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This study aimed to explore the pharmacodynamics and mechanisms of different processing methods of Ligustrum lucidum Ait. (LLA) in addressing kidney-yin deficiency (KYD). Forty-eight Sprague-Dawley rats were divided into eight groups based on their weight. The KYD model was established by intragastric administration of levothyroxine sodium. Each group was administered the corresponding treatment for 15 consecutive days. The general condition of the rats during the treatment period was observed. In addition, the levels of cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), and the ratio of cAMP to cGMP in the serum of rats from different groups were measured. Serum samples were analyzed using the ultra-performance liquid chromatography (UPLC)-Orbitrap Fusion MS technique for metabolomics analysis. Compared with the model group, the general condition of the rats in the wine-steamed L. lucidum group (WL) and salt-steamed L. lucidum group (SSL) groups showed significant improvement. The serum levels of cAMP, cGMP, and the cAMP-to-cGMP ratio tended to return to normal. Metabolic analysis identified 38 relevant biomarkers and revealed 3 major metabolic pathways: phenylalanine, tyrosine, and tryptophan biosynthesis; phenylalanine metabolism; and sphingolipid metabolism. The different processing methods of LLA demonstrated therapeutic effects on KYD in rats, likely related to the restoration of disturbed metabolism by adjusting the levels of endogenous metabolites in the kidney. The SSL demonstrated significantly superior effects compared with the other four types of LLA processed products.
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A photoexcited sulfenylation of C(sp3)-H bonds in amides is developed for the synthesis of sulfenyl amides using thiosulfonates as a sulfur source. In the presence of easily available and inexpensive Na2-eosin Y, TBHP and K2CO3, various sulfenyl amides can be obtained under the irradiation of blue light at room temperature.
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Amidas , Enxofre , Amidas/química , Enxofre/químicaRESUMO
A general visible-light-promoted metal-free synthesis of secondary and tertiary thiocarbamates starting from thiosulfonates and N-substituted formamides is developed. By employing rhodamine B as a photocatalyst and tert-butyl hydroperoxide (TBHP) as an oxidant, a wide scope of thiocarbamates can be obtained through direct thiolation of acyl C-H bonds under irradiation of blue light at room temperature for 12 h.
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Rhubarb, a famous traditional Chinese medicine, shows a wide range of physiological activities and pharmacological benefits. Rhubarb anthraquinones are perceived as the pharmacologically active compounds of Rhubarb, and understanding metabolism of them is crucial to assure safety and effectiveness of clinical application. In this study, the pharmacokinetics, tissue distribution and excretion of five rhubarb anthraquinones (aloe-emodin, rhein, emodin, chrysophanol, physcion) were systematically investigated after oral administration of rhubarb extract to rats.An HPLC method was developed and validated for quantitation of five rhubarb anthraquinones in rat plasma, tissues, urine and faeces to investigate the Pharmacokinetic characteristics. The results showed that the proposed method was suitable for the quantification of five anthraquinones in plasma, tissue and excreta samples with satisfactory linear (r > 0.99), precision (<10%) and recovery (85.12-104.20%). The plasma concentration profiles showed a quick absorption with the mean Tmax of 0.42-0.75 h and t1/2 of 6.60-15.11 h for five anthraquinones. The analytes were widely distributed in most of the tissues. Approximately 0.13-10.59% and 28.47-81.14% of five anthraquinones were recovered in urine and faeces within 132 h post-dosing, which indicated the major elimination route was faeces excretion.In summary, this study lays a foundation for elucidating the pharmacokinetic rule of rhubarb anthraquinone and the important data can provide reliable scientific resource for further research.
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Rheum , Administração Oral , Animais , Antraquinonas , Cromatografia Líquida de Alta Pressão , Ratos , Ratos Sprague-Dawley , Distribuição TecidualRESUMO
To establish high performance liquid chromatography(HPLC) fingerprints for crude and processed Ligustri Lucidi Fructus,and to evaluate their quality through the similarity calculation and chemical pattern recognition. The separation was performed with Syncronis C_(18) column(4.6 mm × 250 mm, 5 µm), with acetonitrile(A) and 0.1% phosphoric acid solution(B) as the mobile phase for gradient elution, and a detection wavelength of 280 nm. HPLC was used to detect 22 batches of crude and processed Ligustri Lucidi Fructus,and the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 Edition) was used to evaluate the similarity among 22 batches. The research on pattern recognition was conducted with cluster analysis(CA), principal component analysis(PCA), and partial least squares discriminate analysis(PLS-DA). HPLC fingerprints of crude and processed Ligustri Lucidi Fructus were established, with similarity ranging from 0.9 to 1.0. The crude and processed Ligustri Lucidi Fructus can be obviously distinguished by using CA, PCA and PLS-DA. According to the results of PLS-DA,11 constituents including hydroxytyrosol, tyrosol, specnuezhenide and oleuropein were the main marker components leading to the difference. The established fingerprint method is stable and reliable, and can provide method basis for quality control of crude and processed Ligustri Lucidi Fructus. Chemical pattern recognition is proved to be helpful in comprehensive quality control and evaluation of Ligustri Lucidi Fructus before and after the process.
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Medicamentos de Ervas Chinesas , Ligustrum , Cromatografia Líquida de Alta Pressão , Frutas , Medicina Tradicional ChinesaRESUMO
(1) Background: Rhubarb anthraquinones-a class of components with neuroprotective function-can be used to alleviate cerebral ischemia reperfusion injury. (2) Methods: The three pharmacodynamic indicators are neurological function score, brain water content, and cerebral infarction area; UPLC-MS/MS was used in pharmacokinetic studies to detect plasma concentrations at different time points, and DAS software was used to calculate pharmacokinetic parameters in a noncompartmental model. (3) Results: The results showed that the pharmacodynamics and pharmacokinetics of one of the five anthraquinone aglycones could be modified by the other four anthraquinones, and the degree of interaction between different anthraquinones was different. The chrysophanol group showed the greatest reduction in pharmacodynamic indicators comparing with other four groups where the rats were administered one of the five anthraquinones, and there was no significant difference between the nimodipine group. While the Aloe-emodin + Physcion group showed the most obvious anti-ischemic effect among the groups where the subjects were administered two of the five anthraquinones simultaneously. Emodin, rhein, chrysophanol, and physcion all increase plasma exposure levels of aloe-emodin, while aloe-emodin lower their plasma exposure levels. (4) Conclusions: This experiment provides a certain preclinical basis for the study of anthraquinone aglycones against cerebral ischemia and a theoretical basis for the study of the mechanism of interaction between anthraquinones.
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Antraquinonas/administração & dosagem , Isquemia Encefálica/tratamento farmacológico , Rheum/química , Aloe/química , Animais , Antraquinonas/química , Antraquinonas/farmacocinética , Modelos Animais de Doenças , Quimioterapia Combinada , Emodina/administração & dosagem , Emodina/análogos & derivados , Emodina/química , Emodina/farmacocinética , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/farmacocinética , RatosRESUMO
Rhubarb is widely used in the treatment of obstipation, gastrointestinal indigestion and other diseases in China and other Asian countries for thousands of years. Anthraquinones are the major group of polyphenol constituents including aloe-emodin, rhein, emodin, chrysophanol and physcion. In order to evaluate the pharmacokinetics of five rhubarb anthraquinones, a high-performance liquid chromatography with fluorescence detection (HPLC-FLD) method for simultaneous determination of aloe-emodin, rhein, emodin, chrysophanol and physcion in dog plasma was established. Solid phase extraction (SPE) was applied to the extraction and purification of samples. The calibration curves of five anthraquinones showed good linearity with r greater than 0.9925. The average extraction recoveries, examined at three concentration levels, carried from 92.1% to 102.3%, and the accuracies ranged from 87.7% to 102.5% with precision (RSD) <10%. The pharmacokinetic paremeters of five anthraquinones were investigated systematically after orally administration the rhubarb extract. Five anthraquinones were rapidly absorbed and Tmax for aloe-emodin, rhein, emodin, chrysophanol and physcion was at 0.75, 1.50, 0.75, 1.0 and 2.0 h respectively. The Cmax of five anthraquinones was 0.031, 3.39, 0.27, 0.036 and 0.032 µg/mL while the AUC of five anthraquinones was 0.35 ± 0.058, 32.22 ± 8.29, 2.97 ± 0.66, 0.43 ± 0.10 and 0.41 ± 0.12 mg h/L, respectively.
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Antraquinonas/sangue , Cromatografia Líquida de Alta Pressão/métodos , Extratos Vegetais/farmacocinética , Administração Oral , Animais , Antraquinonas/farmacocinética , Cães , Masculino , Rheum , Extração em Fase SólidaRESUMO
The development of stable fluorescent sensors for toxic pollutants and drugs is meaningful to the environment and public health. In this work, nitrogen-doped graphene quantum dots (N-GQDs) were facially synthesized by a one-step hydrothermal method using soluble starch and l-arginine as carbon and nitrogen sources in pure water at 190 °C for 4 h. The as-synthesized N-GQDs were well characterized and displayed blue fluorescence emission at 445 nm with excellent pH stability, salt tolerance, thermostability, photobleaching resistance and reproducibility. Moreover, N-GQDs could serve as an "on-off" sensor for selective detection of Cr(vi) and folic acid with low detection limit (0.80 and 2.1 µM), good linear correlation over wide linear range (0-50 µM and 0-200 µM) as well as short response time (<10 s). The practical applications of N-GQDs for Cr(vi) and folic acid detection in actual samples were further investigated and showed acceptable recoveries (92-105%) with relative standard deviations less than 5%. These results indicated that this N-GQDs-based sensor could be a potential alternative for Cr(vi) and folic acid detection in the fields of environmental monitoring and drug analysis.
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A comparative oral pharmacokinetic study of five anthraquinones (aloe-emodin, emodin, rhein, chrysophanol and physcion) from the extract of Rheum palmatum L. was performed in normal and thrombotic focal cerebral ischemia (TFCI)-induced rats. The plasma samples were clarified through solid phase extraction prior to simultaneous determination of the anthraquinones with a validated high-performance liquid chromatography-fluorescence system. The results indicated that the Cmax, t(1/2) and AUC(0-t), of aloe-emodin, rhein, emodin and chrysophanol in TFCI-induced rats were nearly double, whereas the CL values were remarkably decreased (p < 0.05) over those of the normal rats. The plasma drug concentration-time data of five anthraquinones to rats fitted a two-compartment open model. The five anthraquinones in rat plasma were absorbed quickly and eliminated slowly in both groups. The obtained results could be helpful for evaluating the impact of the efficacy and safety of the drug in clinical applications.
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Antraquinonas/farmacocinética , Isquemia Encefálica/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacocinética , Extratos Vegetais/farmacocinética , Rheum/química , Animais , Cromatografia Líquida de Alta Pressão , Emodina/análogos & derivados , Emodina/farmacocinética , Masculino , Extratos Vegetais/química , Ratos , Ratos Sprague-DawleyRESUMO
Introduction: Acute lung injury (ALI) is a common and devastating respiratory disease associated with uncontrolled inflammatory response and transepithelial neutrophil migration. In recent years, a growing number of studies have found that Ardisiae Japonicae Herba (AJH) has a favorable anti-inflammatory effect. However, its serum material basis and molecular mechanism are still unknown in ALI treatment. In this study, metabolomics and network analysis of serum pharmacochemistry were used to explore the therapeutic effect and molecular mechanism of AJH against lipopolysaccharide (LPS)-induced ALI. Methods: A total of 12 rats for serum pharmacochemistry analysis were randomly divided into the LPS group and LPS + AJH-treated group (treated with AJH extract 20 g/kg/d), which were administered LPS (2 mg/kg) by intratracheal instillation and then continuously administered for 7 days. Moreover, 36 rats for metabolomic research were divided into control, LPS, LPS + AJH-treated (5, 10, and 20 g/kg/d), and LPS + dexamethasone (Dex) (2.3 × 10-4 g/kg/d) groups. After 1 h of the seventh administration, the LPS, LPS + AJH-treated, and LPS + Dex groups were administered LPS by intratracheal instillation to induce ALI. The serum pharmacochemistry profiling was performed by UPLC-Orbitrap Fusion MS to identify serum components, which further explore the molecular mechanism of AJH against ALI by network analysis. Meanwhile, metabolomics was used to select the potential biomarkers and related metabolic pathways and to analyze the therapeutic mechanism of AJH against ALI. Results: The results showed that 71 serum components and 18 related metabolites were identified in ALI rat serum. We found that 81 overlapping targets were frequently involved in AGE-RAGE, PI3K-AKT, and JAK-STAT signaling pathways in network analysis. The LPS + AJH-treated groups exerted protective effects against ALI by reducing the infiltration of inflammatory cells and achieved anti-inflammatory efficacy by significantly regulating the interleukin (IL)-6 and IL-10 levels. Metabolomics analysis shows that the therapeutic effect of AJH on ALI involves 43 potential biomarkers and 14 metabolic pathways, especially phenylalanine, tyrosine, and tryptophan biosynthesis and linoleic acid metabolism pathways, to be influenced, which implied the potential mechanism of AJH in ALI treatment. Discussion: Our study initially elucidated the material basis and effective mechanism of AJH against ALI, which provided a solid basis for AJH application.
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In this work, a 2-(2'-hydroxyphenyl)benzimidazole derived fluorescent probe, 2-(2'-hydroxy-4'-aminophenyl)benzimidazole (4-AHBI), was synthesized and its fluorescent behavior toward triphosgene were evaluated. The results showed that 4-AHBI exhibited high sensitivity (limit of detection, 0.08 nM) and excellent selectivity for triphosgene over other acyl chlorides including phosgene in CH2Cl2 solution. Moreover, 4-AHBI loaded test strips were prepared for the practical sensing of triphosgene.
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GEN-0828, a proposed clinical candidate for hemophilia and trauma hemorrhage treatment, is a novel recombinant activated human factor VII (rFVIIa). The purpose of this paper is to compare the pharmacokinetics and pharmacodynamics of GEN-0828 in hemophilia B mice with those of NovoSeven®, the only marketed rFVIIa product worldwide., GEN-0828 and NovoSeven® showed similar affinity bioactivity to recombinant tissue factor (rTF) in vitro. Pharmacodynamics data indicated a generally similar hemostatic efficacy (ED50) of GEN-0828 (10.91 KIU·kg-1) and NovoSeven® (18.91 KIU·kg-1) at the doses studied in hemophilia B mice, while GEN-0828 represented a lower initial effective dosage compared with that of NovoSeven® in terms of both blood loss and APTT. GEN-0828 exhibited linear pharmacokinetic profiles in hemophilia B mice at the 30-338 KIU·kg-1 dose range, the comparative pharmacokinetic study with NovoSeven® indicated better characteristics than NovoSeven® in terms of the appropriate higher maximal concentration (Cmax) and area under the plasma concentration-time curve (AUClast) and longer mean residence time (MRT). In conclusion, GEN-0828 was a promising new type of rFVIIa compound with favourable pharmacokinetic and pharmacodynamic profiles.
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Hemofilia A , Hemofilia B , Humanos , Animais , Camundongos , Hemofilia B/tratamento farmacológico , Fator VII/farmacocinética , Fator VII/uso terapêutico , Fator VIIa/uso terapêutico , Hemorragia/tratamento farmacológico , Proteínas RecombinantesRESUMO
Peimine and peiminine are isosteroidal alkaloids with multiple biological activities, such as anticancer and anti-inflammatory activities, but their cellular uptake and pharmacodynamics are unclear. In this study, a rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous quantification of peimine and peiminine concentrations in A549 cells. In the pharmacodynamic study, the selected inflammatory cytokines were IL-8, MMP-9, and TIMP-1. The results demonstrated that all calibration curves exhibited good linearity (r > 0.9970). The RSDs of intraday and interday precision and accuracy were less than 6.73% and 1.76% and 7.73% and 3.05% for peimine and peiminine, respectively. Moreover, the average analytic recoveries ranged from 83.85% to 113.67%, and the matrix effect was within 95.05%-111.29%. The uptake experiment showed a time-dependent characteristic in the A549 cells. The combination group had increased uptake and had a longer T max than the single group. In the experimental pharmacodynamics groups, the anti-inflammatory effects of the 100.0 µg/mL combination group were the most obvious. This investigation, for the first time, explores the cellular uptake profiles and pharmacodynamics of peimine and peiminine in A549 cell lines.
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Jinshui Huanxian granules (JSHX) is a clinical Chinese medicine formula used for treating pulmonary fibrosis (PF). However, the effective components and molecular mechanisms of JSHX are still unclear. In this study, a combination approach using ultra-high performance liquid chromatography-Orbitrap Fusion mass spectrometry (UPLC-Orbitrap Fusion MS) integrated with network pharmacology was followed to identify the components of JSHX and the underlying molecular mechanisms against PF. UPLC-Orbitrap Fusion MS was used to identify the components present in JSHX. On the basis of the identified components, we performed target prediction using the SwissTargetPrediction database, protein-protein interaction (PPI) analysis using STRING database, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis using Metascape and constructed a component-target-pathway network using Cytoscape 3.7.2. Molecular docking technology was used to verify the affinity between the core components and targets. Finally, the pharmacological activities of three potentially bioactive components were validated in transforming growth factor ß1 (TGF-ß1)-induced A549 cell fibrosis model. As a result, we identified 266 components, including 56 flavonoids, 52 saponins, 31 alkaloids, 10 coumarins, 12 terpenoids and 105 other components. Of these, 90 validated components were predicted to act on 172 PF-related targets and they exhibited therapeutic effects against PF via regulation of cell migration, regulation of the mitogen-activated protein kinase (MAPK) cascade, reduction of oxidative stress, and anti-inflammatory activity. Molecular docking showed that the core components could spontaneously bind to receptor proteins with a strong binding force. In vitro, compared to model group, hesperetin, ruscogenin and liquiritin significantly inhibited the increase of α-smooth muscle actin (α-SMA) and fibronectin (FN) and the decrease of e-cadherin (E-cad) in TGF-ß1-induced A549 cells. This study is the first to show, using UPLC-Orbitrap Fusion MS combined with network pharmacology and experimental validation, that JSHX might exert therapeutic actions against PF by suppressing the expression of key factors in PF. The findings provide a deeper understanding of the chemical profiling and pharmacological activities of JSHX and a reference for further scientific research and clinical use of JSHX in PF treatment.
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Medicamentos de Ervas Chinesas , Fibrose Pulmonar , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Humanos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fibrose Pulmonar/tratamento farmacológico , Fator de Crescimento Transformador beta1RESUMO
Acute-exacerbation chronic obstructive pulmonary disease (AECOPD) is mainly associated with acute respiratory tract infection. In recent years, a growing number of studies have found that Tanreqing capsule (TRQ) has a favorable anti-inflammatory effect. In this study, we used network pharmacology and pharmacodynamics to explore the molecular mechanism and effects of TRQ in AECOPD treatment. To further understand the molecular mechanism of TRQ in AECOPD treatment, we used the network pharmacology to predict components of TRQ, TRQ-related targets, AECOPD-related targets, and pathways. In addition, we used the cigarette-smoke/lipopolysaccharide -induced AECOPD experimental model in Sprague-Dawley rats (72 rats randomly divided into six groups [n = 12 each]: control, model, high-TRQ [TRQ-H], medium-TRQ [TRQ-M], low-TRQ, and dexamethasone [Dex]) to evaluate the therapeutic effects of TRQ and to verify the network pharmacology. We found that 59 overlapping targets based on component-and AECOPD-related targets were frequently involved in the advanced glycation end product-receptor for advanced glycation end product signaling pathway in diabetic complications, the phosphatidylinositol-3-kinase-protein kinase B signaling pathway, and the hypoxia-inducible factor 1 signaling pathway, which might play important roles in the anti-inflammatory mechanism of TRQ in AECOPD treatment. Moreover, TRQ groups exerted protective effects against AECOPD by reducing the infiltration of inflammatory cells. Meanwhile, TRQ-M and TRQ-H groups significantly downregulated or upregulated the expression of tumor necrosis factor, interleukin (IL) 6, C-reactive protein, IL10, and serum amyloid A, as key targets in network pharmacology, in the serum and bronchoalveolar lavage fluid to achieve anti-inflammatory efficacy. Our study showed that TRQ had better anti-inflammatory efficacy against AECOPD, and initially elucidated its molecular mechanism. Moreover, our study also provides a new strategy to explore effective mechanism of TRQ against AECOPD; and further studies are needed to validate the biological processes and pathways of TRQ against AECOPD.
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Farmacologia em Rede , Doença Pulmonar Obstrutiva Crônica , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Medicamentos de Ervas Chinesas , Interleucina-6 , Doença Pulmonar Obstrutiva Crônica/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The Bu-Fei formula (BFF) has a positive effect on chronic obstructive pulmonary disease (COPD). However, its therapeutic mechanisms against COPD remain unknown. AIM OF THE STUDY: To explore BFF's therapeutic effect on COPD and pharmacological mechanisms. MATERIALS AND METHODS: First, the effect of BFF on rats with COPD was studied. Rats were randomly assigned to the blank, COPD, BFF treatment, and aminophylline (APL) treatment groups. From weeks 1-8, the COPD model was established by Klebsiella pneumoniae (KP) and cigarette smoke. Then, rats were given corresponding treatment for 8 weeks. The lung function of the rats was analyzed by whole-body plethysmography and pulmonary function testing, lung histopathology by electron microscopy and hematoxylin and eosin staining, and protein levels by immunohistochemistry. Next, the key components and targets of BFF in COPD were screened by network pharmacology analysis. Finally, the possible mechanism was verified through molecular docking and in vivo experiments. RESULTS: BFF significantly improved lung function and lung histopathology in COPD rats and inhibit inflammation and collagen deposition in lung tissues. Also, 46 bioactive compounds and 136 BFF targets related to COPD were identified; among them, 3 compounds (quercetin, luteolin, and nobiletin) and 6 core targets (Akt1, BCL2, NF-κB p65, VEGFA, MMP9, and Caspase 8) were the key molecules associated with the mechanisms of BFF. The target enrichment analysis suggested that BFF's mechanisms might involve the apoptosis-related pathway; this possibility was supported by the molecular docking data. Lastly, BFF was indicated to increase the expression of core target genes and the production of apoptosis-related proteins. CONCLUSIONS: BFF affects COPD by regulating the apoptosis-related pathways and targets.
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Apoptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Animais , Colágeno/metabolismo , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Inflamação/patologia , Farmacologia em Rede , Ratos , Ratos Sprague-Dawley , Testes de Função RespiratóriaRESUMO
Combining traditional Chinese medicine and chemical drugs with antimicrobial activities has become more popular, but there is insufficient relevant research on such combinations. The Tanreqing injection (TRQI), a Chinese compound medicine, exhibits therapeutic effects in treating upper respiratory tract infections, severe influenza, and pneumonia. This research investigates the pharmacokinetics of TRQI in pneumonia model rats and explores the effect of the antibiotic cefixime on its metabolism. The pneumonia model rats were randomly divided into six groups: low, medium, and high (3, 6, and 12 mL kg-1) dose TRQI group, and a medium dose TRQI combined with cefixime (14.4 mg kg-1) group, with the remainder two groups were control group. Blood samples were collected from the tail vein at different time points between 0 and 24 h after injection. A sensitive and quick method based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established for the simultaneous determination of the 13 TRQI components in the blood samples. The analytes were separated on an XBridge™C18 column (2.1 mm × 150 mm, 5 µm), with the flow phase consisting of methanol and 0.1% formic acid water at a flow rate of 0.3 mL/min. The assay method met the biological sample determination requirements, demonstrating good adaptability and practicability for application in the pharmacokinetic study of TRQI in pneumonia model rats. Moreover, the method was used successfully in the interaction study of TRQI with cefixime. The results indicated that co-administration results in a significant change in the pharmacokinetic parameters of the main TRQI components. However, the changes in the pharmacokinetic characteristics of multiple TRQI components were inconsistent. Thus, the results of this drug combination under different pathological conditions in clinical applications were unpredictable. Therefore, more attention should be paid to the combined use of cefixime and TRQI in clinical applications to avoid the risk of adverse drug reactions in future studies.
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Cefixima/farmacocinética , Medicamentos de Ervas Chinesas , Pneumonia , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Interações Medicamentosas , Medicamentos de Ervas Chinesas/farmacocinética , Pneumonia/tratamento farmacológico , Ratos , Espectrometria de Massas em TandemRESUMO
In this work, an ESIPT-based fluorescence probe, 5'-amino-2-(2'-hydroxyphenyl)benzimidazole (P1), was synthesized and explored for the ratiometric detection of phosgene. Compared to 2-(2'-hydroxyphenyl)benzimidazole (HBI), P1 exhibits high sensitivity (LoD = 5.3 nM) and selectivity toward phosgene with the introduction of the amine group. Furthermore, simple P1 loaded test papers are manufactured and display selective fluorescent detection of phosgene in the gas phase.
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OBJECTIVE: To study the mechanistic effects of Tiaobu Feishen therapy (TBFS) on inflammation induced by cigarette smoke extract (CSE) in a human monocyte/macrophage cell line. METHODS: The human monocyte/macrophage cell line THP-1 was stimulated with 10 % CSE in the presence or absence of Bufei Yishen formula (BYF), Bufei Jianpi formula (BJF) and Yiqi Zishen formula (YZF). All formulations contained serum. Pro-inflammatory cytokines were measured in the supernatants using enzyme-linked immunosorbent assay. The activity of STAT3 DNA binding was detected using electrophoretic mobility shift assay and janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway activation was assessed using Western blotting. RESULTS: The results showed that BYF, BJF and YZF treatment strongly decreased the CSE-induced secretion of interleukin (IL)-6, IL-8, tumor necrosis factor-α and matrix metalloproteinase-9 by THP-1 cells. Furthermore, BYF, BJF and YZF treatment attenuated STAT3 DNA binding capacity and JAK2 and STAT3 were shown to be phosphorylated. CONCLUSION: The data revealed that BYF, BJF and YZF effectively inhibited a CSE-induced inflammatory response in THP-1 cells by limiting activation of the JAK2/STAT3 pathway.
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Inflamação , Monócitos , Linhagem Celular , Humanos , Inflamação/tratamento farmacológico , Inflamação/genética , Macrófagos/metabolismo , Monócitos/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , FumarRESUMO
OBJECTIVE: Critical effective constituents were identified from Bufei Yishen formula (BYF), a traditional herbal compound and combined as effective-constituent compatibility (ECC) of BYF I, which may have potential bioactive equivalence to BYF. METHODS: The active constituents of BYF were identified using four cellular models and categorised into Groups 1 (Bufeiqi), 2 (Bushen), 3 (Huatan) and 4 (Huoxue) according to Chinese medicinal theory. An orthogonal design and a combination method were used to determine the optimal ratios of effective constituents in each group and the ratios of "Groups 1 to 4" according to their pharmacological activity. We also comprehensively assessed bioactive equivalence between the BYF and the ECC of BYF I in a rat model of chronic obstructive pulmonary disease (COPD). RESULTS: We identified 12 active constituents in BYF. The numbers of constituents in Groups 1 to 4 were 3, 2, 5 and 2, respectively. We identified the optimal ratios of effective constituents within each group. In Group 1, total ginsenosides:Astragalus polysaccharide:astragaloside IV ratio was 9:5:2. In Group 2, icariin:schisandrin B ratio was 100:12.5. In Group 3, nobiletin:hesperidin:peimine:peiminine:kaempferol ratio was 4:30:6.25:0:0. In Group 4, paeoniflorin:paeonol ratio was 4:1. An orthogonal design was then used to establish the optimal ratios of Group 1, Group 2, Group 3 and Group 4 in ECC of BYF I. The ratio for total ginsenosides:Astragalus polysaccharide:astragaloside IV:icariin:schisandrin B:nobiletin:hesperidin:peimine:paeoniflorin:paeonol was determined to be 22.5:12.5:5:100:12.5:4:30:6.25:25:6.25. A comprehensive evaluation confirmed that ECC of BYF I presented with bioactive equivalence to the original BYF. CONCLUSION: Based on the ECC of traditional Chinese medicine formula method, the effective constituents of BYF were identified and combined in a fixed ratio as ECC of BYF I that was as effective as BYF itself in treating rats with COPD.