ACTA PHARMACOLOGICA SINICA
·
2025
·
IF 8.4
Wang Hao,Xia Guo-qing,Ke Ting,Chen Xi-xi,Zhen Wen-jun,Tian Yuan-yuan,Chen Shi,Zhang Cheng,Li Jun,Zhang Lei,Wu De-jun,Wang Ye-tao,He Liang,Tian Wen-fang,Wu Bao-ming
Alcohol-related liver disease (ALD) refers to a spectrum of liver diseases caused by chronic or acute excessive alcohol consumption. Excess alcohol consumption and dysregulated immunometabolism are the major contributors to the disease progression. The pathogenesis of ALD remains unclear with macrophage activity playing a key role in disease development. Kv1.3 potassium channel is essential for the regulation of macrophage function. In this study, we investigated whether Kv1.3 channels influenced the progression of ALD by modulating macrophage function. A murine model of ALD was established in male mice. We showed that Kv1.3 knockdown significantly attenuated alcohol-induced liver injury, lipid deposition, and inflammatory responses in ALD mice. Metabolomic analysis revealed that Kv1.3 knockdown significantly increased the levels of tryptamine, a tryptophan metabolite, in the liver of ALD mice. During the last 5 days of the EtOH feeding period, injection of exogenous tryptamine (1, 10, 20 mg·kg −1 ·d −1 , i.p.) notably alleviated ethanol-induced liver steatosis and inflammation in ALD mice. In LPS-challenged RAW264.7 cells, tryptamine (62.5, 125, 250 μM) dose-dependently suppressed the secretion of pro-inflammatory cytokines IL-6, IL-1β and TNF-α. RNA-seq analysis of RAW264.7 cells revealed that tryptamine treatment significantly altered Toll-like receptor and NF-κB signaling pathways. We conclude that in the ALD mice, Kv1.3 negatively regulates tryptamine levels, which inhibits macrophage activation and reduces the inflammatory responses through the TLR4/NF-κB signaling pathway. Our results offer new targets and intervention strategies for the prevention and treatment of ALD.
研究领域:
医学
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免疫学
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代谢组学
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Zhenzhen Cai,Zhiheng Huo,Gaosheng Li,Xu Cheng,Fang Xiao,Yuwan Du,Baiyi Zu,Xincun Dou
The specific fluorescent detection of α-methyltryptamine (AMT) presents a great challenge because similar amine groups and benzene rings exist in a variety of amines. Here, we show the precise modulation of the electron-withdrawing strength of the π-conjugate bridge in aldehyde-containing Schiff base-based fluorescent probes for ultratrace AMT discrimination. It is found that different electron-withdrawing groups −C6H4, −C6H2N2, and −C6H2Br2 as the π-conjugate bridge of the 2-dicyanomethylidene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran (TCF)-based probes can classify and identify organic amines with different amine nucleophilicities. Notably, the probe with −C6H2Br2 as the π-conjugate bridge, denoted as BrFS–TCF, which has the highest electrophilicity of the recognition site, shows a superior nM-level limit of detection (LOD) and an instant response time (<0.1 s) toward AMT. Especially, it shows an excellent selectivity facing the secondary amines, tertiary amines, aromatic amines, and even primary amines. The present strategy would provide a new pathway for chemical substances with similar structures and properties and especially for fighting against illegal drugs.
研究领域:
化学
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药物分析
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生物传感
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DOI
PubMed
高影响因子
ANALYST
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2024
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IF 3.6
Yating Rui,Qunyong Tang,Liyi Chen,Juan Pu,Wangpeng Wang,Shou-Nian Ding
Baijiu, as a traditional Chinese alcoholic beverage, carries China's rich historical and cultural heritage. Consumers experience varying levels of relaxation and pleasure after consuming different Baijiu, with the biological basis of delectation influenced by serotonin and dopamine. In this study, we prepared carbon fiber electrodes modified with surface decorated gold nanoparticles to directly measure the electrochemical response signals in the serum of mice before and after gavage different types of Baijiu. It was observed that the serum signal change in mice after consuming Baijiu Sample 1 (J1) was higher than the other two types of Baijiu. Consequently, trace flavor compounds in the Baijiu samples were detected using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography mass spectrometry (LC-MS), revealing the highest content of L-lactic acid in J1. Mice were intraperitoneally injected with 200 mg/kg of L-lactic acid. The changes in dopamine and serotonin in the serum of injected mice were monitored using a biosensor, and the results were compared with results from high performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-MS). The findings confirmed that L-lactic acid could indeed stimulate both neurotransmitters' secretion in mice, suggesting that the trace components in J1 may even exhibit synergistic effects. The study contributes to a deeper under-standing of the effects of Baijiu on body and provides a scientific basis for the production and consumption of Baijiu.
研究领域:
生物化学
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神经科学
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分析化学
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DOI
PubMed
高影响因子
Biology-Basel
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2022
·Vol. 11
·期 4
·503
·
IF 5.168
Jingyun Ding,Huiyan Wang,Zequn Li,Jiangnan Sun,Peng Ding,Xiaomei Chi,Mingfang Yang,Yaqing Chang,Chong Zhao
Simple SummarySea urchins are key in the trophic cascades of benthic communities. They also possess physiological characteristics of low digestibility. Thus, we explored the relationship between the indicators (digestive enzymes activities and the gut emptying) and molecules (TRPA1 and 5-HT) related to digestive physiology in the sea urchinStrongylocentrotus intermedius. The results in the present study indicate that digestive enzyme activities and gut emptying are correlated with the TRPA1 and 5-HT in the gut ofS. intermedius.This novel finding not only is important for understanding the low food digestibility of sea urchins but provides an entry point to further investigate the molecular details of digestive physiology of sea urchins.AbstractThe energetic link in the benthic community is based on physiological characteristics of the low food absorption efficiency of sea urchins. Low food absorption efficiency of sea urchins is correlated with the activity of digestive enzymes and the duration of food in their gut. Thus, the digestive enzymes activities (pepsin and amylase enzyme activities) and gut emptying are important indicators in assessing nutrient digestion and absorption in sea urchins. In the present study, the relationship between these indicators and molecules related to digestive physiology were quantified in sea urchins. We found (1) an inter-regulatory relationship existed between Transient receptor potential cation channel, subfamily A, member 1 (TRPA1), and serotonin (5-hydroxytryptamine; 5-HT) in the gut ofStrongylocentrotus intermedius; (2) digestive enzyme activities were negatively correlated with the TRPA1 and concentration of 5-HT in the gut ofS. intermedius; (3) gut emptying rate was positively correlated with TRPA1 and concentration of 5-HT in the gut ofS. intermedius. The present study revealed that the digestion and absorption of food are correlated with the TRPA1 and 5-HT in the gut ofS. intermedius, which provides valuable information about the digestive physiology of sea urchins. This novel finding is relevant to understanding the low food digestibility of sea urchins. It also provides valuable information to the digestive physiology of sea urchins, which are key to maintaining the stability of food webs in the marine ecosystem.Keywords:sea urchin;TRPA1;5-HT;digestive enzyme;gut emptying
研究领域:
海洋生物学
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生理学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Yancheng Xie,Xue Feng,Jiaqi Tao,Qianhui Gao,Yue Li,Xinyi Liu,Mingyu Xia,Dong Wang
5-Hydroxytryptamine (5-HT) and its derivative bufotenine, which possess important physiological functions, are the primary active components in the secretions of toad parotid and skin gland. However, the biosynthetic pathway of these substances remains unclear in toads. To characterize toad's Aromatic-L-amino-acid decarboxylase (AADC), the key enzyme in the predicted 5-HT derivatives biosynthetic pathway, the full-length cDNA of AADC from Bufo bufo gargarizans ( Bbg AADC) was cloned from the parotoid gland of B. bufo gargarizans . The recombinant Bbg AADC exhibited optimal expression in E. coli BL21 (DE3) containing pCold- Bbg AADC after induction for 16 h at 15 °C with 0.3 mM IPTG, resulting in substantial yields of soluble proteins . The enzymological properties of Bbg AADC were assessed, and it was determined that the optimal reaction temperature was 37 °C, the optimal pH was 8.6, and the optimum molar ratio of pyridoxal-5′-phosphate (PLP) to Bbg AADC was found to be 3.6:1. Additionally, high substrate specificity was observed, as Bbg AADC could catalyze the production of 5-HT from 5-hydroxytryptophan (5-HTP) but not dopamine or tryptamine from levodopa or tryptophan , respectively. The Km of the recombinant protein Bbg AADC was 0.2918 mM and the maximum reaction rate (Vmax) was 1.182 μM·min −1 when 5-HTP was used as substrate. The Kcat was 0.0545 min −1 , and Kcat/Km was 0.1868 mM −1 ·min −1 . To elucidate the mechanism of Bbg AADC, molecular docking was performed with PLP and 5-HTP, or the external aldimine formed by 5-HTP and PLP. The results indicated that the active sites for Bbg AADC to bind with PLP were K303, H192, N300, A148, F309, T246, A273, and T147. W71, Y79, F80, P81, T82, H192, T246, N300, H302, F309, and R477 served as catalytically active sites for the binding of Bbg AADC to 5-HTP. Furthermore, R447, W71, S149, N300, A148, and T147 of Bbg AADC were involved in the decarboxylation reaction of the aldimine formed by PLP and 5-HTP.
研究领域:
生物化学
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分子生物学
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酶学
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DOI
PubMed
高影响因子
Chinese Medicine
·
2024
·Vol. 19
·期 1
·1-18
·
IF 5.3
Zhen Jianhua,Li Yini,Zhang Yunan,Zhou Yali,Zhao Lu,Huang Guangrui,Xu Anlong
Background Shaoyao Decoction (SYD) is a widely recognized herbal formula utilized in traditional Chinese medicine for the treatment of diarrhea. Although it has demonstrated significant effectiveness in clinical practice for treating ulcerative colitis, the precise mechanisms by which it operates remain largely elusive. Methods The active ingredients of SYD were obtained by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), which were used to explore the potential pharmacological mechanism based on TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) and PANTHER (Protein Analysis Through Evolutionary Relationships) classification system. In a mouse model of dextran sulfate sodium (DSS)-induced colitis, mRNA sequencing, 16S rDNA sequencing and targeted metabolomics techniques were used to elucidate the mechanisms of SYD, and immunohistochemistry, immunofluorescence, enzyme linked immunosorbent assay, real time quantitative polymerase chain reaction and western blot were used to test the key targets. In addition, QGP-1 and H9 cells were performed to validate the discoveries from the animal experiments. Results In the mouse model of DSS-induced colitis, SYD effectively alleviated symptoms such as bloody stool, tissue damage, inflammation, intestinal flora dysbiosis and abnormal gene expression. Analyses of both differential expressed genes in colonic tissue and predicted 16S rDNA genes, as well as the analyses of targeted genes from TCMSP based on the active ingredients in UPLC-MS/MS of SYD, uncovered the enrichment of pathways involved in the biosynthesis and degredation of 5-hydroxytryptamine (5-HT). Interestingly, SYD suppressed the relative abundance of key genes in 5-HT synthesis, Tph1(Tryptophan hydroxylase 1) and Ddc (Dopa decarboxylase), in faeces from DSS-induced mice, leading to a reduction in the concentration of fecal 5-HT. Moreover, SYD augmented the production of butyric acid. Subsequently, increasing butyric acid influenced the metabolism of 5-HT in the organism through G protein-coupled receptor 43 by impeding its synthesis, facilitating its transport and degredation. These findings were additionally corroborated in a model utilizing enterochromaffin cell (QGP-1 cells). Furthermore, reduced levels of 5-HT hindered the activation of T lymphocytes (H9 cells) via the PKC (Protein kinase C) and NF-κB (Nuclear factor kappa-B) signaling pathways, by means of HTR1A (5-HT receptor 1A) and HTR3 (5-HT receptor 3). Additionally, diminished secretion of 5-HT resulted in reduced secretion of associated cytokines, thereby alleviating inflammation in the colon. Conclusion Through modulation of T lymphocyte activation mediated by 5-HT metabolism in the local colon via the intestinal flora and its metabolite, SYD effectively mitigated colonic inflammation in DSS-induced mice.
研究领域:
药理学
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免疫学
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胃肠病学
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微生物学
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代谢组学
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DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2023
·
IF 8.4
Lin Pang,Tianshi Zhang,Yuan Liu,Dezhong Li,Jiguang Li,Ming Guan,Xincun Dou
Tryptamines , an important family of new psychoactive substances, have attracted special attention from the international community owing to their abuse and corresponding influence on human health and social stabilization. However, realizing the on-site analysis of tryptamines with rapid and precise responses remains a great challenge, especially if these are present in their disguised form. A highly sensitive and specific analytical method was developed herein, driven by a dual noncovalent interaction towards tryptamines. An optical probe was designed to specifically recognize tryptamines via π–π stacking and hydrogen bond effect to produce significant optical responses for both colorimetric and fluorescent modes. The detection limits were calculated as 4.1 nM (fluorescent mode) and 17.2 μM (colorimetric mode), respectively, with an excellent specificity towards 16 interfering substances within 0.6 s. Based on the excellent detection performances of the proposed probe, a portable and operable sensor was developed and demonstrated with the rapid and accurate analysis capability towards the controlled α -methyl-tryptamine in complicated scenarios. We expect the portable sensor equipped with this optical probe would provide a powerful tool for trace tryptamine detection and effective technical support for real-time monitoring of other new psychoactive substances in complicated media.
研究领域:
分析化学
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药物分析
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生物医学工程
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DOI
高影响因子
Desalination and Water Treatment
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2024
·
IF 1
Jiaming Hu,Shuai Zhang,Chen Feng,Shanggeng Li,Longfei Zhang,Jiajun Ma,Qiang Yin
In this work, an efficient Fe 3+ adsorbent was synthesized by using the tryptamine and sodium carboxymethyl cellulose (CMC-Na) modified polyacrylamide gel. The functional monomers synthesized by the reaction of tryptamine and methacrylic acid chloride were doped into the composition, and CMC-Na participated in the formation of the gel network. By changing different conditions, the optimal use conditions of the gel were explored. The Langmuir and Freundlich isotherm models were used to discuss the adsorption behavior. According to the fitting results, the Freundlich model was more suitable for explaining the adsorption of Fe 3+ by gels. The feasibility of its adsorption process was confirmed by the study of its kinetics and thermodynamics. As an adsorbent, tryptamine CMC-Na modified polyacrylamide gel has excellent ability to remove Fe 3+ from aqueous solutions. The maximum adsorption capacity of tryptamine and CMC-Na modified polyacrylamide gel for Fe 3+ reached 127.5 mg g −1 .
研究领域:
环境科学
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材料科学
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化学工程
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DOI
高影响因子
MOLECULES
·
2020
·Vol. 25
·期 20
·4702
·
IF 3.267
Nan Zhang,Mu Luo,Lei He,Lei Yao
Gardenia jasminoidesEllis is a famous fragrant flower in China. Previous pharmacological research mainly focuses on its fruit. In this study, the essential oil of the flower of ‘Shanzhizi’, which was a major variety for traditional Chinese medicine use, was extracted by hydro distillation and analyzed by GC-MS. Mouse anxiety models included open field, elevated plus maze (EPM), and light and dark box (LDB), which were used to evaluate its anxiolytic effect via inhalation. The involvement of monoamine system was studied by pretreatment with neurotransmitter receptor antagonists WAY100635, flumazenil and sulpiride. The monoamine neurotransmitters contents in the prefrontal cortex (PFC) and hippocampus after aroma inhalation were also analyzed. The results showed that inhalation ofG. jasminoidesessential oil could significantly elevated the time and entries into open arms in EPM tests and the time explored in the light chamber in LDB tests with no sedative effect. WAY100635 and sulpiride, but not flumazenil, blocked its anxiolytic effect. Inhalation ofG. jasminoidesessential oil significantly down-regulated the 5-HIAA/5-HT in the PFC and reduced the 5-HIAA content in hippocampus compared to the control treatment. In conclusion, inhalation of gardenia essential oil showed an anxiolytic effect in mice. Monoamine, especially the serotonergic system, was involved in its anxiolytic effect.Keywords:Gardenia jasminoides;essential oil;inhalation;anxiolytic effect;serotonergic neurotransmission
研究领域:
药理学
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神经科学
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植物化学
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DOI
PubMed
高影响因子
TALANTA
·
2022
·
IF 6.556
Hao Feng,Fan Wang,Junhua Li,Qian Wu,Ying Cui,Lingzhi He,Xing Liu,Zeng Liu,Dong Qian,Haixia Tong
Lack of highly efficient, inexpensive, and easily available catalysts severely limits the practical applicability of electrochemically sensing assay towards 5-hydroxytryptamine (5-HT). Herein, four kinds of Fe–Co bimetallic Prussian blue analogues (FeCo–PBAs) with different molar ratios of Fe to Co were prepared using a simple coprecipitation method. Interestingly, Fe(III) in K 3 [Fe(CN) 6 ] can be reduced to Fe(II) by adding trisodium citrate dehydrate, which could offer a new clue to synthesize PBAs with Fe(II) core ions. With the optimizational FeCo-PBA synthesized at a 0.5/1 M ratio of Fe to Co as an electrocatalyst , the constructed sensor shows excellent comprehensive performance for the 5-HT assay with a high sensitivity of 0.856 μA μM −1 and an ultralow detection limit of 8.4 nM. Under the optimum conditions, linearity was obtained in the ranges of 0.1–10.0 μM and 10.0–200.0 μM and preferable recoveries ranged from 97.8% to 103.0% with relative standard deviation (RSD) < 4.0%. The integrated properties of FeCo-PBA can be comparable to previously reported electrocatalysts for the 5-HT assay including noble metal-based and expensive carbon (graphene and carbon nanotubes)-based electrocatalysts. The proposed sensor also exhibits outstanding selectivity, reproducibility, and practicality for real sample analyses. This work is the first report on the PBA-based sensor for the 5-HT assay, verifying the practicability of this high-performance sensor for the 5-HT assay.
研究领域:
生物化学
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分析化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF LEUKOCYTE BIOLOGY
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2024
·
IF 3.6
Sun Yilu,Chen Qilei,Cui Wei,Chen Hubiao,Zhao Jia,Rong Jianhui
Dysregulation of brain innate immunity involving microglia is implicated in the pathology of neurological disorders including depression. Depression is a prominent medical challenge to global public health systems. Synthetic antidepressant drugs are limited by severe side-effects. The present study aimed to identify the active compounds from the well-documented herbal medicine formula Banxia-Houpo decoction (BHD) and discover the underlying mechanisms for tuning microglia. We initially employed LC-MS profiling and network pharmacology analysis to predict the active compound-target interaction networks. We subsequently validated the potential active compounds and targets in a mouse model of corticosterone (CORT)-induced depression and post-synaptic microglia BV2 cells. As results, 64 compounds were identified in the ethanolic BHD extract and predicted to target 25 depression-related genes. Interestingly, the serotonergic synapse pathway received the highest enrichment score while 5-hydroxytryptamine receptor 1A (HTR1A) was targeted by six compounds (i.e., baicalein, luteolin, N-nornuciferine, roemerine, scutellarin, 6-shogaol). In parallel assays, a six-compound combo (SCC) and BHD markedly ameliorated the depressive-like behaviors in CORT-lesioned mice and well protected highly differentiated (HD) PC12 cells against CORT challenge. Moreover, SCC and BHD effectively induced HTR1A expression in mice and post-synaptic microglia BV2 cells. HTR1A antagonist WAY-100635 at 1mg/kg/d via intraperitoneal injection attenuated the effects of SCC and BHD on the depressive behaviors in mice. These results suggest that SCC might be a potential remedy against depression and other neurological disorders via targeting HTR1A in microglia.
研究领域:
药理学
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神经科学
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分子生物学
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行为科学
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DOI
PubMed
高影响因子
NUCLEAR MEDICINE AND BIOLOGY
·
2024
·
IF 3.6
Yuli Sun,Guangwen Li,Haiyan Hong,Lin Zhu,Hank F. Kung,Yan Zhang,Jinxia Zhu
Objective Diabetes mellitus (DM) is one of the major diseases in the world. Nuclear medicine imaging may be able to detect functional status of pancreatic β cells in vivo , which might elucidate the pathological mechanisms of diabetes and develop individualized treatment plans. In this study, we evaluated the ability of [ 125 I]ADAM, a serotonin transporter (SERT) imaging agent, as a probe for detecting pancreatic β-cell mass (BCM). Methods In vitro cell studies were evaluated in INS-1 cells (rat islet β cell line). Biodistribution studies were performed in male normal Sprague-Dawley rats and alloxan-induced type 1 diabetes mellitus (T1DM) rats. Distribution and expression of SERT protein in pancreas of rats were also measured by immunofluorescence staining and Western blot. Results In vitro cell studies showed that the concentration of [ 125 I]ADAM associated with the INS-1 cells was increased gradually with incubation time, and the SERT specific inhibitor, escitalopram, exhibited the inhibitory effect on this interaction. Biodistribution studies also showed that the uptake of [ 125 I]ADAM in the pancreas of normal rats was decreased in the presence of escitalopram. However, in the T1DM rat model with a significant β cells reduction, the uptake of pancreas was increased when compared with the control. Through immunofluorescence staining and Western blot, it was found that both the endocrine and exocrine cells of the normal pancreas expressed SERT protein, and the level of SERT protein in the exocrine cells was higher than islets. In the diabetic state, the expression of SERT in the exocrine cells was further increased. Conclusions The SERT imaging agent, [ 125 I]ADAM, at the present form will not be suitable for imaging β cells, specifically because there were extraordinarily high non-specific signals contributing from the exocrine cells of pancreas. In addition, we noticed that the level of SERT expression was abnormally elevated in the diabetic state, which might provide an unexpected target for studying the pathological mechanisms of diabetes.
研究领域:
医学影像学
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内分泌学
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糖尿病研究
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DOI
高影响因子
危险品化学品经营许可证（带存储）