ARCHIV DER PHARMAZIE
·
2024
·
IF 4.3
Xianghao Zeng,Shaobing Cheng,Huilan Li,Haiyang Yu,Yushun Cui,Yuanying Fang,Shilin Yang,Yulin Feng
Alzheimer's disease (AD) is a multifactorial neurological disease, and the multitarget directed ligand (MTDL) strategy may be an effective approach to delay its progression. Based on this strategy, 27 derivatives of l -tryptophan, 3a-1–3d-1 , were designed, synthesized, and evaluated for their biological activity. Among them, IC 50 (inhibitor concentration resulting in 50% inhibitory activity) values of compounds 3a-18 and 3b-1 were 0.58 and 0.44 μM for human serum butyrylcholinesterase ( h BuChE), respectively, and both of them exhibited more than 30-fold selectivity for human serum acetylcholinesterase. Enzyme kinetics studies showed that these two compounds were mixed inhibitors of h BuChE. In addition, these two derivatives possessed extraordinary antioxidant activity in OH radical scavenging and oxygen radical absorption capacity fluorescein assays. Meanwhile, these compounds could also prevent β-amyloid (Aβ) self-aggregation and possessed low toxicity on PC12 and AML12 cells. Molecular modeling studies revealed that these two compounds could interact with the choline binding site, acetyl binding site, and peripheral anionic site to exert submicromolar BuChE inhibitory activity. In the vitro blood–brain barrier permeation assay, compounds 3a-18 and 3b-1 showed enough blood–brain barrier permeability. In drug-likeness prediction, compounds 3a-18 and 3b-1 showed good gastrointestinal absorption and a low risk of human ether-a-go-go-related gene toxicity. Therefore, compounds 3a-18 and 3b-1 are potential multitarget anti-AD lead compounds, which could work as powerful antioxidants with submicromolar selective inhibitory activity for h BuChE as well as prevent Aβ self-aggregation.
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高影响因子
TALANTA
·
2015
·
IF 3.545
Bingdi Liu,Xiaoqian Ouyang,Yaping Ding,Liqing Luo,Duo Xu,Yanqun Ning
In the present work, transition metal oxides decorated graphene (GR) have been fabricated for simultaneous determination of dopamine (DA), acetaminophen (AC) and tryptophan (Trp) using square wave voltammetry . Electro-deposition is a facile preparation strategy for the synthesis of nickel oxide (NiO) and copper oxide (CuO) nanoparticles . GR can be modified by using citric acid to produce more functional groups, which is conducive to the deposition of dispersed metal particles. The morphologies and interface properties of the obtained NiO–CuO/GR nanocomposite were examined by scanning electron microscopy, energy dispersive X-ray spectroscopy and Raman spectroscopy. Moreover, the electrochemical performances of the composite film were investigated by cyclic voltammetry and electrochemical impedance spectroscopy . The modified electrode exhibited that the linear response ranges for detecting DA, AC and Trp were 0.5–20 μM, 4–400 μM and 0.3–40 μM, respectively, and the detection limits were 0.17 μM, 1.33 μM and 0.1 μM ( S / N =3). Under optimal conditions, the sensor displayed high sensitivity, excellent stability and satisfactory results in real samples analysis.
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高影响因子
Nanoscience and Nanotechnology Letters
·
2017
·Vol. 9
·期 11
·1700-1707
·
IF 1.889
Zou Jiao,Huang Lele,Jiang Xinyu,Jiao Feipeng,Yu Jingang
A novel chiral electrochemical sensor was fabricated and used for recognition of tryptophan (Trp) enantiomers. Graphene oxide (GO) was prepared by the modified Hummers' method. Moreover, the suspensions/solutions of GO, bovine serum albumin (BSA) and chitosan (CS) in deionized-distilled
water were coated onto the surface of GCE by a layer-by-layer drop method, and the novel triple layered GO/BSA/CS composite modified glassy carbon electrode (GO/BSA/CS/GCE) was fabricated. The electrochemical recognition and quantification of the Trp enantiomers on the GO/BSA/CS/GCE
were performed using differential pulse voltammetry (DPV). The Trp monomer concentrations exhibited a good linear relationship with the peak current values. The GO/BSA/CS/GCE exhibited good coefficients of determination (R
2
D-Trp
= 0.98917 and R
2
L-Trp
= 0.94824) for D- and L-Trp enantiomers in the concentration range of 1 to 8 mM, respectively. The GO/BSA/CS/GCE fabricated in this study exhibited superior recognition performance, good oxidation potential and current response signals for D- and L-Trp. The novel GO/BSA/CS/GCE
fabricated in this study exhibited potential to be used as a convenient, fast and efficient chiral electrochemical sensor for qualitative and quantitative determination of Trp enantiomers.
研究领域:
分析化学
·
生物化学
·
电化学传感器
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BMC Complementary Medicine and Therapies
·
2025
·Vol. 26
·期 1
·9
·
IF 3.4
Zhu Liangting,Hu Junjie,Li Juan,Qu Xinyue,Zhou Xian,Gan Guoping,Liu Yanwen,Liu Songlin,Chen Xin
Background Sini San (SNS) is a traditional Chinese medicinal formulation originating from the “ Treatise on Febrile Diseases ”, an ancient text that has been historically employed for treating depression. However, the underlying mechanisms by which SNS potentially ameliorates symptoms of depression remain unclear. This study aimed to elucidate the role of gut microbiota in tryptophan metabolism and examine the involvement of short-chain fatty acids (SCFAs) in the putative antidepressant effects of SNS. Methods A rat model of depression using chronic unpredictable mild stress (CUMS) was established through simultaneous modeling and treatment for six consecutive weeks. The possible therapeutic effect of SNS on CUMS-induced rats was thoroughly assessed using body weight measurements, open-field tests, and sucrose preference tests. Alterations in rat gut microbiota were analyzed using full-length 16 S rRNA third-generation sequencing. Furthermore, metabolomic analysis was performed on fecal samples. An enzyme-linked immunosorbent assay (ELISA) was used to quantify tryptophan (Trp), serotonin (5-HT), and kynurenine (Kyn) in the hippocampal and colonic tissues. Reverse transcription quantitative PCR (RT-qPCR) was used to measure the mRNA levels of TPH-1 and TPH-2 in hippocampal and colonic tissues. Immunofluorescence was used to assess hippocampal IDO-1 and IBA-1 expression. Finally, gas chromatography-mass spectrometry (GC-MS) was used to analyze the SCFAs content in fecal samples. Results Administration of SNS significantly alleviated depressive symptoms induced by CUMS, as demonstrated by increased body weight, improved sucrose preference, and a statistically significant decrease in immobility time during the forced swim test ( P < 0.05). The Shannon and Simpson indices were elevated following SNS treatment, signifying an enhancement in both the quantity and variety of the gut microbiota. Analysis using 16 S rRNA gene sequencing revealed that SNS influenced the composition of the gut microbiome, favorably increasing the presence of beneficial bacteria, such as Firmicutes , Lactobacillaceae , Ruminococcaceae , and Oscillospiraceae , while simultaneously decreasing the levels of potentially detrimental bacteria, such as Muribaculaceae , Prevotellaceae , Lachnospiraceae , and Alloprevotella . Fecal metabolomic studies identified 87 metabolites, of which 57 were differentially expressed, most notably l-tryptophan and phenylalanine. These metabolites were primarily linked to 15 metabolic pathways, with notable enrichment in the biosynthetic pathways of phenylalanine, tyrosine, and tryptophan, as well as the metabolic pathways of arachidonic acid and phenylalanine. Metabolomic profiling indicated that SNS stimulated the kynurenine pathway, leading to increased levels of metabolites with antidepressant properties, such as Trp, 5-HT, and Kyn, in both hippocampal and colonic tissues. In addition, SNS promoted the synthesis of SCFAs, particularly butyrate and propionate, which are known for their neuroprotective properties. Conclusions The present study suggests that the antidepressant effects of SNS can be attributed to its ability to modulate the structure of the gut microbiota, consequently regulating tryptophan metabolism and SCFA levels, which ultimately ameliorate symptoms of depression. These findings provide experimental evidence supporting the concept of the brain-gut axis in depression treatment and lay a foundation for further investigation of the underlying antidepressant mechanisms of the SNS.
研究领域:
药理学
·
神经科学
·
微生物组研究
·
中医中药
·
代谢组学
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高影响因子
FOOD CHEMISTRY
·
2026
·
IF 9.8
Zhihao Liu,Fu Zhao,Qihao Li,Qixiang Shang,Daozheng Fang,Xinyue Li,Haimeng Li,Quanrun He,Dapeng Zhang,Juanjuan Cheng,Yong Zhu,Zhongxia Li,Ana Sanches Silva,Jihang Chen
Ellagic acid (EA) is a dietary polyphenol with limited systemic bioavailability, resulting in substantial intestinal exposure. However, the biochemical mechanisms by which EA modulates gut microbiota and metabolism remain unclear. Here, EA improved glucose tolerance and enhanced insulin sensitivity, with histology confirming reduced lipid accumulation and restored tissue architecture in liver, skeletal muscle, brown adipose tissue, and mesenteric fat. Consistently, metagenomic analysis showed that EA enriched Akkermansia muciniphila , Muribaculum intestinale , and Duncaniella dubosii , while reducing Lachnoclostridium phocaeense . These microbial shifts were accompanied by elevated levels of tryptophan-derived metabolites—indole-3-propionic acid, indole, and indole-3-acrylic acid—known to enhance insulin sensitivity. Lipidomic revealed EA decreased triacylglycerols and ceramides, along with restored phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine levels. Transcriptomic revealed EA suppressed hepatic lipogenesis, inhibited MAPK signaling in skeletal muscle, activated thermogenic and oxidative phosphorylation in adipose tissues. Our findings highlight EA as a food-derived polyphenol that alleviates insulin resistance through a gut microbiota–indole metabolite–multi-tissue axis.
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高影响因子
ANALYTICA CHIMICA ACTA
·
2021
·
IF 6.558
Tao Gong,Shu Zhu,Suqiong Huang,Pengcheng Gu,Yan Xiong,Jing Zhang,Xinhui Jiang
Molecular self-assembly provides a reasonably effective strategy for the design and construction of chiral sensors. Here, Cu 2+ was connected to β-cyclodextrin (β-CD) through coordination to synthesize Cu 2 -β-CD, subsequently assembled with ammoniated chitosan-MWCNTs (NH 2 -CS-MWCNTs) by the effect of coordination driver to form a chiral sensing interface Cu 2 -β-CD/NH 2 -CS-MWCNTs. Using the electrochemical method, the valid recognition of tryptophan (Trp) isomers was achieved on the self-assembly interface. Under the optimal experimental conditions, the developed sensor exhibited good linearity and satisfactorily renewable ability. Cu 2 -β-CD/NH 2 -CS-MWCNTs/GCE showed the capacity to predict the ratio of D-Trp and L-Trp in racemic mixtures and the possibility of qualitative and quantitative determination for Trp isomers. Finally, the electrochemical sensor was used to detect the Trp enantiomers in rat serum, further verifying the feasibility of the sensor in the determination of actual samples. Therefore, the electrochemical chiral sensor not only is used for the recognition of Trp enantiomers but shows great potential in practical applications.
研究领域:
电化学
·
手性传感
·
分析化学
·
纳米材料
·
生物传感器
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高影响因子
ELECTROANALYSIS
·
2023
·Vol. 36
·期 2
·e202300237
·
IF 3
Toleshi Teshome,Shimeles Addisu Kitte,Abera Gure,Guta Gonfa
The co-precipitation approach was employed in this study to create Fe doped ZnO (Fe-ZnO) nanoparticles (NPs). To characterize the synthesized NPs, Ultra violet-Visible (UV-Vis) spectroscopy, X-ray diffraction (XRD), fourier transform infrared (FT-IR), scanning electron microscopy (SEM), and Brunauer-Emmett-Teller (BET) were used. Here, a novel electrochemical approach for the detection of tryptophan (Trp) using a glassy carbon electrode modified with Fe-ZnO NPs (Fe-ZnO/GCE) is demonstrated. The research findings revealed that Fe-ZnO/GCE enhanced the electron transfer rate of Trp oxidation. The sensitivity of Trp detection using Fe-ZnO/GCE in phosphate buffer solution (PBS) at pH 64.0 was significantly improved compared to bare GCE due to the electrocatalytic activity of Fe-ZnO NPs. Fe-ZnO/GCE exhibited a linear response with Trp concentrations ranging from 0.1 to 150 μM with the limit of detection (LOD) is 0.089 μM (3σ /m ) and limit of quantification (LOQ) about 0.3 μM (10σ /m ) using linear sweep voltammetry (LSV). The Fe-ZnO/GCE sensor was also effectively used to detect Trp in African catfish and multivitamin tablets. Trp analysis in real samples exhibited good recovery values of 89.60 to 99.15 %, demonstrating the accuracy and practicality of the method.
研究领域:
分析化学
·
生物医学工程
·
材料科学
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JOURNAL OF THE ELECTROCHEMICAL SOCIETY
·
2016
·Vol. 163
·期 7
·B272
·
IF 3.014
Hao Gou,Jingxian He,Zunli Mo,Xiaojiao Wei,Rere Hu,Yawen Wang,Ruibin Guo
A fast electrochemical chiral sensor based on L-lysine (L-Lys) covalent functionalize reduced graphene oxide (RGO) has been developed for electrochemical recognize of tryptophan (Trp) enantiomers. The reduced graphene oxide/L-Lys (RGO/L-Lys) chiral composites with excellent water-soluble and biocompatible is very suitable for electrochemical sensor. Meanwhile, the L-Lys retains original chirality in RGO/L-Lys composites, which progress to electrochemical chiral sensor. Cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) were implemented to monitor the electrochemical behavior when RGO/L-Lys simply modified on glassy carbon electrode (RGO/L-Lys/GCE). Surprisingly, the reduction of peak current was significantly different after the RGO/L-Lys composites interacted with L-Trp or D-Trp, and the testing time is very short. It suggested that the RGO/L-Lys/GCE can be used as an electrochemical chiral sensor for the discrimination of Trp enantiomers. In this electrochemical discrimination process, the three-point interaction between L-Lys and Trp enantiomers has played an important role. Further research indicated that the decreased of peak currents versus percentage of L-Trp of Trp racemic mixture exhibits a fine linear relationship, it provides opportunity to make analysis for discrimination of Trp enantiomers. The RGO/L-Lys/GCE electrochemical chiral sensor with rapid recognition, good sensitivity and high stability provided an efficient method to recognize and determine Trp enantiomers.
研究领域:
分析化学
·
生物化学
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高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2026
·
IF 6.8
Xiaoyu Wan,Yuanyu Wu,Yanan Sun,Yuxuan Liu,Guoliang Jia
DAS pretreatment protected mice against DSS-induced colitis. • DAS restored tight junctions and suppressed inflammatory injury. • DAS reshaped the gut microbiota toward a protective profile. • DAS increased indole-producing tryptophan metabolites, especially IPA and IAld. Ethnopharmacological relevance Allium sativum L. has a long-standing use in traditional medicine for gastrointestinal disorders. Diallyl sulfide (DAS), a key organosulfur compound derived from garlic, exhibits anti-inflammatory activity; however, its specific role in colitis and the underlying microbiota–metabolite mechanisms remain unresolved. Materials and methods Colitis was induced in mice using DSS following DAS pretreatment. Disease severity, intestinal barrier integrity, inflammation, gut microbiota composition, tryptophan metabolites, AhR signaling, colonic IL-22 levels, and STAT3 phosphorylation were evaluated. Fecal microbiota transplantation (FMT), IPA/IAld supplementation, parallel pharmacodynamic comparisons, and AhR blockade with CH223191 were executed to explore the microbiota–metabolite–host signaling axis. Results DAS pretreatment conferred protection against DSS-induced colitis, evidenced by reduced disease activity, preserved colon length, improved histological injury, suppressed inflammatory responses, and restored tight-junction proteins. DAS modified the gut microbiota and elevated local intestinal levels of IPA and IAld. FMT and IPA/IAld supplementation partially recapitulated the protective phenotype associated with DAS, while combined supplementation of IPA + IAld yielded broader protective effects, nearing the protective outcomes provided by DAS. AhR blockade via CH223191 diminished DAS-mediated protection, characterized by decreases in AhR and Cyp1a1 expression, colonic IL-22 levels, and the p-STAT3/STAT3 ratio. Conclusion DAS pretreatment offers prophylactic protection against DSS-induced colitis by altering the gut microbiota and enhancing local indole-producing tryptophan metabolism, effects mediated at least in part by the AhR/IL-22/STAT3 pathway. Download: Download high-res image (215KB) Download: Download full-size image
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Journal of Environmental Sciences
·
2025
·
IF 6.3
Mengxing Cui,Shilin Chen,Zhihan Zhang,Yongjiang Yu,Yingxi Xu,Ludi Liu,Huan Gao,Xiaoyu Chen,Ziqi Liu,Xue Zhang,Wenke Yuan,Shen Chen,Daochuan Li,Liping Chen,Xiumei Xing,Yongmei Xiao,Wen Chen,Yan Liu,Qing Wang
The global incidence of inflammatory bowel disease (IBD) has been escalating. Recent studies have identified co-exposure to polystyrene nanoplastics (PSNP) and triclosan (TCS), two prevalent environmental pollutants, as emerging risk factors for IBD. However, the molecular mechanisms contributing to its deteriorative effect remain elusive. To explore the mechanisms, we conducted an integrative analysis of metagenomic and metabolomic data in a mouse model of colitis induced by dextran sulfate sodium (DSS) following co-exposure to PSNP and TCS. Results demonstrated that co-exposure to PSNP and TCS significantly exacerbated DSS-induced colitis, as evidenced by elevated disease activity indices and pro-inflammatory cytokine levels. Mechanistically, this aggravation correlated with a marked reduction in Akkermansia muciniphila abundance, which was further associated with the disruption of tryptophan metabolism. Specifically, the disruption of this metabolic pathway led to decreased production of two key tryptophan-derived metabolites: indole acetic acid (IAA) and indole acetamide (IAM). In-vitro experiments confirmed that co-exposure to PSNP and TCS inhibited the growth of Akkermansia muciniphila rather than affecting the integrity of intestinal epithelial cells. Additionally, IAA and IAM reduced inflammatory cytokine secretion in THP-1 cells. These findings suggest that the reduction in Akkermansia muciniphila abundance might decrease the production of IAA and IAM by disrupting tryptophan metabolism. This disruption ultimately contributes to the inflammatory response induced by co-exposure to PSNP and TCS. Our study offers a novel insight into microbiota-host interactions and potential therapeutic targets for intestinal disease.
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高影响因子
Food Bioscience
·
2026
·
IF 6.2
Haomin Zhou,Zhangming Pei,Ning Wang,Zhifeng Fang,Wenbing Hu,Hongchao Wang,Wenwei Lu,Hao Zhang,Wei Chen
Atopic dermatitis (AD) is a chronic, recurrent inflammatory skin disorder of global significance. Long-term use of conventional treatments like topical corticosteroids is associated with adverse effects and a substantial economic burden. Building on prior work demonstrating that specific probiotic strains and a tailored dietary fiber combination ameliorate AD in mice by modulating gut microbiota-derived tryptophan metabolites via the gut-skin axis, but the precise bioactive indoles and their underlying mechanisms remain elusive. Here, we induced AD in mice using 2,4-dinitrofluorobenzene and administered five representative indole derivatives via intragastric gavage. Disease amelioration was assessed through ear swelling quantification, histopathological analysis, enumeration of infiltrated mast cells, and measurement of serum IgE and cytokines by ELISA. Only indole-3-acetaldehyde (IAId) and indole-3-lactic acid (ILA) markedly attenuated AD pathology, reducing ear swelling by over 30% alongside decreased skin thickness and mast cell infiltration. Immunomodulatory profiling revealed these metabolites downregulated IL-4, IL-13, and TSLP expression by 25%–40% and upregulated IFN-γ production by 50%, thereby restoring the Th1/Th2 immune balance. To dissect the mechanism, we employed an aryl hydrocarbon receptor (AhR) inhibitor in parallel experiments, which completely abrogated the protective effects of IAId and ILA, confirming strict dependency on AhR pathway activation. Collectively, our study identifies IAId and ILA as microbiota-derived tryptophan metabolites that regulate immune homeostasis via the gut-skin axis in a murine AD model. These findings provide experimental support for the potential of targeting these specific microbial metabolites, warranting further investigation into their therapeutic or nutritional applications for AD.
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JOURNAL OF ELECTROANALYTICAL CHEMISTRY
·
2022
·
IF 4.598
Ning Liu,Baozhu Yang,Zheng-Zhi Yin,Wenrong Cai,Junyao Li,Yong Kong
Chiral metal–organic framework (ZIF-8) was successfully prepared through a two-step electrodepostion method by using l -histidine ( l -His) as the chiral source, and the resultant chiral ZIF-8 ( l -His-ZIF-8) was used for enantiodiscrimination of the isomers of tyrosine (Tyr) and tryptophan (Trp). Although the isomers of both Tyr and Trp could be well discriminated by the l -His-ZIF-8 modified electrode, they displayed opposite voltammetric behaviors on the differential pulse voltammograms (I D-Tyr > I L-Tyr ; I D-Trp < I L-Trp ), which could be explained by density functional theory (DFT). Finally, both the pH and the electrodeposition time were optimized to obtain the highest recognition efficiency of the l -His-ZIF-8 modified electrode toward the isomers of Tyr and Trp.
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