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35 pages, 2638 KiB  
Review
Genetic Divergence and Functional Significance of Bioactive Compounds in Rice and Barley: Implications for Biofortification and Human Health
by Essam ElShamey, Jiazhen Yang, Xiaomeng Yang, Md. Mahmudul Hasan, Tao Yang and Yawen Zeng
Int. J. Mol. Sci. 2025, 26(15), 7374; https://doi.org/10.3390/ijms26157374 - 30 Jul 2025
Viewed by 148
Abstract
The functional components in cereals (rice and barley), such as gamma-aminobutyric acid (GABA), resistant starch (RS), and alkaloids, play crucial roles in human health, offering benefits such as improved cardiovascular function, enhanced gut microbiota, and potential anticancer properties. Rice (Oryza sativa) [...] Read more.
The functional components in cereals (rice and barley), such as gamma-aminobutyric acid (GABA), resistant starch (RS), and alkaloids, play crucial roles in human health, offering benefits such as improved cardiovascular function, enhanced gut microbiota, and potential anticancer properties. Rice (Oryza sativa) and barley (Hordeum vulgare) are key dietary staples with distinct genetic architectures influencing the biosynthesis and accumulation of these bioactive compounds. In this study, we explore the interaction and divergence of gene loci associated with GABA, RS, and alkaloid pathways in rice and barley, leveraging comparative genomics to identify conserved and species-specific regulatory mechanisms. We highlight key quantitative trait loci (QTLs) and candidate genes, such as GAD (glutamate decarboxylase) for GABA synthesis, SSIIa and GBSS for RS formation, and alkaloid biosynthesis genes including CYP80G2. Additionally, we discuss the health implications of these functional components, including their roles in reducing hypertension, managing diabetes, and exhibiting neuroprotective effects. Understanding the genetic differences between rice and barley in accumulating these compounds can guide biofortification strategies to enhance nutritional quality in cereal crops, ultimately benefiting human health and dietary outcomes. Full article
(This article belongs to the Special Issue Molecular Insight into Plant Bioactive Compounds)
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23 pages, 2027 KiB  
Article
Effect of Maternal Dietary DHA and Prenatal Stress Mouse Model on Autistic-like Behaviors, Lipid Peroxidation Activity, and GABA Expression in Offspring Pups
by Taeseon Woo, Nick I. Ahmed, Michael K. Appenteng, Candice King, Runting Li, Kevin L. Fritsche, Grace Y. Sun, Jiankun Cui, Matthew J. Will, Sara V. Maurer, Hanna E. Stevens, David Q. Beversdorf and C. Michael Greenlief
Int. J. Mol. Sci. 2025, 26(14), 6730; https://doi.org/10.3390/ijms26146730 - 14 Jul 2025
Viewed by 303
Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restricted social communication and repetitive behaviors. Prenatal stress is critical in neurodevelopment and increases risk for ASD, particularly in those with greater genetic susceptibility to stress. Docosahexaenoic acid (DHA) is one of the [...] Read more.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restricted social communication and repetitive behaviors. Prenatal stress is critical in neurodevelopment and increases risk for ASD, particularly in those with greater genetic susceptibility to stress. Docosahexaenoic acid (DHA) is one of the most abundant ω-3 fatty acids in the membrane phospholipids of the mammalian brain, and dietary DHA plays an important role in brain development and maintenance of brain structure. In this study, we investigated whether peri-natal supplementation of DHA can alleviate autistic-like behaviors in a genetic risk/stress mouse model and how it alters lipid peroxidation activity and GABAergic system gene expression in the forebrain. Pregnant heterozygous serotonin transporter knockout (SERT-KO) and wild-type (WT) dams were placed in either non-stressed control conditions or chronic variable stress (CVS) conditions and fed either a control diet or a DHA-rich (1% by weight) diet. Offspring of each group were assessed for anxiety and autism-associated behavior at post-natal day 60 using an open field test, elevated plus maze test, repetitive behavior, and the 3-chamber social approach test. A liquid chromatography-mass spectrometry (LC-MS)-based method was used to follow changes in levels of lipid peroxidation products in the cerebral cortex. Male offspring of prenatally stressed SERT-het KO dams exhibited decreased social preference behaviors and increased repetitive grooming behaviors compared to WT control offspring. Moreover, DHA supplementation in male SERT-het mice decreased frequency of grooming behaviors albeit showing no associated effects on social behaviors. Regardless of stress conditions, supplementation of DHA to the WT mice did not result in alterations in grooming nor social interaction in the offspring. Furthermore, no apparent changes were observed in the lipid peroxidation products comparing the stressed and non-stressed brains. Gad2 was downregulated in the cortex of female offspring of prenatally stressed SERT-KO dams, and this change appeared to be rescued by DHA supplementation in offspring. Gad2 was upregulated in the striatum of male offspring of prenatally stressed SERT-KO dams, but DHA did not significantly alter the expression compared to the control diet condition. Full article
(This article belongs to the Collection Feature Papers in Bioactives and Nutraceuticals)
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17 pages, 847 KiB  
Review
Mechanistic Links Between Gut Dysbiosis, Insulin Resistance, and Autism Spectrum Disorder
by Patricia Guevara-Ramírez, Rafael Tamayo-Trujillo, Viviana A. Ruiz-Pozo, Santiago Cadena-Ullauri, Elius Paz-Cruz and Ana Karina Zambrano
Int. J. Mol. Sci. 2025, 26(13), 6537; https://doi.org/10.3390/ijms26136537 - 7 Jul 2025
Viewed by 949
Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental condition frequently associated with gastrointestinal symptoms, gut dysbiosis, and metabolic dysfunctions such as insulin resistance (IR). Recent evidence suggests that the gut microbiota may influence both metabolic and neurological processes through the gut–brain–metabolic axis. This review [...] Read more.
Autism spectrum disorder (ASD) is a neurodevelopmental condition frequently associated with gastrointestinal symptoms, gut dysbiosis, and metabolic dysfunctions such as insulin resistance (IR). Recent evidence suggests that the gut microbiota may influence both metabolic and neurological processes through the gut–brain–metabolic axis. This review explores the molecular mechanisms linking dysbiosis, IR, and ASD, focusing on pathways such as TLR/NF-κB activation, PI3K/Akt/mTOR disruption, and the action of microbial metabolites, like short-chain fatty acids (SCFAs), lipopolysaccharide (LPS), and γ-aminobutyric acid (GABA). We discuss how dysbiosis may contribute to increased intestinal permeability, systemic inflammation, and neuroimmune activation, ultimately affecting brain development and behavior. Common microbial alterations in ASD and IR—including increased Clostridium, Desulfovibrio, and Alistipes, and reduced Bifidobacterium and butyrate-producing genera—suggest a shared pathophysiology. We also highlight potential therapeutic strategies, such as microbiota modulation, insulin-like growth factor 1 (IGF-1) treatment, and dietary interventions. Understanding these interconnected mechanisms may support the development of microbiota-targeted approaches for individuals with ASD metabolic comorbidities. Full article
(This article belongs to the Special Issue The Molecular and Cellular Aspects of Insulin Resistance)
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19 pages, 591 KiB  
Article
Development of a Guava Jelly Drink with Potential Antioxidant, Anti-Inflammation, Neurotransmitter, and Gut Microbiota Benefits
by Hai-Ha Nguyen, Jintanaporn Wattanathorn, Wipawee Thukham-Mee, Supaporn Muchimapura and Pongsatorn Paholpak
Foods 2025, 14(13), 2401; https://doi.org/10.3390/foods14132401 - 7 Jul 2025
Viewed by 429
Abstract
Due to the roles of oxidative stress, inflammation, and neurotransmitter imbalances in cognitive and mental dysfunction, we aimed to develop a functional drink with antioxidant and anti-inflammatory properties as well as the potential to support neurotransmitter balance for improved cognition and mental health. [...] Read more.
Due to the roles of oxidative stress, inflammation, and neurotransmitter imbalances in cognitive and mental dysfunction, we aimed to develop a functional drink with antioxidant and anti-inflammatory properties as well as the potential to support neurotransmitter balance for improved cognition and mental health. The Teng Mo, Fen Hong Mee, and Hong Chon Su guava varieties were screened for their polyphenol and flavonoid contents, antioxidant and anti-inflammatory effects, and suppressive effects on acetylcholinesterase (AChE), monoamine oxidase (MAO), GABA transaminase (GABA-T), and glutamate decarboxylase (GAD). Juice from the cultivar with the highest potential was selected and mixed with mint and honey syrups, pomelo-derived dietary fiber, ascorbic acid, agar, water, and fruit puree (pear/apple/orange) to create three guava jelly drink formulations. The formulation with pear puree showed the highest biological potential and was selected as the final product. It is rich in vitamin C, gallic acid, and dietary fiber, and provides approximately 37 Kcal/100 g. It also promotes the growth of lactic acid-producing bacteria in the culture. Thus, our drink shows the potential to reduce oxidative stress and inflammation, improve neurotransmitter regulation, and stimulate the gut–brain axis, thereby promoting cognition and mental wellness. However, clinical research is essential to confirm these potential benefits. Full article
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14 pages, 998 KiB  
Article
The Paradox of Clean Eating: Neuroactive Dysbiosis and Pesticide Residues in Fruit- and Vegetable-Based Diets
by Ramona Alina Tomuța, Andrada Florina Moldovan, Loredana Matiș, Lavinia Maris, Timea Claudia Ghitea and Florin Banica
Toxics 2025, 13(6), 504; https://doi.org/10.3390/toxics13060504 - 15 Jun 2025
Viewed by 528
Abstract
(1) Background: Exposure to pesticide residues through food remains a critical issue in public health, especially given their potential cumulative neurotoxic effects. (2) Methods: This study investigated the presence of pesticide residues in commonly consumed vegetables, fruits, and cereals based on official laboratory [...] Read more.
(1) Background: Exposure to pesticide residues through food remains a critical issue in public health, especially given their potential cumulative neurotoxic effects. (2) Methods: This study investigated the presence of pesticide residues in commonly consumed vegetables, fruits, and cereals based on official laboratory reports and evaluated the intestinal microbiome profiles of individuals whose diets consisted of over 50% plant-based foods. (3) Results: Analytical results from accredited laboratories in Romania demonstrated that all tested food samples were compliant with European regulations (Regulation (EC) 396/2005), with either undetectable or below-quantification-limit pesticide residues. However, organophosphates such as chlorpyrifos and diazinon were frequently tested, indicating persistent regulatory concern due to their known neurotoxic potential. A parallel analysis of stool samples revealed significant imbalances in neuroactive gut bacteria, including consistently low levels of Bifidobacterium and Lactobacillus species, and elevated levels of Oscillibacter and Alistipes, which are implicated in modulating GABA and serotonin pathways. Markers of proinflammatory activity, such as LPS-positive bacteria and histamine producers, were also elevated. (4) Conclusions: These findings suggest that even in diets rich in plant-based foods, microbial dysbiosis with neuroactive relevance can occur, potentially linked to environmental or dietary factors. The study underscores the need for a comprehensive evaluation of food safety and microbiome function as interconnected determinants of neurological health. Full article
(This article belongs to the Section Neurotoxicity)
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21 pages, 498 KiB  
Review
Precision Therapeutics in Lennox–Gastaut Syndrome: Targeting Molecular Pathophysiology in a Developmental and Epileptic Encephalopathy
by Debopam Samanta
Children 2025, 12(4), 481; https://doi.org/10.3390/children12040481 - 8 Apr 2025
Cited by 3 | Viewed by 1782
Abstract
Lennox–Gastaut syndrome (LGS) is a severe childhood-onset developmental and epileptic encephalopathy characterized by multiple drug-resistant seizure types, cognitive impairment, and distinctive electroencephalographic patterns. Current treatments primarily focus on symptom management through antiseizure medications (ASMs), dietary therapy, epilepsy surgery, and neuromodulation, but often fail [...] Read more.
Lennox–Gastaut syndrome (LGS) is a severe childhood-onset developmental and epileptic encephalopathy characterized by multiple drug-resistant seizure types, cognitive impairment, and distinctive electroencephalographic patterns. Current treatments primarily focus on symptom management through antiseizure medications (ASMs), dietary therapy, epilepsy surgery, and neuromodulation, but often fail to address the underlying pathophysiology or improve cognitive outcomes. As genetic causes are identified in 30–40% of LGS cases, precision therapeutics targeting specific molecular mechanisms are emerging as promising disease-modifying approaches. This narrative review explores precision therapeutic strategies for LGS based on molecular pathophysiology, including channelopathies (SCN2A, SCN8A, KCNQ2, KCNA2, KCNT1, CACNA1A), receptor and ligand dysfunction (GABA/glutamate systems), cell signaling abnormalities (mTOR pathway), synaptopathies (STXBP1, IQSEC2, DNM1), epigenetic dysregulation (CHD2), and CDKL5 deficiency disorder. Treatment modalities discussed include traditional ASMs, dietary therapy, targeted pharmacotherapy, antisense oligonucleotides, gene therapy, and the repurposing of existing medications with mechanism-specific effects. Early intervention with precision therapeutics may not only improve seizure control but could also potentially prevent progression to LGS in susceptible populations. Future directions include developing computable phenotypes for accurate diagnosis, refining molecular subgrouping, enhancing drug development, advancing gene-based therapies, personalizing neuromodulation, implementing adaptive clinical trial designs, and ensuring equitable access to precision therapeutic approaches. While significant challenges remain, integrating biological insights with innovative clinical strategies offers new hope for transforming LGS treatment from symptomatic management to targeted disease modification. Full article
(This article belongs to the Special Issue Childhood Epilepsy: Clinical Advances and Perspectives)
30 pages, 2381 KiB  
Article
Effects of Dietary Gamma-Aminobutyric Acid (GABA) Inclusion on Acute Temperature Stress Responses in Juvenile Olive Flounder (Paralichthys olivaceus)
by Abayomi Oladimeji Ogun, Haham Kim, Sooa Yoon, Suhyun Lee, Hyuncheol Jeon, Deni Aulia, Junhyeok Hur and Seunghyung Lee
Animals 2025, 15(6), 809; https://doi.org/10.3390/ani15060809 - 12 Mar 2025
Cited by 1 | Viewed by 1248
Abstract
This study investigated the potential of dietary gamma-aminobutyric acid (GABA) inclusion to mitigate acute temperature stress impacting the physiological resilience of juvenile olive flounder (Paralichthys olivaceus). A total of 360 juvenile fish, with an average initial weight of 12.97 ± 0.1 [...] Read more.
This study investigated the potential of dietary gamma-aminobutyric acid (GABA) inclusion to mitigate acute temperature stress impacting the physiological resilience of juvenile olive flounder (Paralichthys olivaceus). A total of 360 juvenile fish, with an average initial weight of 12.97 ± 0.1 g (mean ± SEM), were randomly assigned in triplicate to 18 tanks (20 fish per tank) and reared at 19.5 °C for 8 weeks, with bi-monthly collection of growth performance data. The fish were fed one of six experimental diets: control (GABA74), 174 ppm of GABA (GABA174), 275 ppm of GABA (GABA275), 396 ppm of GABA (GABA396), 476 ppm of GABA (GABA476), and 516 ppm of GABA (GABA516). At the end of the trial, one group of fish was subjected to lethal temperature stress (31 °C) for 48 h, while another was exposed to acute temperature stress (29 °C) for 6 h. Growth performance remained relatively stable across all inclusion levels (p > 0.05), with the final body weight (FBW) ranging from 48.2 ± 0.3 g (GABA174) to 50.3 ± 0.6 g (GABA516) and the feed conversion ratio (FCR) varying between 2.06 ± 0.07 (GABA396) and 2.35 ± 0.07 (control). There were no significant differences in average whole-body composition across all dietary treatments, with moisture content ranging from 74.8 to 75.0%, crude protein from 17.8 to 18.2%, crude lipid from 2.89 to 3.15%, and crude ash from 3.62 to 3.80%. Similarly, there were no significant differences in cumulative survival rates during lethal temperature exposure between the GABA-supplemented groups and the control group, with an average of 28.5 ± 4.6%. Additionally, GABA inclusion did not significantly alter plasma-free amino acid profiles, antioxidant enzyme activities, or immune functions (p > 0.05). However, temperature significantly reduced the levels of superoxide dismutase (SOD) from 3.34 ± 0.17 to 2.29 ± 0.36 µg/mL and increased the levels of glutamate oxaloacetate transaminase (GOT) from 17.1 ± 0.8 to 46.3 ± 6.2 U/L, glutamate pyruvate transaminase (GPT) from 14.4 ± 0.6 to 30.2 ± 2.1 U/L, glucose (GLU) from 13.3 ± 0.5 to 68.7 ± 7.7 mg/dL, total protein (TP) from 2.94 ± 0.00 to 3.21 ± 0.1 g/dL, and cortisol from 5001 ± 147 to 6395 ± 194 ng/mL. Furthermore, no significant changes were observed in the expression of key stress-related genes, including heat shock proteins (hsp60, hsp70, and hsp90) and the warm water acclimation-related gene wap65. This study establishes the safety of GABA as a dietary inclusion for olive flounder and highlights its potential to enhance stress resilience in aquaculture. However, the effectiveness of GABA-based interventions could depend on critical factors such as dosage, stress duration, and species-specific responses. Our findings highlight the need for further research to optimize GABA inclusion strategies, particularly with consideration for long-term physiological impacts. Full article
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21 pages, 11984 KiB  
Article
Gut Microbiota and Neurotransmitter Regulation: Functional Effects of Four Traditional Chinese Fermented Soybean (Sojae Semen Praeparatum)
by Lin Zhang, Huo Su, Siqi Wang, Yujie Fu and Manyuan Wang
Foods 2025, 14(4), 671; https://doi.org/10.3390/foods14040671 - 16 Feb 2025
Cited by 2 | Viewed by 1071
Abstract
This study aims to evaluate the potential disease prevention and treatment functions of four types of traditional Chinese fermented Sojae Semen Praeparatum (SSP) by analyzing their nutritional active components and their effects on the gut microbiota. Raw soybeans and the four SSPs were [...] Read more.
This study aims to evaluate the potential disease prevention and treatment functions of four types of traditional Chinese fermented Sojae Semen Praeparatum (SSP) by analyzing their nutritional active components and their effects on the gut microbiota. Raw soybeans and the four SSPs were administered as dietary supplements to normal SD rats for 6 weeks. Fecal samples were collected at weeks 0, 2, and 6 to assess changes in the gut microbiota. Our results revealed that different fermentation methods resulted in variations in soybean isoflavone content. Fermented soybeans promoted the growth of beneficial microorganisms associated with short-chain fatty acid production in the gut microbiota, such as Christensenellaceae_R_7_group, compared to unfermented soybeans. Supplementation with SSPs fermented with different processes increased the diversity of the rat gut microbiota, except for the fermented group of qingwenjiedu decoction (QW). The dominant gut microbiota in the fermented group of Artemisia Annuae Herba and Mori Folium (QS) exhibited anti-inflammatory effects, while the dominant gut microbiota in the fermented group of Ephedrae Herba and Perillae Folium (MZ) showed antidepressant effects. In the neurotransmitter analysis, MZ reduced gamma-aminobutyric acid (GABA) levels, the fermented group without Chinese medicine (DD) decreased dopamine levels, and both QS and QW increased norepinephrine levels. Correlation analysis highlighted connections between gut microbiota, neurotransmitters, and chemical levels. The results indicate that SSPs may contribute uniquely to health by maintaining intestinal balance and improving neurological disorders while predicting a potential association between neurotransmitters and gut microbiota by correlation analysis. Full article
(This article belongs to the Section Nutraceuticals, Functional Foods, and Novel Foods)
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17 pages, 1797 KiB  
Article
Dietary γ-Aminobutyric Acid Promotes Growth and Immune System Performance and Improves Erythropoiesis and Angiogenesis in Gibel Carp (Carassius auratus gibelio)
by Xinlan Bai, Lu Zhang, Hualiang Liang, Dongyu Huang, Mingchun Ren and Haifeng Mi
Animals 2025, 15(2), 125; https://doi.org/10.3390/ani15020125 - 7 Jan 2025
Viewed by 1342
Abstract
This experiment aimed to investigate the effect of dietary supplementation of γ-aminobutyric acid (GABA) on the growth performance, immune response, and oxygen-transport-related factors of Gibel carp (Carassius auratus gibelio). An eight-week culturing experiment was designed with five experimental diets, with the [...] Read more.
This experiment aimed to investigate the effect of dietary supplementation of γ-aminobutyric acid (GABA) on the growth performance, immune response, and oxygen-transport-related factors of Gibel carp (Carassius auratus gibelio). An eight-week culturing experiment was designed with five experimental diets, with the actual GABA content being 368 mg/kg (G1, control group), 449 mg/kg (G2), 527 mg/kg (G3), 602 mg/kg (G4), and 675 mg/kg (G5). The results showed that the level of 527 mg/kg (G3) of GABA significantly increased the specific growth rate (SGR), weight gain rate (WGR), and final body weight (FBW) of Gibel carp, while the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and glucose (GLU) were also increased significantly. In addition, 527 mg/kg (G3) and 602 mg/kg (G4) of GABA significantly increased the total antioxidant capacity (T-AOC). The mRNA expression of tnf-α, tgf-β, and il-10 was significantly increased at the level of 449 mg/kg (G2). In terms of oxygen-carrying capacity, the mRNA expression of epo, tf, tfr1, ho-1, and vegf was markedly increased at the level of 449 mg/kg (G2). In conclusion, dietary GABA supplementation can boost growth performance, enhance the immune system, and increase oxygen-carrying capacity in Gibel carp. Full article
(This article belongs to the Section Aquatic Animals)
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13 pages, 2322 KiB  
Article
Effects of Pretreatment Methods on Gamma-Aminobutyric Acid Enrichment and Quality Improvement in Highland Barley Beverages
by Xiaoqing Yin, Shanshan Wang, Zhirong Wang, Huaying Wen, Ting Bai and Yuhong Zhang
Foods 2024, 13(24), 4053; https://doi.org/10.3390/foods13244053 - 16 Dec 2024
Cited by 2 | Viewed by 1261
Abstract
Gamma-aminobutyric acid (GABA) is an important neurotransmitter that promotes sleep and reduces anxiety, but its natural synthesis in the body is insufficient, necessitating dietary intake. This study utilized a combination of germination, the addition of active barley powder, and fermentation to enhance GABA [...] Read more.
Gamma-aminobutyric acid (GABA) is an important neurotransmitter that promotes sleep and reduces anxiety, but its natural synthesis in the body is insufficient, necessitating dietary intake. This study utilized a combination of germination, the addition of active barley powder, and fermentation to enhance GABA content in an enzymatically hydrolyzed highland barley beverage. The samples were divided into five groups: highland barley (HB), germinated highland barley (GB), highland barley supplemented with another high-glutamic-acid decarboxylase-active highland barley powder TB13 (BT), germinated barley supplemented with TB13 (GBT), and germinated barley supplemented with TB13 followed by fermentation (GBTF). The results indicated that all the pretreatments significantly elevated GABA levels, with the GBT sample showing the highest GABA content, which was 2.4 times that of the HB sample. Germination had minimal impact on the taste and aroma of the beverage, while the addition of TB13 active barley powder caused only slight changes to the aroma. The GABA content in the GBTF sample was 2.2 times higher than in the HB sample, and the GBTF sample also exhibited the highest total phenolic content, demonstrating the strongest antioxidant and free-radical scavenging abilities. Furthermore, the GBTF treatment increased acidity, reduced bitterness, and significantly altered the flavor profile of the barley beverage, enhancing its overall quality and consumer appeal as a GABA-rich functional drink. Full article
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14 pages, 10481 KiB  
Article
Multi-Omics Reveal the Improvements of Nutrient Digestion, Absorption, and Metabolism and Intestinal Function via GABA Supplementation in Weanling Piglets
by Yan Zeng, Hong Hu, Yiwen He, Zhiying Deng, Yiting Guo and Xihong Zhou
Animals 2024, 14(22), 3177; https://doi.org/10.3390/ani14223177 - 6 Nov 2024
Cited by 1 | Viewed by 1412
Abstract
The nonprotein amino acid γ-aminobutyric acid (GABA) can enhance intestinal function in piglets; however, the mechanisms involved are not yet fully understood. To explore the effects of GABA and its underlying mechanisms, weanling piglets were randomly assigned to three groups, receiving either a [...] Read more.
The nonprotein amino acid γ-aminobutyric acid (GABA) can enhance intestinal function in piglets; however, the mechanisms involved are not yet fully understood. To explore the effects of GABA and its underlying mechanisms, weanling piglets were randomly assigned to three groups, receiving either a basal diet or a basal diet supplemented with GABA (80 mg/kg or 120 mg/kg). The results demonstrated that dietary GABA improved growth performance and reduced diarrhea incidence (p < 0.05). Additionally, GABA supplementation decreased the serum and intestinal levels of pro-inflammatory cytokines (p < 0.05), and improved intestinal morphology. Multi-omics analyses were employed to explore the alterations caused by GABA supplementation and elucidate the related mechanisms. Microbiota profiling revealed improved beta-diversity and changes in the composition of ileal bacteria and fungi. Amino acid metabolism, lipid metabolism, and digestive processes were primarily enriched in the GABA group according to metabolomics analysis. A transcriptome analysis showed significant enrichment in ion transmembrane transport and nutrition absorption and digestion pathways in the ileum. Furthermore, increased lipase and trypsin activity, along with the elevated expression of tight junction proteins confirmed the beneficial effects of GABA on intestinal nutrient metabolism and barrier function. In conclusion, dietary 80 mg/kg GABA supplementation improved nutrient digestion and absorption and intestinal function in weanling piglets. Full article
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15 pages, 859 KiB  
Article
Evaluation of Gamma Aminobutyric Acid and Sodium Butyrate in Juvenile Red Seabream (Pagrus major) Diets Containing Graded Levels of Fish Meal and Soy Protein Concentrate
by Buddhi E. Gunathilaka, Seong-Mok Jeong, Kang-Woong Kim, Seunghan Lee, Sang-Woo Hur, Sang-Guan You and Sang-Min Lee
Animals 2024, 14(13), 1973; https://doi.org/10.3390/ani14131973 - 3 Jul 2024
Cited by 1 | Viewed by 1381
Abstract
The experiment was conducted to evaluate the supplementary effects of gamma aminobutyric acid (GABA) and sodium butyrate (SB) when a graded level of fish meal (FM) was replaced with soy protein concentrate (SPC) in diets for juvenile red seabream (Pagrus major). [...] Read more.
The experiment was conducted to evaluate the supplementary effects of gamma aminobutyric acid (GABA) and sodium butyrate (SB) when a graded level of fish meal (FM) was replaced with soy protein concentrate (SPC) in diets for juvenile red seabream (Pagrus major). A control diet was designed to contain 60% FM (F60). Two other diets were formulated by reducing FM levels to 40% and 20% with SPC (F40 and F20). Six more diets were formulated by adding 0.02% GABA or 0.2% SB to each F60, F40 and F20 diets (F60G, F60S, F40G, F40S, F20G and F20S). Each diet was randomly assigned to a triplicate group of fish (5.52 g/fish) and provided for eight weeks. Final body weight, weight gain and specific growth rate of fish fed F60G, F60S, F40G and F40S diets were comparable and significantly higher (p < 0.05) than other groups. The growth of fish fed SB-containing diets was significantly increased (p < 0.05) compared to fish fed the respective control diets. The feed efficiency and protein efficiency ratios were significantly higher (p < 0.05) in the fish fed all diets containing 60% and 40% FM compared to F20 and F20G groups. The F40S diet resulted in the highest feed utilization values. The F20S group exhibited significantly higher (p < 0.05) feed utilization than the F20 and F20G groups. Serum lysozyme activity was significantly higher (p < 0.05) in fish fed the GABA- and SB-containing diets compared to the F20 group. The F60S group exhibited the highest lysozyme activity which was significantly higher (p < 0.05) than in the F20 and F40 groups. Therefore, the growth performance, feed utilization and innate immunity of red seabream can be enhanced by dietary supplementation with GABA or SB in low-FM diets containing SPC. The FM level in the juvenile red seabream diet can be reduced to 40% with SPC and GABA or SB while maintaining performance better than a diet containing 60% FM. Full article
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13 pages, 1165 KiB  
Article
A Comparison of Phenolic, Flavonoid, and Amino Acid Compositions and In Vitro Antioxidant and Neuroprotective Activities in Thai Plant Protein Extracts
by Pontapan Polyiam and Wipawee Thukhammee
Molecules 2024, 29(13), 2990; https://doi.org/10.3390/molecules29132990 - 23 Jun 2024
Cited by 6 | Viewed by 2725
Abstract
The leaves of mulberry, Azolla spp., sunflower sprouts, cashew nut, and mung bean are considered rich sources of plant protein with high levels of branched-chain amino acids. Furthermore, they contain beneficial phytochemicals such as antioxidants and anti-inflammatory agents. Additionally, there are reports suggesting [...] Read more.
The leaves of mulberry, Azolla spp., sunflower sprouts, cashew nut, and mung bean are considered rich sources of plant protein with high levels of branched-chain amino acids. Furthermore, they contain beneficial phytochemicals such as antioxidants and anti-inflammatory agents. Additionally, there are reports suggesting that an adequate consumption of amino acids can reduce nerve cell damage, delay the onset of memory impairment, and improve sleep quality. In this study, protein isolates were prepared from the leaves of mulberry, Azolla spp., sunflower sprouts, cashew nut, and mung bean. The amino acid profile, dietary fiber content, phenolic content, and flavonoid content were evaluated. Pharmacological properties, such as antioxidant, anticholinesterase, monoamine oxidase, and γ-aminobutyric acid transaminase (GABA-T) activities, were also assessed. This study found that concentrated protein from mung beans has a higher quantity of essential amino acids (52,161 mg/100 g protein) compared to concentrated protein from sunflower sprouts (47,386 mg/100 g protein), Azolla spp. (42,097 mg/100 g protein), cashew nut (26,710 mg/100 g protein), and mulberry leaves (8931 mg/100 g protein). The dietary fiber content ranged from 0.90% to 3.24%, while the phenolic content and flavonoid content ranged from 0.25 to 2.29 mg/g and 0.01 to 2.01 mg/g of sample, respectively. Sunflower sprout protein isolates exhibited the highest levels of dietary fiber (3.24%), phenolic content (2.292 ± 0.082 mg of GAE/g), and flavonoids (2.014 mg quercetin/g of sample). The biological efficacy evaluation found that concentrated protein extract from sunflower sprouts has the highest antioxidant activity; the percentages of inhibition of 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and 2,2′-azino-bis-(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical were 20.503 ± 0.288% and 18.496 ± 0.105%, respectively. Five plant-based proteins exhibited a potent inhibition of acetylcholinesterase (AChE) enzyme activity, monoamine oxidase (MAO) inhibition, and GABA-T ranging from 3.42% to 24.62%, 6.14% to 20.16%, and 2.03% to 21.99%, respectively. These findings suggest that these plant protein extracts can be used as natural resources for developing food supplements with neuroprotective activity. Full article
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14 pages, 635 KiB  
Article
Evaluation of Gamma-Aminobutyric Acid (GABA) as a Functional Feed Ingredient on Growth Performance, Immune Enhancement, and Disease Resistance in Olive Flounder (Paralichthys olivaceus) under High Stocking Density
by Jinho Bae, Mohammad Moniruzzaman, Hyeong-Woo Je, Seunghan Lee, Wonsuk Choi, Taesun Min, Kang-Woong Kim and Sungchul C. Bai
Antioxidants 2024, 13(6), 647; https://doi.org/10.3390/antiox13060647 - 25 May 2024
Cited by 4 | Viewed by 2685
Abstract
Gamma-aminobutyric acid (GABA) is a non-protein amino acid that is found in the brain and central nervous system of animals as an inhibitory neurotransmitter. It has been shown to have a variety of physiological functions, including stress reduction and immune enhancement. This study [...] Read more.
Gamma-aminobutyric acid (GABA) is a non-protein amino acid that is found in the brain and central nervous system of animals as an inhibitory neurotransmitter. It has been shown to have a variety of physiological functions, including stress reduction and immune enhancement. This study investigated the effects of dietary supplementation with GABA on growth, serum biochemistry, innate immunity, and disease resistance in juvenile olive flounders (Paralichthys olivaceus) challenged with Edwardsiella tarda under high-stocking density. A control diet and three experimental diets were prepared, with 150 mg/kg (GABA150), 200 mg/kg (GABA200), and 250 mg/kg (GABA250) of GABA added to each diet, respectively. Each experimental diet was fed to olive flounders in triplicate with an initial weight of 12.75 g ± 0.3 g in 40 L tanks at two stocking densities: normal density (20 fish/tank) and high density (40 fish/tank). After 8 weeks of the feeding trial, growth, feed utilization, whole-body proximate compositions, blood analyses, and non-specific immune responses were measured, and challenge tests were performed. There were no significant differences in the weight gain (WG) and specific growth rate (SGR) among fish fed the GABA-supplemented diets at the two stocking densities. However, the normal-density groups showed significantly higher WG and SGR than the high-density groups (p < 0.05). There was no significant difference in feed efficiency and protein efficiency ratio among all groups. Moreover, there was no significant difference in the whole-body proximate composition analysis (p > 0.05). There were no significant differences in cortisol levels in fish fed the GABA at both densities, but the high-density group showed a significantly higher cortisol than the low-density group. Blood GABA significantly increased in a dose-dependent manner regardless of the density groups (p < 0.05). Superoxide dismutase activity showed significantly higher levels than the control group, but there was no significant effect of the stocking densities in fish fed the GABA diets (p < 0.05). Myeloperoxidase activities in fish fed the GABA200 and GABA250 diets showed significantly higher levels at both of the stocking densities (p < 0.05). Lysozyme activity was significantly higher in the GABA150 group than in the CON, GABA200, and GABA250 groups (p < 0.05). After 15 days of challenge tests with Edwardsiella tarda, the cumulative survival rates of the GABA150, GABA200, and GABA250 groups were significantly higher than that of the CON group (p < 0.05). The results suggested that the optimal dietary GABA level for juvenile olive flounder culture is 150 mg/kg, regardless of rearing density, to enhance growth, immunity, and disease resistance. Full article
(This article belongs to the Special Issue Antioxidants Benefits in Aquaculture 2.0)
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19 pages, 949 KiB  
Review
The Effect of Oral GABA on the Nervous System: Potential for Therapeutic Intervention
by Shahad Almutairi, Amaya Sivadas and Andrea Kwakowsky
Nutraceuticals 2024, 4(2), 241-259; https://doi.org/10.3390/nutraceuticals4020015 - 6 May 2024
Cited by 15 | Viewed by 32145
Abstract
Gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system (CNS), plays a pivotal role in maintaining the delicate balance between inhibitory and excitatory neurotransmission. Dysregulation of the excitatory/inhibitory balance is implicated in various neurological and psychiatric disorders, emphasizing the critical [...] Read more.
Gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system (CNS), plays a pivotal role in maintaining the delicate balance between inhibitory and excitatory neurotransmission. Dysregulation of the excitatory/inhibitory balance is implicated in various neurological and psychiatric disorders, emphasizing the critical role of GABA in disease-free brain function. The review examines the intricate interplay between the gut–brain axis and CNS function. The potential impact of dietary GABA on the brain, either by traversing the blood–brain barrier (BBB) or indirectly through the gut–brain axis, is explored. While traditional beliefs questioned GABA’s ability to cross the BBB, recent research challenges this notion, proposing specific transporter systems facilitating GABA passage. Animal studies provide some evidence that small amounts of GABA can cross the BBB but there is a lack of human data to support the role of transporter-mediated GABA entry into the brain. This review also explores GABA-containing food supplements, investigating their impact on brain activity and functions. The potential benefits of GABA supplementation on pain management and sleep quality are highlighted, supported by alterations in electroencephalography (EEG) brain responses following oral GABA intake. The comprehensive overview encompasses GABA’s sources in the diet, including brown rice, soy, adzuki beans, and fermented foods. GABA’s presence in various foods and supplements, its association with gut microbiota, and its potential as a therapeutic strategy for neurological disorders are thoroughly examined. The articles were retrieved through a systematic review of the databases: OVID, SCOPUS, and PubMed (keywords “GABA”, “oral GABA“, “sleep”, “cognition”, “neurodegenerative”, “blood-brain barrier”, “gut microbiota”, “supplements” and “therapeutic”, and by searching reference sections from identified studies and review articles). This review presents the relevant literature available on the topic and discusses the mechanisms, effects, and hypotheses that suggest oral GABA benefits range from neuroprotection to blood pressure control. The literature suggests that oral intake of GABA affects the brain illustrated by changes in EEG scans and cognitive performance, with evidence showing that GABA can have beneficial effects for multiple age groups and conditions. The potential clinical and research implications of utilizing GABA supplementation are vast, spanning a spectrum of diseases ranging from neurodegeneration to blood pressure regulation. Importantly, recommendations for the use of oral GABA should consider the dosage, formulation, and duration of treatment as well as potential side effects. Effects of GABA need to be more thoroughly investigated in robust clinical trials to validate efficacy to progress the development of alternative treatments for a variety of disorders. Full article
(This article belongs to the Special Issue The Role of Nutraceuticals in Central Nervous System Disorders)
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