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LWT-FOOD SCIENCE AND TECHNOLOGY · 2016 · IF 2.711

Improvement in beta-carotene, vitamin B2, GABA, free amino acids and isoflavones in yellow and black soybeans upon germination

Guocheng Huang,Weixi Cai,Baojun Xu

There is a lack of information on the various components in germinated soybeans. Therefore, this study aimed to further investigate the differences between three-day -germinated and raw (non-germinated) yellow and black soybeans. The results showed that germination increased the contents of beta-carotene and vitamin B 2 significantly. The free amino acids in raw soybeans were not detected but determined in germinated soybeans, which illustrated that the total free amino acids in germinated soybeans were higher than in raw soybeans. Meanwhile, GABA was 10-fold increased in germinated soybeans. The increase of aglycones of isoflavones was significantly high that reached to over 700% in both soybeans. The total saponin content in germinated yellow soybeans was increased two times whereas there was a slight decline in germinated black soybeans. The anthocyanin content was found to be declined in germinated black soybeans. The current study indicates that three-day- germinated soybeans yield higher nutritional values than raw soybeans, suggesting that the germinated soybeans are a good source of various nutrients and other biologically active compounds.

CAS / MDL: 103-72-0
研究领域: 营养学 · 食品科学 · 植物生理学
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PEST MANAGEMENT SCIENCE · 2023 · IF 4.1

Functional validation of A2′N mutation of the RDL GABA receptor against fipronil via molecular modeling and genome engineering in drosophila

Xiaomu Qiao,Tianhao Zhou,Jing Zhang,Lixin Zhang,Yaobin Lu,Jia Huang

BACKGROUND Insect RDL (resistant to dieldrin) receptors are essential pentameric ligand-gated chloride channels that mediate the neuroinhibitory effect of GABA, the chief inhibitory neurotransmitter in the central nervous system. These receptors serve as primary targets for various insecticides, including noncompetitive antagonists (NCAs) such as cyclodiene organochlorines and phenylpyrazoles, as well as allosteric modulators like meta-diamides and isoxazolines. This study focuses on a newly discovered A2′N mutation within the RDL receptors, identified in fipronil-resistant planthoppers. Despite in vitro electrophysiological studies have proposed its role in conferring target-site resistance, in vivo genetic functional validation of this mutation remains unexplored. RESULTS Our research employed toxicity bioassays, assessing various Rdl genotypes against a spectrum of insecticides, including fipronil, α-endosulfan, broflanilide, and isocycloseram. Results revealed distinct resistance profiles for A2′N and A2′S mutants, indicating different binding interactions of RDL receptors with NCAs. Significantly, the A2′N heterozygote showed substantial resistance to fipronil, despite its homozygous lethality. Molecular modeling and docking simulations further supported these findings, highlighting unique binding poses for fipronil and α-endosulfan. CONCLUSION This study confirmed that A2′N mutation of the RDL GABA receptor confer high resistance to fipronil in vivo . The observed resistance in A2′N mutants is likely attributable to a steric hindrance mechanism, wherein the introduction of larger side chains hampers fipronil binding, even in a heterozygous state. © 2023 Society of Chemical Industry.

CAS / MDL: 959-98-8 120068-37-3
研究领域: 昆虫学 · 神经生物学 · 毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Immunology · 2017 · IF 6.429

Intestinal Microbiota-Derived GABA Mediates Interleukin-17 Expression during Enterotoxigenic Escherichia coli Infection

Ren Wenkai,Yin Jie,Xiao Hao,Chen Shuai,Liu Gang,Tan Bie,Li Nengzhang,Peng Yuanyi,Li Tiejun,Zeng Benhua,Li Wenxia,Wei Hong,Yin Zhinan,Wu Guoyao,Hardwidge Philip R.,Yin Yulong

Intestinal microbiota has critical importance in pathogenesis of intestinal infection; however, the role of intestinal microbiota in intestinal immunity during enterotoxigenic Escherichia coli (ETEC) infection is poorly understood. The present study tested the hypothesis that the intestinal microbiota is associated with intestinal interleukin-17 (IL-17) expression in response to ETEC infection. Here, we found ETEC infection induced expression of intestinal IL-17 and dysbiosis of intestinal microbiota, increasing abundance of γ-aminobutyric acid (GABA)-producing Lactococcus lactis subsp. lactis. Antibiotics treatment in mice lowered the expression of intestinal IL-17 during ETEC infection, while GABA or L. lactis subsp. lactis administration restored the expression of intestinal IL-17. L. lactis subsp. lactis administration also promoted expression of intestinal IL-17 in germ-free mice during ETEC infection. GABA enhanced intestinal IL-17 expression in the context of ETEC infection through activating mechanistic target of rapamycin complex 1 (mTORC1)-ribosomal protein S6 kinase 1 (S6K1) signaling. GABA–mTORC1 signaling also affected intestinal IL-17 expression in response to Citrobacter rodentium infection and in drug-induced model of intestinal inflammation. These findings highlight the importance of intestinal GABA signaling in intestinal IL-17 expression during intestinal infection and indicate the potential of intestinal microbiota-GABA signaling in IL-17-associated intestinal diseases.

CAS / MDL: 56-12-2 16338-48-0
研究领域: 微生物学 · 免疫学 · 病理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2024 ·Vol. 25 ·期 18 ·10033 · IF 4.9

Effects of GABA on Oxidative Stress and Metabolism in High-Glucose Cultured Mongolian Sheep Kidney Cells

Rina Su,Longwei Chang,Tong Zhou,Fanhua Meng,Dong Zhang

The Mongolian sheep, emblematic of the Inner Mongolian grasslands, is renowned for its exceptional stress resistance and adaptability to harsh environments, drawing considerable attention. Recent research has unveiled the novel role of γ-aminobutyric acid (GABA) in combating oxidative stress. This investigation examined how GABA impacts renal-cortex and medulla cells from Mongolian sheep exposed to high-glucose stress conditions, utilizing gene expression analysis and non-targeted metabolomics. Elevated glucose levels significantly reduced the viability of Mongolian sheep renal cells and increased reactive oxygen species (ROS) levels. Conversely, the introduction of GABA notably enhanced cell viability, reduced ROS production, and stimulated the expression of antioxidant genes (e.g.,Gpx,SOD,CAT) in the renal cortex. In the renal medulla,CATexpression increased, whileGpxgene expression showed mixed responses. Metabolomics analysis indicated that high-glucose exposure altered various metabolites, whereas GABA alleviated the metabolic stress induced by high glucose through modulating glycolysis and the tricarboxylic acid cycle. In Mongolian sheep renal cells, GABA effectively mitigated oxidative damage triggered by high-glucose stress by upregulating antioxidant genes and regulating metabolic pathways, revealing insights into its potential mechanism for adapting to extreme environments. This finding offers a fresh perspective on understanding the stress resilience of Mongolian sheep and may provide valuable insights for research across diverse disciplines.

CAS / MDL: 64-18-6
研究领域: 动物生理学 · 细胞生物学 · 分子生物学 · 代谢组学 · 应激生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Toxicologie Analytique et Clinique · 2025 · IF 1.7

Simultaneous detection and quantification of a novel imidazole-derived GABA agonist isopropoxate and etomidate acid from human urines in abused cases by LC-MS/MS

Xiaolong Zhang,Kundi Zhao,Yuxuan Chen,Jinlei Liu,Jie Gu,Mengchao Wang,Yinyin Dai,Huimin Zhang,Amin Wurita,Koutaro Hasegawa

Summary Introduction Distribution of imidazole-derived GABA agonists, such as etomidate, metomidate and its analogs have been encountered frequently especially in China, along with its abuse cases. Recently, we were enquired to investigate urine samples and dubious powder seized from abuse cases, in which a new etomidate analog isopropoxate was detected. Methods The etomidate analog contained in the seized powder was tried to be identified using gas chromatography-mass spectrometry and by hydrolysis its ester structure to related alcohol under basic reaction environment, as a preliminary analysis for the powder composition. Reference standard were then purchased to identify the compound in suspected powder. For urine samples, after adding the internal standard and acetonitrile to the urine samples followed by vortexing and centrifugation, the supernatant layer was analyzed by LC-MS/MS. Results For LC-MS/MS analysis, the coefficient of determination (r2) values of the calibration curves of etomidate acid and isopropoxate in the urine were more than 0.99; the limits of detection (LODs) for etomidate acid, and isopropoxate was 0.025   ng/mL; the limits of quantification (LOQs) of them was 0.05   ng/mL. Etomidate acid and isopropoxate could be determined from submitted urines. And nine isopropoxate metabolites and their major metabolic pathways were identified. Conclusions In this study, we have established a simultaneous and reliable analytical method for etomidate acid and isopropoxate in human urine by LC-MS/MS, and the method could be applied to authentic cases. It is also the first time that the metabolic pathway of isopropoxate in the human body has been explored.

CAS / MDL: 56649-48-0
研究领域: 毒理学 · 分析化学 · 法医学
✓ 已验证 产品关联 DOI 高影响因子
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2023 · IF 6.1

Physiological Function of RDL1 and RDL2 Subunits of the Ionotropic GABA Receptor in the Spodoptera litura with the CRISPR/Cas9 System In Vivo

Zhong Qiang Jia,Su Gui Zhang,Ying Wang,Jun Heng Pan,Fei Fan Liu,En Ling Zhan,Eman Atef Fouad,Ya Li Fu,Qi Rui Pan,Chun Qing Zhao

In insect ionotropic γ-aminobutyric acid receptor (iGABAR) subunits, only resistance to dieldrin (RDL) can be individually and functionally expressed in vitro. In lepidopteran, two to three RDL subtypes are identified; however, their physiological roles have not been distinguished in vivo. In this study, SlRdl1 and SlRdl2 of S. litura were individually knocked out using CRISPR/Cas9, respectively. The mortality and larval and pupal duration of KOSlRdl1 and KOSlRdl2 were increased. The flight time and distance were increased by 43.30%–80.66% and 58.96%–198.22%, respectively, in KOSlRdl1. The GABA-induced current was significantly decreased by 53.57%–74.28% and 46.91%–63.34% in the ventral nerve cord, and the GABA titer was significantly reduced by 17.65%–28.05% and 19.85%–42.46% in KOSlRdl1 and KOSlRdl2, respectively. In conclusion, SlRdl1 and SlRdl2 are necessary for the transmission of GABA-induced neural signals; however, only SlRdl1 could regulate the flight capability of S. litura. Our results provided a new avenue to study lepidopteran iGABARs.

CAS / MDL: 56512-49-3
研究领域: 昆虫学 · 分子生物学 · 神经科学 · 基因工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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LWT-FOOD SCIENCE AND TECHNOLOGY · 2024 · IF 6

Comprehensive analysis reveals the contribution of “rolling-anaerobic” processing to the improved aroma, taste and color of GABA black tea

Dongzhu Huang,Hong Wang,Yuhan Wu,Chenyi Sun,Maoyin Fu,Ying Zhang,Yunqiu Yang,Xiaochun Wan,Yeyun Li,Qi Chen

GABA black tea (GABT), produced by the combination of anaerobic treatment and Chinese traditional black tea processing technology, has a unique flavor and health benefits. However, how to manufacture high-quality GABT efficiently is the major challenge for this area. In this study, a processing improvement of multiple rolling-anaerobic treatment cycle was applied to prepare tailored GABTs, and their comprehensive quality including aroma, taste and color were analyzed. The sensory evaluation results showed that the improvement significantly optimized the overall GABT quality. The accumulation of linalool oxide Ⅰ, citronellol, etc. was the main reason for the superior aroma of tailored GABT, while the dynamic changes of sweet/umami amino acids, catechins and tea pigments played critical roles in the GABT taste and color quality formation during processing. Furthermore, correlation analysis was applied to determine the contribution of various processing steps. These findings provide a novel manufacturing method for high-quality GABT products.

CAS / MDL: 71-36-3
研究领域: 食品科学 · 茶叶加工 · 感官评价
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2025 · IF 8.5

The alleviation of pear chilling injury by chitosan-based coating during long term refrigeration is related to respiratory path, ethylene biosynthesis, and GABA shunt

Yiqin Zhang,Huanqi Wu,Wanli Zhang,Yaowen Liu,Weibo Jiang,Wen Qin

Long-term cold storage usually induces chilling injury of pear fruits. This study investigated the effects of CTS/SiO 2 -GABA (Chitosan/Silicon dioxide-γ-Aminobutyric acid) coating on alleviating chilling injury in pears during long-term refrigeration (1 °C). Results showed that GABA significantly improved the mechanical properties of CTS-based films, attributable to amidation, Maillard reaction, and non-covalent crosslinking between CTS and GABA, which offset the undesirable effects of SiO 2 . Specifically, the values of tensile strength and elongation at break of CTS/SiO 2 -GABA film increased to 23.95 MPa and 78.13 %, respectively. These enhanced crosslinked structures also contributed to the water resistance behavior of CTS/SiO 2 -GABA film, that is, the moisture content, water solubility and water vapor permeability reduced to 20.38 %, 25.49 % and 0.86 g·s −1 ·m −1 ·Pa −1 ·10 −7 respectively, and the water contact angle increased to 50.47°. Additionally, CTS/SiO 2 -GABA coating effectively maintained the quality of pears, including weight loss (4.38 %), firmness (6.24 kg·mm −2 ), peel yellowing (1.40 of Δa*), core browning, sugars/acids balance. Mechanistically, CTS/SiO 2 -GABA coating regulated the metabolic flux in respiratory pathways of pears (suppress glycolysis and tricarboxylic acid cycle, enhance pentose phosphate pathway), by inhibiting ethylene biosynthesis and enhancing GABA shunt metabolism. This study provides a novel perspective on the regulatory mechanism of functional coatings to improve postharvest fruit quality.

CAS / MDL: 7631-86-9 56-12-2
研究领域: 采后生物学 · 园艺学 · 植物生理学 · 食品科学 · 分子生物学 · 代谢调控
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Pharmacology · 2024 · IF 4.4

Activation of GABA type A receptor is involved in the anti-insomnia effect of Huanglian Wendan Decoction

Li Liang,Wu Xiaorong,Gong Jili,Wang Zhuqiang,Dai Weibo,Qiu Li,Zuo Hongyuan,Yi Mengqin,Yuan Hui,Hu Mei,Gao Zhaobing,Tian Fuyun

Huanglian Wendan Decoction (HWD) is a traditional Chinese medicine (TCM) prescribed to patients diagnosed with insomnia, which can achieve excellent therapeutic outcomes. As positively modulating the γ-aminobutyric acid (GABA) type A receptors (GABAARs) is the most effective strategy to manage insomnia, this study aimed to investigate whether the activation of GABAARs is involved in the anti-insomnia effect of HWD. We assessed the metabolites of HWD using LC/MS and the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and tested the pharmacological activity in vitro and in vivo using whole-cell patch clamp and insomnia zebrafish model. In HEK293 cells expressing α1β3γ2L GABAARs, HWD effectively increased the GABA-induced currents and could induce GABAAR-mediated currents independent of the application of GABA. In the LC-MS (QToF) assay, 31 metabolites were discovered in negative ion modes and 37 metabolites were found in positive ion modes, but neither three selected active metabolites, Danshensu, Coptisine, or Dihydromyricetin, showed potentiating effects on GABA currents. 62 active metabolites of the seven botanical drugs were collected based on the TCMSP database and 19 of them were selected for patch-clamp verification according to the virtual docking simulations and other parameters. At a concentration of 100 μM, GABA-induced currents were increased by (+)-Cuparene (278.80% ± 19.13%), Ethyl glucoside (225.40% ± 21.77%), and β-Caryophyllene (290.11% ± 17.71%). In addition, (+)-Cuparene, Ethyl glucoside, and β-Caryophyllene could also serve as positive allosteric modulators (PAMs) and shifted the GABA dose-response curve (DRC) leftward significantly. In the PCPA-induced zebrafish model, Ethyl glucoside showed anti-insomnia effects at concentrations of 100 μM. In this research, we demonstrated that the activation of GABAARs was involved in the anti-insomnia effect of HWD, and Ethyl glucoside might be a key metabolite in treating insomnia.

CAS / MDL: 73-31-4
研究领域: 中医药学 · 神经药理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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NEUROPHARMACOLOGY · 2017 · IF 5.012

Recombinant tissue plasminogen activator induces long-term anxiety-like behaviors via the ERK1/2-GAD1-GABA cascade in the hippocampus of a rat model

Mei-Xue Dong,Chen-Meng Li,Peng Shen,Qing-Chuan Hu,You-Dong Wei,Yi-Fei Ren,Jia Yu,Si-Wen Gui,Yi-Yun Liu,Jun-Xi Pan,Peng Xie

Objectives Recombinant tissue plasminogen activator (rtPA) is widely used for patients with thromboembolic disease , and increasing evidence indicates that it can directly induce neurotoxicity independent of its thrombolysis property. Here, we aimed to confirm the long-term effect of rtPA on animal's behavior , and investigate the underlying pathogenesis. Methods and results Male Sprague-Dawley rats randomly received a dose of rtPA (10 mg/kg) or sterile saline. Three months later, the animals receiving rtPA displayed anxiety-like behaviors in the open field and novelty-suppressed feeding tests. To investigate the possible pathogenesis, gas chromatography-mass spectrometry-based metabolomics analysis was performed, with 18 differential metabolites identified in the hippocampus 24 h after the treatments. Based upon these differential metabolites, a metabolite-protein integrated network was generated, which indicated that ERK1/2-glutamic acid decarboxylase (GAD) 1-γ aminobutyric acid (GABA) cascade may be related to long-term anxiety-like behaviors. The GABA levels in hippocampus were decreased 24 h post-treatment and three months later, confirmed by a high performance liquid chromatography method. We also examined the expression of GAD1 and GAD2 using western blotting or immunohistochemical staining . Levels of GAD1 were persistently decreased after treatment, while GAD2 levels, GAD1-immunoreactive, and GAD2-immunoreactive neurons showed no significant differences. The underlying pathogenesis also involved activation of ERK1/2, confirmed by increased phospho-ERK1/2 24 h post-treatment. Conclusions RtPA can induce long-term anxiety-like behaviors after a clinical injected dose. The underlying pathogenesis involves the ERK1/2-GAD1-GABA cascade in the hippocampus. This pharmacological side effect of rtPA may further exacerbate post-stroke anxiety disorder for stroke patients.

CAS / MDL: 643-79-8
研究领域: 神经科学 · 药理学 · 行为科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Forensic Toxicology · 2024 · IF 2.8

Identification of a novel imidazole-derived GABA agonist isopropoxate: simultaneous detection and quantification of imidazole-derived analogs from human hairs in abused cases by LC–MS/MS

Zhang Xiaolong,Chen Yuxuan,Liu Jinlei,Wang Mengchao,Dai Yinyin,Zhao Kundi,Gu Jie,Zhang Huimin,Wurita Amin,Hasegawa Koutaro

Purpose Distribution and abuse of imidazole-derived γ-aminobutyric acid (GABA) agonists, such as etomidate and metomidate, and their analogs have been encountered frequently especially in China. The aim of this study was to identify etomidate, metomidate, propoxate, and isopropoxate more accurately by establishing a gas chromatography–mass spectrometry (GC–MS) and liquid chromatography tandem mass spectrometry (LC–MS/MS) method and applying it to real forensic cases. Methods One mg of the seized powder was dissolved in 1 mL of methanol, and subjected to GC–MS and LC–MS/MS. Hair samples were washed and cut into approximately 2 mm sections, then ground to powder by a low-temperature grinder. Twenty mg of the hair powder was extracted with 1 mL of methanol, and the supernatant was subjected to LC–MS/MS. Results Etomidate, metomidate, propoxate, and isopropoxate were chromatographically separated and each mass spectrum was obtained by GC–MS. For LC–MS/MS, tested validation data were all satisfactory. The seized powder samples contained isopropoxate, with an approximate content of 30.9%. Etomidate, etomidate acid, metomidate, and isopropoxate could be determined in the submitted hairs, ranging from 2.89 to 8.09 ng/mg, 0.0591–0.177 ng/mg, 0.342–2.77 ng/mg, and 33.2–130 ng/mg, respectively. Conclusions Mass spectra and ion chromatograms of etomidate, metomidate, isopropoxate, and propoxate were obtained by GC–MS. We have also established a simultaneous and reliable analytical method for etomidate, etomidate acid, metomidate, and isopropoxate in human hair by LC–MS/MS. This is the first report to present analytical results of a novel imidazole-derived GABA agonist isopropoxate in drug abuse cases.

CAS / MDL: 56649-48-0
研究领域: 法医学 · 药物滥用检测 · 分析化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Animals · 2024 ·Vol. 14 ·期 22 ·3177 · IF 2.7

Multi-Omics Reveal the Improvements of Nutrient Digestion, Absorption, and Metabolism and Intestinal Function via GABA Supplementation in Weanling Piglets

Yan Zeng,Hong Hu,Yiwen He,Zhiying Deng,Yiting Guo,Xihong Zhou

Simple SummaryAs a nonprotein amino acid, γ-aminobutyric acid (GABA) plays a vital role in intestinal function. This study aimed to investigate the underlying mechanisms by which GABA affects intestinal health in piglets. The results showed that GABA significantly improved growth performance, reduced diarrhea, and mitigated inflammation. Additionally, microbiota profiling revealed enhanced diversity and changes in the composition of ileal bacteria and fungi. Metabolomic and transcriptomic analyses suggested that dietary supplementation with GABA could affect several pathways related to nutrient digestion and absorption. We further confirmed that GABA increased the activities of lipase and trypsin, as well as elevated the expression of tight junction proteins. Therefore, we propose that dietary 80 mg/kg GABA supplementation may enhance nutrient digestion and absorption, thereby improving intestinal function in weanling piglets.AbstractThe 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.

CAS / MDL: 56-12-2
研究领域: 动物科学 · 营养学 · 微生物学 · 分子生物学 · 生物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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