INFLAMMATION
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2021
·Vol. 44
·期 5
·2018-2032
·
IF 4.092
Zhou Changkai,Gao Jing,Ji Hongyan,Li Wenjing,Xing Xiaomin,Liu Donghua,Guo Qie,Zhou Lihua,Jing Fanbo
Previous studies have shown that benzoylaconine (BAC), a representative monoester alkaloid, has a potential anti-inflammatory effect. This study investigated the underlying molecular mechanisms using the mode of LPS-activated RAW264.7 macrophage cells. Our findings showed that BAC significantly suppressed the release of pro-inflammatory cytokines and mediators, including IL-6, TNF-α, IL-1β, ROS, NO, and PGE 2 . BAC treatment also effectively downregulated the elevated protein levels of iNOS and COX-2 induced by LPS in a dose-dependent manner. In this study, we found that BAC inhibited LPS-induced NF-κB activation by reducing the phosphorylation and degradation of IκBα by western blotting and blocking the nuclear translocation of p65 using an immunofluorescence assay. The elevated protein levels of JNK, p38, and ERK phosphorylation after LPS stimulation were restored effectively by BAC treatment. The protein expression of Toll-like receptor 4 (TLR4) and LPS-induced phosphorylation of TAK1, which is a crucial upstream regulatory factor of TLR-induced MAPK and NF-κB signaling, were inhibited by BAC in activated RAW264.7 macrophages. Moreover, BAC decreased the levels of TAK1 phosphorylation and pro-inflammatory cytokines and mediators associated with MAPK and NF-κB activation, similar to TLR4 inhibitor TAK-242. These findings demonstrated that BAC exhibited an anti-inflammatory effect by the inhibition of TLR-induced MAPK and NF-κB pathways, indicating that it could potentially be used for treating inflammatory diseases.
研究领域:
免疫学
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药理学
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细胞生物学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Falan Li,Xinyue Ye,Mingwei Li,Qin Nie,Huihui Wang,Guoqing Zhang,Liyun Dong,Caifen Wang,Li Wu,Hongfei Liu,Lifeng Wang,Can Peng,Jiwen Zhang
Atropine sulfate (ATS) eye drops at low concentrations constitute a limited selection for myopia treatment, with challenges such as low ophthalmic bioavailability and inadequate stability. This study proposes a novel strategy by synthesizing ophthalmic sodium polystyrene sulfonate resin (SPSR) characterized by a spherical shape and uniform size for cationic exchange with ATS. The formulation of ATS@SPSR suspension eye drops incorporates xanthan gum and hydroxypropyl methylcellulose (HPMC) as suspending agents. In vitro studies demonstrated that ATS@SPSR suspension eye drops exhibited sustained release characteristics, and tropic acid, its degradation product, remained undetected for 30 days at 40 °C. The ATS levels in the tear fluids and aqueous humor of New Zealand rabbits indicated a significant increase in mean residence time (MRT) and area under the drug concentration–time curve (AUC 0-12 h ) for ATS@SPSR suspension eye drops compared to conventional ATS eye drops. Moreover, safety assessment confirmed the non-irritating nature of ATS@SPSR suspension eye drops in rabbit eyes. In conclusion, the cation-responsive sustained-release ATS@SPSR suspension eye drops enhanced the bioavailability and stability of ATS, offering a promising avenue for myopia treatment.
研究领域:
药学
·
眼科
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2025
·
IF 3.1
Lin Chen,Han Huang,Xiali Liu,Peijing Zhao,Biao Zhou
A novel oxyphenisatin analogue was identified in a type of jelly candy during routine inspections of food products marketed for weight-loss purposes. Through analysis utilizing ultra-high-performance quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS), the fragment ions at m/z 258 and 195 observed in the MS/MS experiments were found to be consistent with those of 4-Chloro-oxyphenisatin diacetate. It was inferred that the unknown compound is likely a derivative of 4-Chloro-oxyphenisatin diacetate. The candy was separated and purified by column chromatography, and the purified compound was determined to be 96.4 % by high-performance liquid chromatography (HPLC). Subsequently, the structure was confirmed through nuclear magnetic resonance (NMR) spectroscopy. Based on the data, it was concluded that the structure of the unknown compound involved the substitution of two symmetrical acetyl groups in the 4-chloro-oxyphenisatin diacetate molecule with two isobutyl groups. Ultimately, the novel oxyphenisatin analogue was identified as (5-chloro-2-oxoindolin-3,3-ylidene) bis (4,1-phenylbutan-2-yl) diisobutyrate and designated as 4-Chloro-oxyphenisatin diisobutyrate. Finally, a quantitative analysis of the novel unknown compound in the jelly candy revealed a concentration of 6 mg per pellet. Based on the recommended daily consumption of one pellet, as indicated on the product packaging, the level of illegal additives may lead to diarrhoea and consequently poses a risk to human health. To the best of our knowledge, this represents the first report on the identification of 4-Chloro-oxyphenisatin diisobutyrate.
研究领域:
药物化学
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食品安全
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分析化学
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2015
·
IF 4.097
Amin Zhang,Chongchong Miao,Hongyuan Shi,Hongkun Xiang,Chusen Huang,Nengqin Jia
Recent years have witnessed the great development of electrochemiluminescence (ECL) as a platform for the analytical processes in many fields, which includes pharmaceutical analysis, immunoassay, DNA analysis as well as clinical analysis. Herein, a novel electrochemiluminescence (ECL) sensor was fabricated for ultrasensitive detection of atropine based on Ru(bpy) 3 2+ /carbon nanospheres/Nafion composite film. The carbon nanospheres (CNPs) in composite film were obtained through a hydrothermal method. Then, electrochemical and ECL behaviors of the proposed sensor were investigated. Under the optimal conditions, the constructed atropine sensor showed a wide linear range from 0.5 to 250 μM with a detection limit of 0.17 μM (at signal-to-noise ratio of 3). Moreover, the results indicated that the CNPs-based ECL sensor exhibited excellent sensitivity and favorable stability, which might be ascribed to the high surface area and the good electrical conductivity of CNPs. Furthermore, the ECL sensor was applied for the determination of atropine in atropine sulfate injection samples and displayed a desirable result. The proposed ECL sensor could be easily obtained and be promising used for drug assay.
研究领域:
分析化学
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药学
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电化学
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纳米技术
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产品关联
DOI
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2020
·
IF 6.551
Kun Qiao,Tiantian Hu,Yao Jiang,Jianping Huang,Jingjin Hu,Wenjun Gui,Qingfu Ye,Shuying Li,Guonian Zhu
Chlorpyrifos is a widely used organophosphate insecticide and ubiquitously detected in the environment. However, little attention has been paid to its endocrine disrupting effect to non-target organisms. In the present study, zebrafish was exposed to 13 and 65 μg/L of chlorpyrifos for 7 and 10 days to determine the induced neurotoxicity and the alteration of thyroid metabolism. The 120 h LC 50 and LC 10 of chlorpyrifos was estimated as 1.35 mg/L and 0.62 mg/L based on the acute embryo toxicity assay, respectively. The acetylcholinesterase (AChE) inhibitory was detected by 13 μg/L chlorpyrifos and could be reversed by the co-exposure of 100 and 1000 μg/L anticholinergic agent atropine. For thyroid hormone level, 13 and 65 μg/L of chlorpyrifos induced increased free T 3 levels in 10 dpf (days post-fertilization). The expression of thyroid related genes in 7 and 10 dpf exposed zebrafish were measured by the quantitative Real-Time PCR (qRT-PCR) assay. The mRNA expression of tshba , thrb , crhb , ttr , tpo , ugt1ab and slc5a5 had significant change. However, the alterations of thyroid hormone and mRNA expression could be partly rescued by the addition of atropine. The molecular docking of chlorpyrifos and T 3 to the thyroid receptor β in zebrafish using homology modelling and CDOCKER procedures shown weaker binding ability of chlorpyrifos compared to T 3 . Therefore, we concluded that the disturbance of thyroid signaling in zebrafish might arise from the developmental neurotoxicity induced by chlorpyrifos.
研究领域:
环境毒理学
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内分泌学
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分子生物学
·
水生毒理学
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DOI
PubMed
高影响因子
WORLD JOURNAL OF GASTROENTEROLOGY
·
2012
·
IF 2.471
Da-Peng Chen,Yong-Jian Xiong,Ze-Yao Tang,Qi-Ying Yao,Dong-Mei Ye,Sha-Sha Liu,Yuan Lin
AIM: To characterize the dual effects of deslanoside on the contractility of jejunal smooth muscle. METHODS: Eight pairs of different low and high contractile states of isolated jejunal smooth muscle fragment (JSMF) were established. Contractile amplitude of JSMF in different low and high contractile states was selected to determine the effects of deslanoside, and Western blotting analysis was performed to measure the effects of deslanoside on myosin phosphorylation of jejunal smooth muscle. RESULTS: Stimulatory effects on the contractility of JSMF were induced (45.3% ± 4.0% vs 87.0% ± 7.8%, P < 0.01) by deslanoside in 8 low contractile states, and inhibitory effects were induced (180.6% ± 17.8% vs 109.9% ± 10.8%, P < 0.01) on the contractility of JSMF in 8 high contractile states. The effect of deslanoside on the phosphorylation of myosin light chain of JSMF in low (78.1% ± 4.1% vs 96.0% ± 8.1%, P < 0.01) and high contractile state (139.2% ± 8.5% vs 105.5 ± 7.34, P < 0.01) was also bidirectional. Bidirectional regulation (BR) was abolished in the presence of tetrodotoxin. Deslanoside did not affect jejunal contractility pretreated with the Ca 2+ channel blocker verapamil or in a Ca 2+ -free assay condition. The stimulatory effect of deslanoside on JSMF in a low contractile state (low Ca 2+ induced) was abolished by atropine. The inhibitory effect of deslanoside on jejunal contractility in a high contractile state (high Ca 2+ induced) was blocked by phentolamine, propranolol and L-NG-nitro-arginine, respectively. CONCLUSION: Deslanoside-induced BR is Ca 2+ dependent and is related to cholinergic and adrenergic systems when JSMF is in low or high contractile states.
研究领域:
药理学
·
胃肠生理学
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DOI
PubMed
高影响因子
FORENSIC SCIENCE INTERNATIONAL
·
2013
·
IF 2.307
Liang Meng,Pinjia Meng,Bugang Tang,Qingqing Zhang,Yanji Wang
Based on molecularly imprinted photonic hydrogels (MIPHs) that combined the colloidal-crystal with molecular imprinting technique, a novel label-free colorimetric chemosensor for convenient and fast efficient detection of atropine with high sensitivity and specificity was developed. Due to the special inverse opal arrays with a thin polymer wall in which the imprinted nanocavities of atropine moleculars distributed, the proposed MIPHs designed as water-compatible exhibited high sensitive (as low as 1 pg/mL), rapid responsive (less than 30 s) and specific detection of atropine in complex matrix. The unique three-dimensional, highly-ordered photonic hydrogels would be obviously swelling in response to the specific atropine molecular recognition process and the response would be directly transferred into visually perceptible optical signal (change in color) that could be detected by the naked eye through Bragg diffractive shifts of ordered macroporous arrays. With a broad concentration range varying from 1 pg/mL to 1 μg/mL of atropine, the distinct color changes of MIPHs almost covered the whole visible-light wavelength range from blue to red for semi-quantitative analysis. The smart chemosensor was successfully employed to determine the trace level atropine in human urine samples, providing a fast and effective alternative for semi-quantitative detection of atropine for clinical analysis and forensic investigations.
研究领域:
分析化学
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生物传感器
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材料科学
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临床分析
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法医学
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产品关联
DOI
PubMed
高影响因子
FITOTERAPIA
·
2014
·
IF 2.216
Yong-Jian Xiong,Da-Peng Chen,Bo-Chao Lv,Fang-Fei Liu,Li Wang,Yuan Lin
Nobiletin , a citrus polymethoxylated flavone , exhibits multiple biological properties including anti-inflammatory, anti-carcinogenic, and anti-insulin resistance effects. The present study found that nobiletin exerted significant stimulatory effects on the contractility of isolated rat jejunal segments in all 6 different low contractile states, and meanwhile significant inhibitory effects in all 6 different high contractile states, showing characteristics of bidirectional regulation (BR). Nobiletin-exerted BR on jejunal contractility was abolished in the presence of c-kit receptor tyrosine kinase inhibitor imatinib or Ca 2 + channel blocker verapamil . In the presence of neuroxin tetrodotoxin , nobiletin only exerted stimulatory effects on jejunal contractility in both low and high contractile states. Hemicholinium-3 and atropine partially blocked nobiletin-exerted stimulatory effects on jejunal contractility in low-Ca 2 + -induced low contractile state. Phentolamine or propranolol or l -NG-nitro-arginine significantly blocked nobiletin-exerted inhibitory effects on jejunal contractility in high-Ca 2 + -induced high contractile state respectively. The effects of nobiletin on myosin light chain kinase (MLCK) mRNA expression, MLCK protein content, and myosin light chain phosphorylation extent were also bidirectional. In summary, nobiletin-exerted BR depends on the contractile states of rat jejunal segments. Nobiletin-exerted BR requires the enteric nervous system, interstitial cell of Cajal, Ca 2 + , and myosin phosphorylation-related mechanisms.
研究领域:
药理学
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胃肠病学
·
分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2022
·
IF 3.571
Chen Wang,Dongyang Zhu,Jian Zhang,Yingxiang Du
Metal organic frameworks (MOFs), as a novel separation medium s , have in recent years attracted wide consideration in capillary electrochromatography (CEC). However, the instability of frameworks limited the application of the MOF-based chiral separation capillary. Herein, Iron-based γ-cyclodextrin metal-organic framework (Fe-CD-MOF) with mesoporous was developed as the chiral stationary phase in open tubular capillary electrochromatography column (OT-CEC) for the stereoisomer separation of fourteen chiral drugs and one chiral alcohol. The capillary column with MOF coating exhibited the best performance (resolution value: 17.07) for anisodamine in any MOF-based capillary column that has never been reported. Moreover, the effect of pH, buffer concentration, and methanol content has been investigated. The novel coated capillary was also applied for the quantitative analysis of a real sample. The Fe-CD-MOF coated capillary showed outstanding repeatability and stability, with the satisfactory relative standard deviations (RSDs) for intra-day, inter-day, and column-to-column. Finally, the enantioseparation mechanism of the Fe-CD-MOF coated capillary was evaluated by adsorption kinetic experiments. In summary, this work indicated the novel and renewable Fe-CD-MOF was a potential chiral stationary phase in CEC chiral separation.
研究领域:
分析化学
·
色谱学
·
材料科学
·
药物分析
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2013
·Vol. 65
·期 5
·734-744
·
IF 2.033
Chen Da-Peng,Xiong Yong-Jian,Lv Bo-Chao,Liu Fang-Fei,Wang Li,Tang Ze-Yao,Lin Yuan
ObjectivesThe aim of the study was to evaluate berberine-induced bidirectional regulation on the contractility of jejunum.MethodsDifferent low and high contractile states of isolated jejunal segment from rat were established to investigate the effects of berberine.Key findingsStimulatory effects on jejunal segment were exerted by berberine in six low contractile states and inhibitory effects were produced on jejunal segment in six high contractile states. The effects of berberine on myosin light chain kinase (MLCK) mRNA expression, MLCK protein content, and myosin phosphorylation in jejunum were also bidirectional. Bidirectional regulation was not observed in the presence of tetrodotoxin. No regulatory effects of berberine on jejunal contractility were observed in the presence of verapamil. The stimulatory effects of berberine on jejunal contractility were blocked by atropine. The inhibitory effects of berberine on jejunal contractility were abolished by phentolamine, propranolol and L-NG-nitro-arginine, respectively.ConclusionsBerberine-induced bidirectional regulation needed the presence of the enteric nervous system, and depended on the influx of extracellular Ca2+, related to the cholinergic system while jejunum was in low contractile states, and related to the adrenergic system and nitric oxide relaxing mechanism while jejunum was in high contractile states. The results suggested the potential clinical implication of berberine for alternating-type irritable bowel syndrome.
研究领域:
药理学
·
胃肠病学
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神经科学
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DOI
PubMed
高影响因子
iMeta
·
2025
·
IF 33.2
Cunzheng Zhang,Yuzhu Chen,Ruqiao Duan,Yiming Zhang,Haonan Zheng,Jindong Zhang,Tao Zhang,Jingxian Xu,Kailong Li,Fei Pei,Liping Duan
Maternal health, specifically changes in the gut microbiota, can profoundly impact offspring health; however, our understanding of how gut microbiota alterations during the preconception period influence the offspring remains limited. In this study, we investigated the impact and mechanisms of preconception maternal gut dysbiosis on the development of the enteric nervous system (ENS) in mice. We found that preconception maternal exposure to antibiotics led to the abnormal development of the ENS in offspring, increasing their susceptibility to water avoidance stress at the adult stage. Metagenomic, targeted metabolomic, and transcriptomic analyses revealed that preconception antibiotic exposure disrupted the expression of genes crucial for embryonic ENS development by altering maternal gut microbiota composition. Multi-omics analysis combined with Limosilactobacillus reuteri and propionate gestational supplementation demonstrated that the maternal gut microbiota and metabolites may influence embryonic ENS development via the GPR41–GDNF/RET/SOX10 signaling pathway. Our findings highlight the critical importance of maintaining a healthy maternal gut microbiota before conception to support normal ENS development in offspring. Graphical Preconception administration of antibiotics to female mice reduces the abundance of Limosilactobacillus reuteri in the maternal gut microbiota during pregnancy, subsequently affecting propionate levels. Decreased propionate levels downregulated the expression of Gdnf / Ret / Sox10 mediated by GPR41, leading to abnormal development of the enteric nervous system during the embryonic period. This dysplasia results in colonic dysmotility, impaired colonic epithelium, and increased susceptibility to water-avoidance stress in offspring. Highlights Preconception maternal antibiotic exposure results in the abnormal development of the enteric nervous system (ENS) and intestinal mucosa in mouse offspring, thereby increasing their susceptibility to water avoidance stress in adulthood. Preconception maternal antibiotic exposure alters the composition of the maternal gut microbiota, leading to abnormal embryonic ENS development via the modulation of gene expression. Multi-omics analysis and supplementation with Limosilactobacillus reuteri and propionate during pregnancy indicate that the maternal gut microbiota and metabolites affect embryonic ENS development through the GPR41–GDNF/RET/SOX10 signaling pathway.
研究领域:
微生物学
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发育生物学
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神经科学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
BMC Chemistry
·
2024
·Vol. 18
·期 1
·1-15
·
IF 4.3
Huang Xiaomin,Wang Ting,Wang Ludan,Sun Yantao,Zhang Ziru,Zhang Yajun
In the investigation of active ingredients from natural products, current technologies relying on drug–target affinity recognition analysis face significant challenges. This is primarily due to their limited specificity and inability to provide downstream pharmacodynamic information, such as agonistic or antagonistic activity. In this study, a two-point method was developed by immobilizing M3 acetylcholine receptor (M3R) through the combination of the conformation-specific peptide BJ-PRO-13a and the HaloTag trap system. We systematically assessed the specificity of the immobilized M3R using known M3R antagonists (pirenzepine and atropine) and agonists (cevimeline and pilocarpine). By frontal analysis and nonlinear chromatography, the performance of immobilized M3R was evaluated in terms of binding kinetics and thermodynamics of four drugs to the immobilized M3R. Additionally, we successfully identified two M3R antagonists within an extract from Daturae Flos (DF), specifically hyoscyamine and scopolamine. Our findings demonstrate that this immobilization method effectively captures receptor-ligand binding interactions and can discern receptor agonists from antagonists. This innovation enhances the efficiency of receptor chromatography to determine binding-affinity in the development of new drugs, offering promise for the screening and characterization of active compounds, particularly within complex natural products.
研究领域:
药理学
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分析化学
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天然产物研究
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）