, respectively. The addition of GABA further increased phenolics and flavonoids contents, especially for gallic acid, protocatechuic acid, caffeic acid, and quercetin, compared with NaCl treatment. Simultaneously, GABA increased the activities and mRNA levels of phenylalanine ammonia lyase (PAL), cinnamic acid 4-hydroxylase (C4H), and 4-coumalyl CoA ligase (4CL). The addition of 3-MP suppressed the above effects, except for increasing the protein levels of PAL, C4H, and 4CL. Low concentration of NaCl not only promoted growth, but also stimulated endogenous GABA metabolism to affect key enzymes activities and mRNA levels for phenolics synthesis in barley seedlings.

The Alteration of Chloride Homeostasis/GABAergic Signaling in Brain Disorders: Could Oxidative Stress Play a Role?

In neuronal precursors and immature neurons, the depolarizing (excitatory) effect of γ-Aminobutyric acid (GABA) signaling is associated with elevated [Cl−]i; as brain cells mature, a developmental switch occurs, leading to the decrease of [Cl−]i and to the hyperpolarizing (inhibitory) effect of GABAergic signaling. [Cl−]i is controlled by two chloride co-transporters: NKCC1, which causes Cl− to accumulate into the cells, and KCC2, which extrudes it. The ontogenetic upregulation of the latter determines the above-outlined switch; however, many other factors contribute to the correct [Cl−]i in mature neurons. The dysregulation of chloride homeostasis is involved in seizure generation and has been associated with schizophrenia, Down’s Syndrome, Autism Spectrum Disorder, and other neurodevelopmental disorders. Recently, much effort has been put into developing new drugs intended to inhibit NKCC1 activity, while no attention has been paid to the origin of [Cl−]i dysregulation. Our study examines the pathophysiology of Cl− homeostasis and focuses on the impact of oxidative stress (OS) and inflammation on the activity of Cl− co-transporters, highlighting the relevance of OS in numerous brain abnormalities and diseases. This hypothesis supports the importance of primary prevention during pregnancy. It also integrates the therapeutic framework addressed to restore normal GABAergic signaling by counteracting the alteration in chloride homeostasis in central nervous system (CNS) cells, aiming at limiting the use of drugs that potentially pose a health risk.

Gamma-aminobutyric acid facilitates the simultaneous production of biomass, astaxanthin and lipids in Haematococcus pluvialis under salinity and high-light stress conditions

The effects of γ-aminobutyric acid (GABA) on the biomass and astaxanthin and lipids production in Haematococcus pluvialis under combined salinity stress and high-light stresses were investigated. The results showed that the highest biomass (1.65 g L−1), astaxanthin production (3.86 mg L−1 d−1) and lipids content (55.11%) in H. pluvialis LUGU were observed under the 0.25 mM GABA treatment. Moreover, compared with salinity and high-light stress, GABA treatment also increased the transcript levels of biosynthesis genes, the contents of endogenous GABA and carbohydrates but decreased reactive oxygen species (ROS) levels. Further evidence revealed that intracellular GABA could regulate cell growth, astaxanthin production and lipids synthesis by mediating carotenogenesis, lipogenesis and ROS signalling. Collectively, this study provides a combined strategy for promoting the coproduction of astaxanthin and lipids and sheds light on the regulatory mechanism through which GABA affects cell growth, astaxanthin production and lipids biosynthesis in H. pluvialis under unfavourable conditions.

Effect of γ-Aminobutyric Acid (GABA) on the Metabolome of Two Strains of Lasiodiplodia theobromae Isolated from Grapevine.

The effect of γ-aminobutyric acid (GABA) on the metabolome of two strains of Lasiodiplodia theobromae isolated from grapevine that hold a different degree of virulence to the host plant (LA-SOL3 (more virulent), LA-SV1 (less virulent)) was investigated. The culture filtrates and crude extracts from the two strains grown in the presence and absence of 10 mM of GABA were tested for phytotoxicity on tomato plant cuttings and leaves, respectively. Considering the opportunistic nature of this fungus for humans, crude extracts were also tested for cytotoxicity on mammalian cell lines. We found that culture filtrates and crude extracts have a decreased toxicity in the presence of GABA. Metabolomic analysis, conducted on both strains at both growth conditions, revealed the production of several compounds, such as indole-3-carboxylic acid (ICA, which is the main compound produced by L. theobromae), 3-indolecarboxyaldehyde, (3R,4S)-botryodiplodin, (R)-mellein. Finally, data demonstrate that GABA both induces a decrease in the amount of ICA, and a diversification of the metabolites produced by L. theobromae.

Effects of dietary supplemented of γ-amino butyric acid on growth performance, blood biochemical indices and intestinal morphology of yellow-feathered broilers exposed to a high temperature environment

This experiment was conducted to study the effects of γ-amino butyric acid (GABA) on growth performance, blood biochemical indices and intestinal morphology of yellow-feathered broilers exposed to a high temperature environment. One hundred and forty four, 28-day-old male yellow-feathered broilers were separated into 2 groups with 6 replicates and 12 birds per replicate. The two experimental groups included: control group, which fed the basal diet, and GABA supplemented group, which fed the basal diet supplemented with 100 mg/kg GABA. After 7 days of feeding experimental diet at 26 °C, birds were fed the experimental diet and exposed to a high temperature environment at 35 °C and 60% RH for 14 days. Results revealed that average daily gain (ADG, p = .004) and average daily feed intake (ADFI, p = .003) of the GABA group were higher than control group, feed: gain ratio (F/G; p = .023) and mortality (p = .042) were lower than control group. The serum levels of glucose (GLU; p = .016), total cholesterol (T-CHO; p = .001), and low density lipoprotein (LDL; p = .001) as well as the activities of aspartate-aminotransferase (AST; p = .008), lactate dehydrogenase (LDH; p = .042) and creatine kinase (CK; p = .032) of the GABA group were lower than control group, while villus length (p = .016) of jejunum was higher than control group. In conclusion, adding 100 mg/kg GABA to diet can improve growth performance, reduce serum intracellular enzyme activities, protect the organs and intestinal morphology of yellow-feathered broilers exposed to a high temperature environment during 36-49 days of age. Highlights GABA improves growth performance of yellow-feathered broilers exposed to a high temperature environment. GABA protects the intestine of yellow-feathered broilers exposed to a high temperature environment.

Effect of γ-aminobutyric acid producing bacteria on in vitro rumen fermentation, growth performance, and meat quality of Hanwoo steers.

ObjectiveThe present study aimed to evaluate the effects of γ-aminobutyric acid (GABA)-producing bacteria (GPB) on in vitro rumen fermentation and on the growth performance and meat quality of Hanwoo steers.MethodsThe effects of GPB (Lactobacillus brevis YM 3-30)-produced and commercially available GABA were investigated using in vitro rumen fermentation. Using soybean meal as a substrate, either GPB-produced or commercially available GABA were added to the in vitro rumen fermentation bottles, as follows: control, no additive; T1, 2 g/L GPB; T2, 5 g/L GPB; T3, 2 g/L autoclaved GPB; T4, 5 g/L autoclaved GPB; T5, 2 g/L GABA; and T6, 5 g/L GABA. In addition, 27 Hanwoo steers (602.06±10.13 kg) were subjected to a 129-day feeding trial, during which they were fed daily with a commercially available total mixed ration that was supplemented with different amounts of GPB-produced GABA (control, no additive; T1, 2 g/L GPB; T2, 5 g/L GPB). The degree of marbling was assessed using the nine-point beef marbling standard while endotoxin was analyzed using a Chromo-Limulus amebocyte lysate test.ResultsIn regard to in vitro rumen fermentation, the addition of GPB-produced GABA failed to significantly affect pH or total gas production but did increase the ammonia nitrogen (NH3-N) concentration (p<0.05) and reduce total biogenic amines (p<0.05). Animals fed the GPB-produced GABA diet exhibited significantly lower levels of blood endotoxins than control animals and yielded comparable average daily gain, feed conversion ratio, and beef marbling scores.ConclusionThe addition of GPB improved in vitro fermentation by reducing biogenic amine production and by increasing both antioxidant activity and NH3-N production. Moreover, it also reduced the blood endotoxin levels of Hanwoo steers.

Effect of γ-aminobutyric acid on the antioxidant system and biochemical changes of mango fruit during storage

Postharvest management of mango, as a climacteric fruit with high perishability rate, is of particular economic importance. In this study, the effect of γ-aminobutyric acid (GABA) (50, 100 and 200 µmol L−1) were evaluated regarding efficacy of delaying in fruit softening and maintaining nutritional quality of mango fruit during storage at 15 ± 1 °C and 85% RH. According to the results, the total soluble solids content and titratable acidity were not influenced by the γ-aminobutyric acid significantly; while, at 200 µmol L−1 it has maintained firmness, ascorbic acid, phenols and flavonoids content of mango significantly. Also, the higher antioxidant capacity was found in treated fruits. The treated fruits had more activity of the catalase and peroxidase enzymes than the control. The γ-aminobutyric acid significantly controls the activity of polyphenol oxidase enzyme during storage. The GABA treated fruits showed the higher a* value and lower b* and L* during the storage. These findings suggested that γ-aminobutyric acid treatment could be useful at a proper concentration in order to improve postharvest quality of mango.

Effects of γ-aminobutyric acid and hydrochloric acid on growth performance, nutrient digestibility and fecal score of growing pigs

Effects of γ-aminobutyric acid and hydrochloric acid on growth performance, nutrient digestibility and fecal score of growing pigs

Effects of γ-aminobutyric Acid on Mortality in Laying Hens During Summer Time

Effects of γ-aminobutyric Acid on Mortality in Laying Hens During Summer Time

Effects of γ-aminobutyric acid on aggressive behaviour, jejunum villus morphology, serum biochemical indicators and hippocampal neuropeptide mRNA levels in piglets at weaning with mixing

The effects of γ-aminobutyric acid (GABA) on weanling piglets after mixing stress were investigated and the underlying molecular mechanism was analyzed. Sixty weaning piglets were randomly assigned to either the control group (weaning and mixing with a 3 : 3 sex ratio) or the GABA supplement group (30 mg GABA/kg body weight/day + weaning and mixing with a 3 : 3 sex ratio). Aggressive behaviours have been recorded for 2 days and the number of lesions for 3 days. The diarrhea rate on day 6 post-weaning and mixing was analyzed. Serum biochemical indicators, antioxidant variables, jejunum villus morphology and mRNA levels of stress-related neuropeptide genes of the hippocampus were investigated. The GABA addition decreased serum adrenocorticotropic hormone concentrations (P &amp;lt; 0.05), aggressive behaviours of weaned piglets 5 h after mixing (P &amp;lt; 0.05), lesion scores over the entire 3-day period (P &amp;lt; 0.01) and diarrhea rate (P &amp;lt; 0.01) and improved jejunum villus integrity. Serum neuropeptide Y (NPY) concentration (P &amp;lt; 0.05) and total superoxide dismutase activity (P &amp;lt; 0.01) were increased in the GABA supplement group, whereas serum malondialdehyde concentration had a decreasing tendency (0.05 &amp;lt; P &amp;lt; 0.1), and glutathione peroxidase activity had an increasing tendency (0.05 &amp;lt; P &amp;lt; 0.1). The GABA treatment group had increased mRNA levels of NPY (P &amp;lt; 0.05) and peptide YY (PYY) (P &amp;lt; 0.05) in the hippocampus, which may contribute to insights into the regulatory mechanism of GABA in weaning and mixing stress. The addition of GABA is beneficial to reduce weaning and mixing stress in piglets, and NPY and PYY may mediate the process.

Effects of γ-Aminobutyric Acid on the Erectogenic Properties of Sildenafil

Erectile dysfunction (ED) is a disorder of increasing socio-economic burden. Therapeutic drugs such as sildenafil have been in use for the treatment of ED, but with their associated side effects. γ-aminobutyric acid (GABA) is a neurotransmitter with possible vasodilatory properties. In this study, the effect of GABA on the erectogenic properties of sildenafil was investigated. Aqueous solution of GABA and sildenafil (1 mM) was separately prepared as well as the mixtures of both (75% GABA + 25% sildenafil; 50% GABA + 50% sildenafil; 25% GABA + 75% sildenafil). Thereafter, the in vitro effects of all the studied samples on the activities of arginase, angiotensin-I converting enzyme (ACE) and acetylcholinesterase (AChE) were investigated. The results revealed that all the samples inhibited arginase, ACE and AChE activities. Considering the various combinations, 25% GABA + 75% sildenafil had the highest arginase inhibitory effect, 50% GABA + 50% sildenafil showed the highest ACE inhibiting effect, while 25% GABA + 75% sildenafil exhibited the highest AChE inhibitory effect. Therefore, the observed enzyme inhibiting effect of sildenafil, GABA and their various combinations on rat penile arginase, ACE and AChE activities could be part of the mechanism by which they elicit their erectogenic properties. The various combinations could thus serve as therapeutic intervention for the management of ED with a possible reduction in the side effects associated with the use of sildenafil; nevertheless, the combination of 75% GABA with 25% sildenafil exhibited the highest erectogenic potential.