GABA administration improves liver function and insulin resistance in offspring of type 2 diabetic rats.

This study investigated the role of GABA in attenuating liver insulin resistance (IR) in type 2 diabetes parents and reducing its risk in their descendants' liver. Both sexes' rats were divided into four groups of non-diabetic control, diabetic control (DC), GABA-treated (GABA), and insulin-treated (Ins). The study duration lasted for six months and the young animals followed for four months. Consequently, hyperinsulinemic-euglycemic clamp was performed for all animals. Apart from insulin tolerance test (ITT), serum and liver lipid profile were measured in all groups. Glycogen levels, expression of Foxo1, Irs2, Akt2, and Pepck genes in the liver were assessed for all groups. Overall, GABA improved ITT, increased liver glycogen levels and decreased lipid profile, blood glucose level, and HbA1c in parents and their offspring in compared to the DC group. GIR also increased in both parents and their offspring by GABA. Moreover, the expression of Foxo1, Irs2, Akt2, and Pepck genes improved in GABA-treated parents and their descendants in compared to DC group. Results indicated that GABA reduced liver IR in both parents and their offspring via affecting their liver insulin signaling and gluconeogenesis pathways.

Regulation of secondary antioxidants and carbohydrates by gamma-aminobutyric acid under salinity-alkalinity stress in rice (Oryza sativa L.).

Gamma-aminobutyric acid (GABA) is known to improve tolerance against abiotic stresses but less studied for salinity-alkalinity stress (SAS). In the present study, GABA regulation of secondary antioxidants and carbohydrates was studied in rice in the presence and absence of SAS. About 1.5 mM GABA, 200 mM SAS, GABA + SAS were applied to 5-day old seedlings, and thereafter measurements were done in shoots and roots at 24, 48, 72 h in rice cultivars CSR 43 (tolerant) and Pusa 44 (susceptible). SAS was applied in molar ratio of 1:9:9:1 of NaCl:Na2SO4:NaHCO3:Na2CO3. Peroxidases (POX), polyphenol oxidases (PPO), lignin, flavonoids and phenolics from secondary metabolism and invertases, hexoses, sucrose and starch from carbohydrate metabolism were studied. Pusa 44 increased soluble POX, lignin, flavonoids in shoots but deficient in roots during stress period but improved under GABA + SAS. CSR 43 increased soluble POX, lignin, flavonoids in roots consistently throughout the stress period and also improved under GABA + SAS. Early increase in cell wall POX/PPO under SAS was seen in CSR 43 only, while Pusa 44 improved this under GABA + SAS. During stress period, CSR 43 showed an increasing trend of cell wall invertase activity, sucrose, sucrose-to-hexose ratio and starch in roots but Pusa 44 showed poor such response but Pusa 44 improved starch, sucrose, sucrose-to-hexose ratio by significant amount in both shoots and roots under GABA + SAS. The overall study indicated GABA as an important regulator of secondary and carbohydrate metabolisms. Besides improving secondary antioxidants, GABA under stress may improve cellular reserves like starch and protective sugars like sucrose.

Exosome-Mediated Activation of Neuronal Cells Triggered by γ-Aminobutyric Acid (GABA).

γ-Aminobutyric acid (GABA) is a potent bioactive amino acid, and several studies have shown that oral administration of GABA induces relaxation, improves sleep, and reduces psychological stress and fatigue. In a recent study, we reported that exosomes derived from GABA-treated intestinal cells serve as signal transducers that mediate brain-gut interactions. Therefore, the purpose of this study was to verify the functionality of GABA-derived exosomes and to examine the possibility of improving memory function following GABA administration. The results showed that exosomes derived from GABA-treated intestinal cells (Caco-2) activated neuronal cells (SH-SY5Y) by regulating genes related to neuronal cell functions. Furthermore, we found that exosomes derived from the serum of GABA-treated mice also activated SH-SY5Y cells, indicating that exosomes, which are capable of activating neuronal cells, circulate in the blood of mice orally administered GABA. Finally, we performed a microarray analysis of mRNA isolated from the hippocampus of mice that were orally administered GABA. The results revealed changes in the expression of genes related to brain function. Gene Set Enrichment Analysis (GSEA) showed that oral administration of GABA affected the expression of genes related to memory function in the hippocampus.

A double-blind, placebo-controlled, randomised-designed GABA tea study in children diagnosed with autism spectrum conditions: a feasibility study clinical trial registration: ISRCTN 72571312.

Objective: The research has shown an association with sensorimotor integration and symptomology of Autism Spectrum Conditions (ASC). Specific areas of the brain that are involved in sensorimotor integration, such as the cerebellum and basal ganglia, are pathologically different in individuals with ASC in comparison to typically developing (TD) peers. These brain regions contain GABAergic inhibitory neurons that release an inhibitory neurotransmitter, γ-Aminobutyric acid (GABA). Brain GABA levels are decreased in ASC. This study explored the effect of introducing a non-invasive GABA substitute, in the form of GABA Oolong tea, on sensorimotor skills, ASC profiles, anxieties and sleep of children with ASC. Methods: Nine children took part: (5 male, 4 female). Each child participated in three tea conditions: high GABA, high L-Theanine (a compound that increases GABA), placebo with low GABA. A double-blind, repeated measures design was employed. Measures were taken after each tea condition. Sensory and ASC profiles were scored using parental questionnaires. Motor skills were assessed using a gold standard coordination assessment. Sleep was monitored using an actiwatch and anxiety measured through cortisol assays. Subjective views were sought from parents on 'best' tea. Results: The results showed significant improvement in manual dexterity and some large individual improvements in balance, sensory responsivity, DSM-5 criteria and cortisol levels with GABA tea. Improvements were also seen in the L-Theanine condition although they were more sporadic. Conclusions: These results suggest that sensorimotor abilities, anxiety levels and DSM-5 symptomology of children with ASC can benefit from the administration of GABA in the form of Oolong tea.

GABA-enriched teas as neuro-nutraceuticals.

Teas enriched in GABA are consumed for their beneficial effects on blood pressure, stress and anxiety. These effects may involve actions of GABA on the central and peripheral nervous systems. The anaerobic procedures for the production of GABA-enriched teas increase GABA levels by 10-20 times. They also significantly alter the levels of other constituents that may interact with the actions of GABA. These include epigallocatechin gallate, caffeine and theanine. The possible interactions of these active constituents make the understanding of the effects of GABA-enriched teas complex. More data is needed to establish where and how GABA is acting following consumption of GABA-enriched teas. While there is considerable evidence that such GABA is acting on GABA receptors in the periphery, there is rather less evidence that is acting directly in the brain. Certainly, there is more to the action of GABA-enriched teas than GABA itself.

Effects of dietary gamma-aminobutyric acid supplementation on amino acid profile, intestinal immunity, and microbiota in ETEC-challenged piglets.

Enterotoxigenic Escherichia coli (ETEC) infection is the most common cause of diarrhea in piglets, and ETEC could increase intestinal gamma-aminobutyric acid (GABA)-producing bacteria to affect intestinal immunity. However, the effect of GABA on ETEC-infected piglets is still unclear. This study aims at investigating the impact of dietary GABA supplementation on the growth performance, diarrhea, intestinal morphology, serum amino acid profile, intestinal immunity, and microbiota  in the ETEC-infected piglet model. Eighteen piglets were randomly divided into two groups, in which the piglets were fed with a basal diet with 20 mg kg-1 GABA supplementation or not. The experiment lasted for three weeks, and the piglets were challenged with ETEC K88 on the fifteenth day. The results showed that dietary GABA reduced the feed conversion ratio, promoted the kidney organ index but did not affect the diarrheal score and small intestinal morphology in ETEC-challenged piglets. Ileal mucosal amino acids (such as carnosine and anserine) and serum amino acids (including threonine and GABA) were increased upon GABA supplementation. GABA enhanced ileal gene expression of TNF-α, IFN-γ, pIgR, and MUC2, while inhibited the ileal expression of IL-18 in ETEC-challenged piglets. GABA supplementation also highly regulated the intestinal microbiota by promoting community richness and diversity and reducing the abundance of the dominant microbial population of the ileal microbiota. Collectively, GABA improves growth performance, regulates the serum amino acid profile, intestinal immunity, and gut microbiota in ETEC-challenged piglets. This study is a fine attempt to reveal the function of GABA in ETEC-infected piglets. It would contribute to the understanding of the roles of exogenous nutrition on the host response to ETEC infection.

Differential effects of GABAA receptor activation in the prelimbic and orbitofrontal cortices on anxiety.

RATIONALE: The development of effective anxiety treatments has been hindered by limited understanding of the neurobiological mechanisms involved in anxiety regulation. Whilst gamma-aminobutyric acid (GABA) neurotransmission in the prefrontal cortex (PFC) is one mechanism consistently implicated in anxiety regulation, PFC subregions may contribute uniquely. OBJECTIVES: The present study examined the effects of inactivating the PFC subregions of the prelimbic cortex (PrL) or orbitofrontal cortex (OFC) through GABAA receptor (GABAAR) activation, on anxiety behaviours in male Wistar rats. METHODS: Sixty-six male Wistar rats were surgically implanted with bilateral cannulae into the PrL (n = 33) or the OFC (n = 33). Rats then received a microinjection of either the GABAA receptor agonist muscimol or vehicle prior to each experiment, conducted 1 week apart. Measures of anxiety were examined using the elevated plus maze (EPM) and the emergence test (ET). The effect on locomotor activity (baseline or methamphetamine-induced) was also tested. RESULTS: Differential effects of brain region inactivation on anxiety-like behaviour were shown by measures in the EPM and ET; muscimol infused into the PrL-reduced anxiety-like behaviour, yet had no significant effect when infused into the OFC, compared with control treated rats. No effects on locomotor activity at baseline or following methamphetamine treatment were found. CONCLUSIONS: This study highlights that activation of GABAARs specifically within the PrL, but not OFC, reduces anxiety behaviours in male rats. This suggests that activity of the PrL plays a more important role than the OFC in the neurobiological mechanisms of unconditioned anxiety and should be targeted for future therapies.

The anti-heat stress effects of Chinese herbal medicine prescriptions and rumen-protected γ-aminobutyric acid on growth performance, apparent nutrient digestibility, and health status in beef cattle.

This study aims to evaluate the anti-heat stress effect of Chinese herbal medicine (CHM) prescription, rumen-protected γ-aminobutyric acid (RP-GABA), and CHM plus RP-GABA co-medication on growth performance, apparent digestibility, and serum parameters in heat-stressed beef cattle. Forty beef cattle were randomly divided into four groups. Control group was supplied with basal diet, while CHM, γ-aminobutyric acid (GABA), and CHM + GABA groups were, respectively, supplied with CHM, RP-GABA, and CHM plus RP-GABA in basal diet. Our result indicated that CHM + GABA elevated apparent digestibility including crude protein, Ca, P, crude fat (CF) (p < .01), and neutral detergent fiber (NDF) (p < .05), but no difference was found with CF and NDF digestibility both in CHM and GABA group (p > .05). More importantly, average daily gain (ADG) was improved in CHM, GABA, and CHM + GABA groups, while average daily feed intake (ADFI) significantly increased only in CHM + GABA groups (p < .05). Meanwhile, CHM + GABA displayed notably more positive effect in serum hormones, immune globulin, ions contents, and blood inflammatory cytokines than other treatment groups and control group. These results demonstrated that both CHM and GABA are effective in alleviating heat stress response and the co-medication has a synergistic effect on anti-heat stress.

GABA consumption during early pregnancy impairs endometrial receptivity and embryo development in mice.

γ-Aminobutyrate (GABA) is commonly used as a food supplement and a health care product by young females, due to its positive roles in relieving stress, alleviating anxiety, and improving sleep. However, its recommended daily dose in different products varies widely. Besides, it is unknown whether, and how, GABA consumption during early pregnancy influences pregnancy establishment. In this study, we found that when pregnant mice were treated with a high (12.5 mg/g) dose of GABA (orally) during preimplantation, there was a reduction in the number of implantation sites on day 5 of pregnancy. Also, among these unimplanted embryos, most exhibited morphological degeneration and developmental retardation, and only a few of them developed into blastocysts but could not implant into the uterus. Moreover, the expression of uterine receptivity-related factors-LIF, E-cadherin, and HOXA10-were all downregulated, while the number of uterine glands was reduced in the high GABA dose group. Finally, in vitro results demonstrated that GABA (ranging from 10 to 50 µg/µL) markedly inhibited preimplantation embryo development in a dose-response manner. However, this inhibitory effect was not observed when the embryos were pretreated with 40 µΜ 2-hydroxysaclofen, a GABAB antagonist, indicating that GABA exerts its inhibitory effects via its B-type receptor. Our results suggest that exposure to certain GABA concentrations, during early pregnancy, can impair preimplantation embryo development via its B-type receptor, and endometrial receptivity, which greatly disturbs early embryo implantation in mice. These findings could raise concerns about GABA consumption during the early stages of pregnancy.

Steady-state activation and modulation of the synaptic-type α1ß2γ2L GABAA receptor by combinations of physiological and clinical ligands.

The synaptic α1ß2γ2 GABAA receptor is activated phasically by presynaptically released GABA. The receptor is considered to be inactive between synaptic events when exposed to ambient GABA because of its low resting affinity to the transmitter. We tested the hypothesis that a combination of physiological and/or clinical positive allosteric modulators of the GABAA receptor with ambient GABA generates measurable steady-state activity. Recombinant α1ß2γ2L GABAA receptors were expressed in Xenopus oocytes and activated by combinations of low concentrations of orthosteric (GABA, taurine) and allosteric (the steroid allopregnanolone, the anesthetic propofol) agonists, in the absence and presence of the inhibitory steroid pregnenolone sulfate. Steady-state activity was analyzed using the three-state cyclic Resting-Active-Desensitized model. We estimate that the steady-state open probability of the synaptic α1ß2γ2L GABAA receptor in the presence of ambient GABA (1 µmol/L), taurine (10 µmol/L), and physiological levels of allopregnanolone (0.01 µmol/L) and pregnenolone sulfate (0.1 µmol/L) is 0.008. Coapplication of a clinical concentration of propofol (1 µmol/L) increases the steady-state open probability to 0.03. Comparison of total charge transfer for phasic and tonic activity indicates that steady-state activity can contribute strongly (~20 to >99%) to integrated activity from the synaptic GABAA receptor.

Nucleus Accumbens Fast-Spiking Interneurons Constrain Impulsive Action.

BACKGROUND: The nucleus accumbens (NAc) controls multiple facets of impulsivity but is a heterogeneous brain region with diverse microcircuitry. Prior literature links impulsive behavior in rodents to gamma-aminobutyric acid signaling in the NAc. Here, we studied the regulation of impulsive behavior by fast-spiking interneurons (FSIs), a strong source of gamma-aminobutyric acid-mediated synaptic inhibition in the NAc. METHODS: Male and female transgenic mice expressing Cre recombinase in FSIs allowed us to identify these sparsely distributed cells in the NAc. We used a 5-choice serial reaction time task to measure both impulsive action and sustained attention. During the 5-choice serial reaction time task, we monitored FSI activity with fiber photometry calcium imaging and manipulated FSI activity with chemogenetic and optogenetic methodology. We used electrophysiology, optogenetics, and fluorescent in situ hybridization to confirm these methods were robust and specific to FSIs. RESULTS: In mice performing the 5-choice serial reaction time task, NAc FSIs showed sustained activity on trials ending with correct responses, but FSI activity declined over time on trials ending with premature responses. The number of premature responses increased significantly after sustained chemogenetic inhibition or temporally delimited optogenetic inhibition of NAc FSIs, without any changes in response latencies or general locomotor activity. CONCLUSIONS: These experiments provide strong evidence that NAc FSIs constrain impulsive actions, most likely through gamma-aminobutyric acid-mediated synaptic inhibition of medium spiny projection neurons. Our findings may provide insight into the pathophysiology of disorders associated with impulsivity and may inform the development of circuit-based therapeutic interventions.

Early Treatment with Empagliflozin and GABA Improves ß-Cell Mass and Glucose Tolerance in Streptozotocin-Treated Mice.

While the autoimmune character of T1D (type 1 diabetes) is being challenged, it is currently recognized that inflammation plays a key role in its development. We hypothesized that glucotoxicity could contribute to ß-cell mass destruction through participation in islet inflammation. We evaluated the potential of empagliflozin (EMPA) and GABA (gamma-aminobutyric acid) to protect ß-cell mass against glucotoxicity and to increase ß-cell mass after diagnosis of T1D. Empagliflozin is a SGLT2 (sodium-dependent glucose cotransporter) inhibitor which thereby blocks glucose recapture by the kidney and promotes glucose excretion in urine. GABA is an inhibitory neurotransmitter, which stimulates α-to-ß cell transdifferentiation. In streptozotocin-treated mice, empagliflozin and/or GABA were delivered for a period of five days or three weeks. As compared to untreated T1D mice, EMPA-treated T1D mice had decreased FFA (free fatty acid) levels and improved glucose homeostasis. EMPA-treated T1D mice had higher islet density, with preserved architecture, compared to T1D mice, and EMPA-treated T1D mice also differed from T1D mice by the total absence of immune cell infiltration within islets. Islets from EMPA-treated mice were also less subjected to ER (endoplasmic reticulum) stress and inflammation, as shown by qPCR analysis. Glucose homeostasis parameters and islet area/pancreas area ratio improved, as compared to diabetic controls, when T1D mice were treated for three weeks with GABA and EMPA. T1D EMPA+GABA mice had higher glucagon levels than T1D mice, without modifications of glucagon area/islet area ratios. In conclusion, empagliflozin and GABA, used in monotherapy in streptozotocin-induced diabetic mice, have positive effects on ß-cell mass preservation or proliferation through an indirect effect on islet cell inflammation and ER stress. Further research is mandatory to evaluate whether empagliflozin and GABA may be a potential therapeutic target for the protection of ß-cell mass after new-onset T1D.

Bioactive nanoparticle embedded microcapsules for improving the efficacy of type I diabetes therapy.

In order to overcome the side effects of pancreatic transplantation and insulin injection treatment for type I diabetes, we established a drug delivery system employing nanoparticle embedded microcapsules (NEMs). The system co-encapsulated chitosan nanoparticles with γ-aminobutyric acid and ß-TC-6 cells for combined drug and cell therapy in diabetes mellitus (DM). The NEMs, which were formed via high-voltage electrostatic method, had an excellent sphericity with a smooth surface. The average size NEM was 245.52 ± 22.00 µm, which indicated a good size for cell encapsulation. Haemolysis rate of NEMs at concentrations of 100, 200 or 300 mg/mL were all below 5%. Relative viability rates of L929 cells with the same concentrations at 24, 48 or 72 h were all above 80%. We implanted bioactive NEMs into type 1 DM mice to evaluate the effect of the combined therapy. The level of blood glucose in the group receiving the combined therapy decreased during the first 2 weeks of treatment. During the next week, the level of blood glucose stayed in a safe range. Body weight continuously increased during the postoperative period after combined therapy group. Oral glucose tolerance test (OGTT) performed after 24 d showed that the level of blood glucose combined therapy reached the maximum peak of 13.04 mmol/L, lower than 16.56 mmol/L for the cell therapy group. This primary study indicated that microencapsulation technology and combined therapy are promising for the treatment of type I diabetes mellitus.

The pro-algesic effect of γ-aminobutyric acid (GABA) injection into the masseter muscle of healthy men and women.

Background and aims Preclinical studies have reported that activation of peripheral γ-aminobutyric acid A (GABAA) receptors may result in analgesia. The current study was conducted in young healthy men (n = 30) and women (n = 28) to determine whether injections of GABA into the masseter muscle reduce pain in a sex-related manner. Methods The effect of injection of GABA alone, or in combination with the non-inflammatory algogen glutamate, was assessed in two separate studies. Lorazepam, a positive allosteric modulator of the GABAA-receptor, was co-injected with GABA in both studies to explore the role of this receptor in muscle pain responses of healthy human volunteers. Masticatory muscle mechanical pain intensity was recorded on an electronic visual analogue scale (VAS) while muscle pain sensitivity was assessed by determining the pressure pain threshold (PPT), tolerance and maximal jaw opening (MJO) of the subjects prior to, and again after the various intramuscular injections. Results Intramuscular injection of GABA alone was reported to be significantly more painful, in a concentration related manner, than saline control injections, and this pain was further increased by co-injection of lorazepam with GABA. Co-injection of GABA with glutamate was found to significantly increase glutamate-evoked masseter muscle pain in men, but not in women. There was no effect of injections of either GABA alone, or GABA with glutamate, on PPT, tolerance or maximum jaw opening. Conclusions Injection of GABA into the human masseter muscle appears to excite nociceptors to produce muscle pain without a longer term effect on mechanical pain sensitivity in the muscle. The findings suggest that GABA-mediated pain in humans is produced through peripheral GABAA receptor activation. The mechanism underlying the sex-related difference in the effect of GABA on glutamate-evoked muscle pain was speculated to be due to a methodological artifact. Implications This study was designed to detect analgesic rather than algesic effects of peripherally administered GABA, and as a result, the concentration of glutamate chosen for injection was close to the maximal pain response for healthy women, based on previously determined pain-concentration response relationships for glutamate. This may explain the finding of greater pain in men than women, when GABA and glutamate were co-injected. Overall, the findings suggest that activation of peripheral GABAA receptors in human masticatory muscle produces pain, possibly due to depolarization of the masticatory muscle afferent fibers.

Effect of gamma aminobutyric acid (GABA) or GABA with glutamic acid decarboxylase (GAD) on the progression of type 1 diabetes mellitus in children: Trial design and methodology.

BACKGROUND: Evidence suggests that GABA may reduce pancreatic inflammation, protect ß-cells from autoimmune destruction, and potentiate the regeneration of new ß-cells in the setting of type 1 diabetes mellitus (T1DM). The enzyme GAD, also expressed in human pancreatic ß-cells, is an antigenic target of reactive T cells. We hypothesized that treatment of children with recent onset T1DM with GABA or combination GABA with GAD will preserve ß-cell function and ameliorate autoimmune dysregulation. METHODS: This is a one-year, prospective, randomized, double-blind, placebo-controlled trial. Ninety-nine patients aged 4-18 years with newly diagnosed T1DM are randomized into three treatment groups: 1) oral GABA twice daily in addition to two injections of recombinant GAD enzyme, 2) oral GABA plus placebo GAD injections, or 3) placebo GABA and placebo GAD. Patients are evaluated at baseline and months 1, 5, 8 and 12. Mixed meal tolerance testing is performed at all but the 8-month visit. Laboratory studies will assess indices of beta and alpha cell function, glycemic control, immunophenotyping, and diabetes-related autoantibodies. RESULTS: The primary outcome is the effect on pancreatic ß-cell function as measured by meal-stimulated c-peptide secretion compared between the treatment groups before and after one year of treatment. Secondary outcomes include: 1) fasting and meal stimulated glucagon and proinsulin levels, 2) response in insulin usage by participants, 3) indices of immune cell function, and 4) effect on autoantibodies GAD65, ICA512, and ZnT8. CONCLUSIONS: This trial will determine the safety and efficacy of GABA and combination GABA/GAD therapy to delay T1DM progression in children.

Electrophoretic Delivery of γ-aminobutyric Acid (GABA) into Epileptic Focus Prevents Seizures in Mice.

Epilepsy is a group of neurological disorders which affects millions of people worldwide. Although treatment with medication is helpful in 70% of the cases, serious side effects affect the quality of life of patients. Moreover, a high percentage of epileptic patients are drug resistant; in their case, neurosurgery or neurostimulation are necessary. Therefore, the major goal of epilepsy research is to discover new therapies which are either capable of curing epilepsy without side effects or preventing recurrent seizures in drug-resistant patients. Neuroengineering provides new approaches by using novel strategies and technologies to find better solutions to cure epileptic patients at risk. As a demonstration of a novel experimental protocol in an acute mouse model of epilepsy, a direct in situ electrophoretic drug delivery system is used. Namely, a neural probe incorporating a microfluidic ion pump (µFIP) for on-demand drug delivery and simultaneous recording of local neural activity is implanted and demonstrated to be capable of controlling 4-aminopyridine-induced (4AP-induced) seizure-like event (SLE) activity. The γ-aminobutyric acid (GABA) concentration is kept in the physiological range by the precise control of GABA delivery to reach an antiepileptic effect in the seizure focus but not to cause overinhibition-induced rebound bursts. The method allows both the detection of pathological activity and intervention to stop seizures by delivering inhibitory neurotransmitters directly to the epileptic focus with precise spatiotemporal control. As a result of the developments to the experimental method, SLEs can be induced in a highly localized manner that allows seizure control by the precisely tuned GABA delivery at the seizure onset.

A Randomized Clinical Efficacy Trial of Red Yeast Rice (Monascus pilosus) Against Hyperlipidemia.

Red yeast rice (RYR) has been used as an alternative treatment for hyperlipidemia. According to the previous studies, other compounds, besides monacolin K in RYR, may also reduce the serum lipid level. This study aims at examining the efficacy of monacolin K-rich and Gamma-Aminobutyric Acid (GABA)-rich RYR (Monascus pilosus) with regards to treating hyperlipidemia in a randomized control, double-blind clinical trial. In the research, we assigned 50 eligible subjects to monacolin K-rich RYR, GABA-rich RYR and placebo groups ( n=16 , 17, 17, respectively). The concentrations of TC, LDL-C, HDL, TG and blood biochemical data were evaluated at different phases: before applying (visit 1), after 1-month (visit 2), 2-month (visit 3), 3-month (visit 4) of providing the intervention and 1-month after ending the test food (visit 5) among three groups. During the 3-month intervention, the serum TC and LDL-C levels decreased significantly in the monacolin K group compared to the baseline and the other two groups. The Serum TG level declined steadily but was not statistically significant. Meanwhile, no marked differences in the serum HDL level were revealed among the three groups. Most safety assessment data had minor variation except two subjects (in monacolin K and GABA group separately) reported elevated liver enzymes. Monacolin K-rich RYR can reduce cholesterol as expected, while the GABA-rich RYR performed non-significant reduction on serum triglyceride. The research results demonstrate that using different concentrations and ratios between monacolin K and GABA could be beneficial for antihyperlipidemia.

Intervention mechanism of repeated oral GABA administration on anxiety-like behaviors induced by emotional stress in rats.

The purpose of this study was to investigate the effects and mechanism of repeated oral administration of gamma-aminobutyric acid (GABA) on anxiety-like behaviors induced by emotional stress. Male Sprague-Dawley rats were randomly divided into five groups (8 rats each): control, emotional stress model, three emotional stress + GABA-treated groups (0.5, 1, 2 mg/kg). The rats were given empty water bottles after the training of drinking water to induce emotional stress. Each group was treated with saline or different doses of GABA respectively for 21 consecutive days. Then open field and elevated plus maze were used to assess anxiety-like behaviors. Both frontal cortex and plasma NO metabolites nitrate and nitrite (NOx) levels were determined spectrophotometrically. Results showed that oral administration of GABA significantly reversed the stress-induced anxiety-like negative responses dose-dependently. The frontal cortex NOx levels were lower in stressed rats than in control group (P < 0.05), but higher in 2 mg/kg GABA-treated group than stress model group (P < 0.05). On the other hand, NOx levels in plasma showed a gradual decline trend. Collectively, these results suggest that short repeated oral administration of GABA has an anxiolytic-like effect possibly via preventing NO reduction caused by stress and improving availability of NO in the frontal cortex.