ARCHIV DER PHARMAZIE
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2019
·Vol. 352
·期 8
·1800313
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IF 2.145
Ming-Xia Song,Yuping Huang,Shiben Wang,Zeng-Tao Wang,Xian-Qing Deng
A novel series of benzoxazole derivatives containing 1,2,4-triazolone ( 5a-m ) was designed. These compounds were synthesized in order to screen their anticonvulsant activities by the maximal electroshock seizure (MES) model and the subcutaneous pentylenetetrazole (sc-PTZ) seizure model in mice. The rotarod test was used to evaluate their neurotoxicities. Most of the compounds showed anti-MES activities at 100 and 300 mg/kg. Compound 5f , which showed potential anticonvulsant activity in the MES model with ED 50 values of 22.0 mg/kg, was considered as the most promising one in this study. It exhibited greater safety than that of carbamazepine and valproate regarding neurotoxicity. The efficacy of compound 5f in inhibiting the tonic seizures and death induced by the convulsants 3-mercaptopropionic acid and BIC was also verified. In an enzyme-linked immunosorbent assay, compound 5f and the positive drug phenytoin significantly increased the γ-aminobutyric acid (GABA) level in the mouse brain. Further, pretreatment with an inhibitor of the GABA synthesizing enzyme dramatically raised the ED 50 value of 5f in the MES model. These results confirmed that the compound 5f plays its anticonvulsive action via regulating the GABA function in the brain. Also, a docking study of the compound 5f in the benzodiazepine (BZD) binding site of the GABA A receptor confirmed possible binding of the compound 5f with BZD receptors.
研究领域:
药理学
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神经科学
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DOI
PubMed
高影响因子
Cell and Bioscience
·
2023
·Vol. 13
·期 1
·1-20
·
IF 7.5
Liu Xing-Yang,Wang Ke,Deng Xian-Hua,Wei Yi-Hua,Guo Rui,Liu Sui-Feng,Zhu Yi-Fan,Zhong Jia-Jun,Zheng Jing-Yuan,Wang Meng-Dan,Ye Qiu-Hong,He Jian-Quan,Guo Kai-Hang,Zhu Jun-Rong,Huang Shu-Qiong,Chen Ze-Xu,Lv Chong-Shan,Wen Lei
Background Olfactory dysfunction is among the earliest non-motor symptoms of Parkinson’s disease (PD). As the foremost pathological hallmark, α-synuclein initiates the pathology in the olfactory pathway at the early stage of PD, particularly in the olfactory epithelium (OE) and olfactory bulb (OB). However, the local neural microcircuit mechanisms underlying olfactory dysfunction between OE and OB in early PD remain unknown.Results We observed that odor detection and discrimination were impaired in 6-month-old SNCA-A53T mice, while their motor ability remained unaffected. It was confirmed that α-synuclein increased and accumulated in OB but not in OE. Notably, the hyperactivity of mitral/tufted cells and the excitation/inhibition imbalance in OB were found in 6-month-old SNCA-A53T mice, which was attributed to the impaired GABAergic transmission and aberrant expression of GABA transporter 1 and vesicular GABA transporter in OB. We further showed that tiagabine, a potent and selective GABA reuptake inhibitor, could reverse the impaired olfactory function and GABAergic signaling in OB of SNCA-A53T mice.Conclusion sTaken together, our findings demonstrate potential synaptic mechanisms of local neural microcircuit underlying olfactory dysfunction at the early stage of PD. These results highlight the critical role of aberrant GABAergic signaling of OB in early diagnosis and provide a potential therapeutic strategy for early-stage PD.
研究领域:
神经科学
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药理学
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疾病模型
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DOI
PubMed
高影响因子
POSTHARVEST BIOLOGY AND TECHNOLOGY
·
2026
·
IF 7.3
Zhiquan Wang,Junchao Wang,Lu Qin,Zhen Huang,Xinxin Xu,Zhifeng Zhu,Jingjie Tang,Xiaojie Cui,Rangwei Xu,Feng Zhu,Yanping Fu,Xiuxin Deng,Quan Sun,Yunjiang Cheng
Postharvest wax coating reduces water loss and enhances visual appeal but impairs gas exchange in citrus fruit, inducing anaerobic fermentation and off-flavor development. This study demonstrates that exogenous γ-aminobutyric acid (GABA) mitigates these physiological disorders. GABA enhanced peel gas permeance by 1.7- to 2.2-fold through suppression of C25-C31 cuticular alkane biosynthesis and enlargement of stomatal apertures, thereby alleviating internal hypoxia. This metabolic shift from anaerobic fermentation toward aerobic respiration was mediated by GABA shunt reprogramming and amino acid metabolic remodeling, which reduced ethanol accumulation by 57% while preserving key flavor compounds. Transcriptomic analysis revealed coordinated regulation of genes associated with wax synthesis, fermentation, and hypoxia responses. This simple amino acid treatment preserves citrus fruit flavor and nutritional quality under waxing-induced hypoxia by mitigating physiological disorders.
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高影响因子
BIOCHEMICAL ENGINEERING JOURNAL
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2023
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IF 3.9
Juanjuan Ding,Wenyan Ba,Shengping You,Wei Qi,Rongxin Su
γ-aminobutyric acid (GABA) is an important inhibitory neurotransmitter in the brain with many physiological functions. Therefore, this work establishes an efficient biosynthesis process to achieve the high production of food-grade GABA. Firstly, we adopted a directional colorimetric screening method and then obtained the strain Lactobacillus brevis ( Lb. brevis) CGMCC 24975 with 22.61 g/L GABA in shake flasks, much higher than Lb. brevis ATCC 367 (3.07 g/L) due to its more efficient and stable expression of its glutamate decarboxylase (GAD) system. After exploring the effects of optimal fermentation conditions and oxygen on GABA production, we found that anaerobic fermentation could increase GABA production by up-regulating gad operon expression and activating GADase. Finally, we developed an oil-sealed anaerobic fermentation process with 157.90 g/L GABA in a 5 L bioreactor, which was 6.98-fold of that in shake flasks. This work includes a complete process from screening GABA-producing strains to developing efficient fermentation processes, laying the foundation for producing food-safe GABA.
研究领域:
微生物学
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生物技术
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食品科学
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DOI
高影响因子
Foods
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2025
·Vol. 15
·期 1
·71
·
IF 5.1
Shufeng Yin,Yiyao Wang,RuiXue Zhao,Ning Zhao,Hao Liu,Yining Tang,Ningbo Qin,Yiwei Dai,Xinping Lin
Inoculated fermentation can enhance the flavor, nutrition, and functionality of juice. The lactic acid bacteria (LAB) are commonly used as starter cultures. This study screened LAB for orange juice fermentation and optimized fermentation factors using response surface methodology (RSM) to improve GABA content in orange juice. A total of 52 LAB strains were screened, andLacticaseibacillus paracaseiZY (Lcb. paracaseiZY) andLacticaseibacillus rhamnosusSN12 (Lcb. rhamnosusSN12) presented higher GABA yields and adaptability to substrates. The optimized fermentation factors for GABA enhancement in orange juice were as follows: initial pH of 5.5, fermentation temperature of 37 °C, soluble solids content of 12.0 °Bx, inoculum ratio ofLcb. paracaseiZY toLcb. rhamnosusSN12 as 1:1, inoculum size of 6 Log CFU/mL, and fermentation time of 96 h. Under these optimized conditions, the GABA content reached 0.89 g/L, representing a 39.06% increase compared to uninoculated orange juice. This indicates that RSM-based optimization is conducive to increasing GABA content in orange juice and provides a scientific basis for the development of GABA-enriched functional fermented juices.
研究领域:
食品科学与技术
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微生物学
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功能食品
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生物加工
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产品关联
DOI
PubMed
高影响因子
CELL PROLIFERATION
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2023
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IF 8.5
Juanyu Zhou,Li He,Mengyou Liu,Xiaoxin Guo,Gang Du,La Yan,Zehong Zhang,Zhendong Zhong,Haiyang Chen
Sleep is essential for maintaining health. Indeed, sleep loss is closely associated with multiple health problems, including gastrointestinal disorders. However, it is not yet clear whether sleep loss affects the function of intestinal stem cells (ISCs). Mechanical sleep deprivation and sss mutant flies were used to generate the sleep loss model. qRT-PCR was used to measure the relative mRNA expression. Gene knock-in flies were used to observe protein localization and expression patterns. Immunofluorescence staining was used to determine the intestinal phenotype. The shift in gut microbiota was observed using 16S rRNA sequencing and analysis. Sleep loss caused by mechanical sleep deprivation and sss mutants disturbs ISC proliferation and intestinal epithelial repair through the brain–gut axis. In addition, disruption of SSS causes gut microbiota dysbiosis in Drosophila . As regards the mechanism, gut microbiota and the GABA signalling pathway both partially played a role in the sss regulation of ISC proliferation and gut function. The research shows that sleep loss disturbed ISC proliferation, gut microbiota, and gut function. Therefore, our results offer a stem cell perspective on brain–gut communication, with details on the effect of the environment on ISCs.
研究领域:
神经科学
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细胞生物学
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分子生物学
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微生物学
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DOI
PubMed
高影响因子
eLife
·
2024
·
IF 6.4
Fangyan Wang,Xiujie Liu,Furong Huang,Yan Zhou,Xinyu Wang,Zhengyang Song,Sisi Wang,Xiaoting Wang,Dibang Shi,Gaoyi Ruan,Xiawei Ji,Eryao Zhang,Zenglin Tan,Yuqing Ye,Chuang Wang,Jesse Zhu,Wantie Wang
Hepatic ischemia/reperfusion injury (HIRI) is a common and inevitable factor leading to poor prognosis in various liver diseases, making the outcomes of current treatments in clinic unsatisfactory. Metformin has been demonstrated to be beneficial to alleviate HIRI in recent studies, however, the underpinning mechanism remains unclear. In this study, we found metformin mitigates HIRI-induced ferroptosis through reshaped gut microbiota in mice, which was confirmed by the results of fecal microbiota transplantation treatment but showed the elimination of the beneficial effects when gut bacteria were depleted using antibiotics. Detailedly, through 16S rRNA and metagenomic sequencing, we identified that the metformin-reshaped microbiota was characterized by the increase of gamma-aminobutyric acid (GABA) producing bacteria. This increase was further confirmed by the elevation of GABA synthesis key enzymes, glutamic acid decarboxylase and putrescine aminotransferase, in gut microbes of metformin-treated mice and healthy volunteers. Furthermore, the benefit of GABA against HIRI-induced ferroptosis was demonstrated in GABA-treated mice. Collectively, our data indicate that metformin can mitigate HIRI-induced ferroptosis by reshaped gut microbiota, with GABA identified as a key metabolite.
研究领域:
药理学
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胃肠病学
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分子生物学
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微生物学
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DOI
PubMed
高影响因子
BEHAVIOURAL NEUROLOGY
·
2023
·
IF 2.8
Lijuan Chen,Jing Li,Xinglian Liu,Zhiwei Zhao,Yan Jin,Yikun Fu,Aiqin Zhou,Chengqun Wang,Yan Zhou
Vitamin B6 (VB6) exhibits therapeutic effects towards autism spectrum disorder (ASD), but its specific mechanism is poorly understood. Rat dams were treated with VB6 standard, VB6 deficiency, or VB6 supplementary diet, and the same treatment was provided to their offspring, with their body weights monitored. Three-chambered social test and open field test were employed to evaluate the effect of VB6 on autism-like behaviors. Gamma-aminobutyric acid (GABA) generation and synaptic inhibition of neurons in the hippocampus of rat were detected via immunofluorescence staining, followed by the measurement of GABA concentration through high-performance liquid chromatography (HPLC). The role of VB6 in the autophagy and apoptosis of cells was determined via Western blot and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). In order to conduct rescue experiments, the inhibition of mammalian target of rapamycin (mTOR) or the activation of GABA was achieved by drug administration to the offspring rats with VB6 deficiency. As a result, no evident difference in weight was observed in the offspring with varied VB6 treatments. VB6 deficiency impaired social interaction; aggravated self-grooming and bowel frequency; decreased GABA concentration, VIAAT, GAD67, vGAT expressions, and LC3 II/LC3 I ratio; increased p62 level and p-mTOR/mTOR ratio; and promoted cell apoptosis. Inhibition of mTOR reversed the effect of VB6 deficiency on cell autophagy. GABA activation or mTOR inhibition offset the role of VB6 deficiency in autism-like behaviors and hippocampal GABA expression. Collectively, VB6 deficiency induces autism-like behaviors in rats by regulating mTOR-mediated autophagy in the hippocampus.
研究领域:
神经科学
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药理学
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行为科学
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分子生物学
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DOI
PubMed
高影响因子
METABOLIC BRAIN DISEASE
·
2022
·Vol. 37
·期 8
·2883-2901
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IF 3.655
Jiang Chuan,Wang Hua,Qi Jiaying,Li Jinghan,He Qianqian,Wang Chaonan,Gao Yonggang
Cherry leaves ( Prunus pseudocerasus Lindl. [Rosaceae] ), a traditional Chinese herbal medicine, can regulate the factors closely related to depression including inflammatory cytokines, oxidative stress and blood glucose level. However, the antidepressant effects of cherry leaves and underlying neuromodulatory mechanisms remain relatively have not been elucidated explicitly. The present study investigated the antidepressant effects of cherry leaf decoction (CLD). The underlying neuromodulatory mechanism was explored by examining the glutamate (Glu)/γ-aminobutyric acid (GABA)-glutamine (Gln) metabolic loop. The chronic unpredictable mild stress (CUMS) rodent model was used in this study. The main flavonoids components of CLD were identified using high-performance liquid chromatography (HPLC). The antidepressant effects of CLD were assessed throughout behavioural tests including the bodyweight, sucrose preference test (SPT), forced swimming test (FPT) and tail suspension test (TST). Moreover, The baseline levels of serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were quantified. The expression of proteins integrally involved in the Glu/GABA-Gln metabolic loop were observed and quantified by Western blotting, reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. This study found that CLD ameliorated depressive-like behaviours induced by CUMS. The increase of serum ACTH and CORT baseline levels induced by CUMS was also reversed after CLD intervention. Furthermore, CUMS reduced the expression of GAD65, GAD67, GLT-1, GS and GABA A and increased NMDAR1 levels in the rat hippocampus, which was normalized by CLD treatment. The findings demonstrated that CLD could ameliorate the depression-like behaviours induced by CUMS, potentially through the inhibition of hypothalamic–pituitary–adrenal (HPA) axis hyperactivity and the regulation of Glu/GABA-Gln metabolic loop. Graphical abstract
研究领域:
药理学
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神经科学
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传统中药
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行为科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2024
·
IF 3.3
Fengjin He,Yanfang Yan,Mei Peng,Ming Gao,Lang Zhou,Faju Chen,Lishou Yang,Liangqun Li,Xiaosheng Yang
BACKGROUND Insomnia, a prevalent sleep disorder, detrimentally affects quality of life and is often challenging to manage with conventional treatments. This study delved into identifying and quantifying the main compounds by employing ultra-performance liquid chromatography–Q-Exactive-Orbitrap mass spectrometry, and further to evaluate the therapeutic potential of Rosa roxburghii folium (RRF) extract, with multiple pharmacological activities. Previous research had hinted at the efficacy of glycosides in influencing the γ -aminobutyric acid (GABAergic) system, which plays a pivotal role in sleep regulation. Utilizing a p -chlorophenylalanine-induced insomnia model in BALB/C mice, this investigation aimed to unravel the effects of various dosages of RRF extract on sleep quality and elucidated its mechanism of action. RESULTS A total of 66 compounds in the RRF extract were analyzed. Behavioral assessments demonstrated notable enhancements in sleep duration and latency. Biochemical analyses further corroborated these findings, revealing modulation in neurotransmitter levels indicative of a potential mechanism through the GABAergic and serotoninergic pathways. Additionally, histological evaluations suggested anti-inflammatory and antioxidant effects of the RRF extract. CONCLUSION The findings from this study underscored the therapeutic efficacy of RRF extract in combating insomnia, particularly highlighting its glycoside components’ role. The extract's significant improvement in sleep duration and latency, alongside its modulation of neurotransmitter levels, showcases its potential as a natural remedy for insomnia. Through its action on the GABAergic and serotoninergic pathways, as well as its anti-inflammatory and antioxidant effects, RRF extract emerges as a promising candidate for insomnia treatment, offering a holistic approach to sleep disorder management. © 2024 Society of Chemical Industry.
研究领域:
药理学
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神经科学
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睡眠障碍
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天然疗法
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生物化学
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DOI
PubMed
高影响因子
Food Science and Technology
·
2023
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IF 2.602
LIU Xu,WANG Jun,XU Zihan,SUN Jianfeng,LIU Yaqiong,XI Xiaoli,MA Yanli
In this research, a total of 47 samples from five types of fermented soybeans were selected. The physicochemical parameters, biogenic amines (BAs) and bioactive compounds such as isoflavones, total phenolic (TPC) and γ-aminobutyric acid (GABA) were investigated. The results showed that the contents of isoflavones ranged from 598.06 mg/kg to 2725.03 mg/kg in all samples and it varied from 598.96 mg/kg to 2241.67 mg/kg in Semen Sojae Preparatum (SSP) which was higher than other types of fermented soybeans. The maximum variation of GABA content was found in Aspergillus-type douchi (AD) samples. The maximum value of TPC in SSP was 4.53 g/kg. For BAs, the indicator of spoilage, 4.26% of fermented soybeans samples may lead to histamine poisoning and 42.55% of samples with total BAs contents exceeding 100 mg/kg may be harmful to human body. It indicated that different types of fermented soybeans had various bioactive compounds and BAs, so different fermented soybeans could be selected according to bioactive substances. This finding could provide comprehensive information of health beneficial compounds and BAs risks of fermented soybeans. It could guide consumers to select healthy, nutritious and safety fermented soybeans.
研究领域:
食品科学
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营养学
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化学分析
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毒理学
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产品关联
DOI
高影响因子
Pharmaceuticals
·
2024
·Vol. 17
·期 9
·1161
·
IF 4.3
Luge Chen,Yingwei Liu,Dawei Xu,Na Zhang,Yong Chen,Jin Yang,Lijuan Sun
With the increasing prevalence of insomnia-related diseases, the effective treatment of insomnia has become an important health research topic. Lavender (Lavandula angustifoliaMill.) essential oil (LEO) is a commonly used medicine for the treatment of insomnia and neurological disorders. However, neither the active components nor its sedative–hypnotic mechanism have been fully discovered. This study aimed to screen the main active terpenes and discover the possible mechanism of LEO through network pharmacology in the treatment of insomnia-related diseases, as well as to verify our hypothesis in insomnia mice. The results showed that, in LEO’s 15 potential active ingredients, beta-myrcene had strong sedative–hypnotic effects through the serotonergic synaptic pathway according to the network pharmacological prediction. Further, PCPA(DL-4-chlorophenylalanine)-induced insomnia mice were treated with beta-myrcene for one day or seven days. The quiet state of insomnia mice was increased effectively, and the hypnotic effect was enhanced by anaobarbital sodium by prolonging sleep duration, decreasing sleep latency, and increasing the rate of falling asleep. Beta-myrcene reduced the damage to hypothalamic neuron cells induced by PCPA and increased neurotransmitter levels of GABA, 5-HT, and Glu in the serum and hypothalamus of insomnia mice. Meanwhile, beta-myrcene exerted an improvement in insomnia by upregulating relevant genes and protein expression in the serotonergic synaptic pathway. These results support the merit of the sedative–hypnotic activity of LEO. Beta-myrcene, a terpene in LEO, may be the main source of its sedative–hypnotic properties. It may serve as a good potential compound in future clinical studies on coping with insomnia.
研究领域:
药理学
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神经科学
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医学
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DOI
PubMed
高影响因子
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