RESUMO
This study aims to explore the potential metabolic pathways and targets of Puerariae Thomsonii Radix in the clinical treatment of mild dyslipidemia. UPLC-Q-TOF-MS and EASY-nLC-timsTOF-Pro2 were employed to perform metabolomic and proteomic analyses of the plasma samples collected from the patients with mild dyslipidemia at baseline and after 12 weeks of treatment with Puerariae Thomsonii Radix. The multivariate statistical analysis was carried out for comparison between groups, and the correlation analysis was performed for the metabolites and proteins closely related to mild dyslipidemia with the blood lipid indexes. The possible pathways and targets for mitigating mild dyslipidemia were screened out by the Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis. The results showed that 56 differential metabolites and 78 differential proteins in the plasma of patients were associated with Puerariae Thomsonii Radix treatment. In addition, changes were detected for the proteins or metabolites(ApoB-100, 9,10-DHOME, GAPDH, PGK1, PGAM1, ENO1, etc.) involved in lipoprotein, lipid, and glucose metabolism and the proteins or metabolites(oxidized phospholipid, PLA2G7, LTA4H, etc.) related to inflammation and oxidative stress. Puerariae Thomsonii Radix may down-regulate the overexpression of ApoB-100, activate the peroxisome proliferator-activated receptor α/γ(PPARα/γ), promote the catabolism of fat and glycerol, and alleviate the oxidative stress mediated by oxidized phospholipids and leukotriene B4(LTB4) in the treatment of mild dyslipidemia.
Assuntos
Medicamentos de Ervas Chinesas , Dislipidemias , Metabolômica , Proteômica , Pueraria , Humanos , Dislipidemias/tratamento farmacológico , Dislipidemias/genética , Dislipidemias/metabolismo , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Pueraria/química , Masculino , Feminino , Pessoa de Meia-Idade , AdultoRESUMO
Liver, as an immune and detoxification organ, represents an important line of defense against bacteria and infection and a vulnerable organ that is easily injured during sepsis. Artesunate (ART) is an anti-malaria agent, that also exhibits broad pharmacological activities including anti-inflammatory, immune-regulation and liver protection. In this study, we investigated the cellular responses in liver to sepsis infection and ART hepatic-protective mechanisms against sepsis. Cecal ligation and puncture (CLP)-induced sepsis model was established in mice. The mice were administered ART (10 mg/kg, i.p.) at 4 h, and sacrificed at 12 h after the surgery. Liver samples were collected for preparing single-cell RNA transcriptome sequencing (scRNA-seq). The scRNA-seq analysis revealed that sepsis-induced a dramatic reduction of hepatic endothelial cells, especially the subtypes characterized with proliferation and differentiation. Macrophages were recruited during sepsis and released inflammatory cytokines (Tnf, Il1b, Il6), chemokines (Ccl6, Cd14), and transcription factor (Nfkb1), resulting in liver inflammatory responses. Massive apoptosis of lymphocytes and abnormal recruitment of neutrophils caused immune dysfunction. ART treatment significantly improved the survival of CLP mice within 96 h, and partially relieved or reversed the above-mentioned pathological features, mitigating the impact of sepsis on liver injury, inflammation, and dysfunction. This study provides comprehensive fundamental proof for the liver protective efficacy of ART against sepsis infection, which would potentially contribute to its clinical translation for sepsis therapy. Single cell transcriptome reveals the changes of various hepatocyte subtypes of CLP-induced liver injury and the potential pharmacological effects of artesunate on sepsis.
Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Sepse , Camundongos , Animais , Artesunato/uso terapêutico , Células Endoteliais/patologia , Sepse/complicações , Sepse/tratamento farmacológico , Análise de Sequência de RNARESUMO
Three new compounds, (8S)-2,2,7,7-tetramethyl-8-hydroxymethyl-6H-indanone-(2,3-b)-2H-pyran-9-O-ß-d-glucopyranoside (1), (7S,8S)-2,2,7-trimethyl-7-hydroxymethyl-8-hydroxy-2,7,8,9-tetrahydro-6H-naphtho-(2,3-b)-pyran-10-O-ß-d-glucopyranoside (2), 1-deoxy-1-(3,4-dihydro-7-methyl-2,3-dioxo-1(2H)-quinoxalinyl)pentitol-6-carboxylic acid (3), as well as six known compounds (4-9), were obtained. Their structures were determined by spectroscopy and comparison with NMR data of related compounds. Absolute configurations were determined by ECD spectroscopy. The hepatoprotective effects of these compounds were investigated on HepG2 and LO2 cells lines; compounds 1, 2, and 4 displayed moderate activity.
Assuntos
Glicosídeos , Estrutura Molecular , Glicosídeos/química , Linhagem Celular , Espectroscopia de Ressonância MagnéticaRESUMO
The study aimed to investigate the effect of anemoside B4(B4) on fatty acid metabolism in mice with colitis-associated cancer(CAC). The CAC model was established by azoxymethane(AOM)/dextran sodium sulfate(DSS) in mice. Mice were randomly divided into a normal group, a model group, and low-, medium-, and high-dose anemoside B4 groups. After the experiment, the length of the mouse colon and the size of the tumor were measured, and the pathological alterations in the mouse colon were observed using hematoxylin-eosin(HE) staining. The slices of the colon tumor were obtained for spatial metabolome analysis to analyze the distribution of fatty acid metabolism-related substances in the tumor. The mRNA levels of SREBP-1, FAS, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 were determined by real-time quantitative PCR(RT-qPCR). The results revealed that the model group showed decreased body weight(P<0.05) and colon length(P<0.001), increased number of tumors, and increased pathological score(P<0.01). Spatial metabolome analysis revealed that the content of fatty acids and their derivatives, carnitine, and phospholipid in the colon tumor was increased. RT-qPCR results indicated that fatty acid de novo synthesis and ß-oxidation-related genes, such as SREBP-1, FASN, ACCα, SCD-1, ACOX, UCP-2, and CPT-1 mRNA expression levels increased considerably(P<0.05, P<0.001). After anemoside B4 administration, the colon length increased(P<0.01), and the number of tumors decreased in the high-dose anemoside B4 group(P<0.05). Additionally, spatial metabolome analysis showed that anemoside B4 could decrease the content of fatty acids and their derivatives, carnitine, and phospholipids in colon tumors. Meanwhile, anemoside B4 could also down-regulate the expression of FASN, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 in the colon(P<0.05, P<0.01, P<0.001). The findings of this study show that anemoside B4 may inhibit CAC via regulating fatty acid metabolism reprogramming.
Assuntos
Neoplasias Associadas a Colite , Colite , Neoplasias do Colo , Camundongos , Animais , Proteína de Ligação a Elemento Regulador de Esterol 1 , PPAR alfa/genética , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Colo , Azoximetano , RNA Mensageiro , Sulfato de Dextrana , Colite/induzido quimicamente , Colite/complicações , Colite/tratamento farmacológico , Camundongos Endogâmicos C57BL , Modelos Animais de DoençasRESUMO
Ajania belonging to the subtribe Artemisiinae of Anthemideae(Asteraceae) is a genus of semi-shrubs closely related to Chrysanthemum. There are 24 species of Ajania in northwestern China, most of which are folk herbal medicines with strong stress tolerance. Modern medical studies have demonstrated that the chemical constituents of Ajania mainly include terpenoids, flavonoids, phenylpropanoids, alkynes, and essential oils. These compounds endow the plants with antimicrobial, anti-inflammatory, antitumor, antimalarial, antioxidant, and insecticide effects. In this study, we reviewed the research progress in the chemical constituents and pharmacological activities of Ajania, aiming to provide reference for the further research and development of Ajania.
Assuntos
Antimaláricos , Asteraceae , Chrysanthemum , Alcinos , Antioxidantes/farmacologiaRESUMO
Three new saponins (1-3), a new natural product (4) and six other known compounds (5-10) were isolated from the whole Reineckia carnea plant. Their structures were established by comparison of their NMR spectra and MS data with literature data. In addition, all the isolated compounds were evaluated in vitro for anti-inflammatory activities against LPS-stimulated nitric oxide (NO) production in RAW 264.7 macrophages. Compounds 1-4 exhibited anti-inflammatory activities with IC50 values of 37.5 µM, 31.4 µM, 34.6 µM, and 56.1 µM, respectively. Furthermore, compounds 5-10 showed anti-inflammatory activities with IC50 values ranging from 20.3 to 42.9 µM.
Assuntos
Anti-Inflamatórios , Saponinas , Lipopolissacarídeos , Macrófagos , Estrutura Molecular , Óxido Nítrico , Extratos VegetaisRESUMO
This paper was aimed to observe the effect of anemoside B4(hereinafter referred to as B4) on cisplatin-induced acute kidney injury in mice, and to investigate its possible mechanism in renal protection from inflammation and apoptosis aspects. Mice were divided into normal group, model group, dexamethasone positive group and B4 high, middle and low dose groups(5, 2.5, and 1.25 mg·kg~(-1 )doses). All the other mice groups except normal group were given with tail vein injection of cisplatin(15 mg·kg~(-1)) to induce acute kidney injury models. The drug administration was started on the day of modeling, and lasted for 4 days. After 1 hour of the last injection, orbital blood was collected. After the serum was separated, serum urea nitrogen(BUN), creatinine(Cre), total protein(TP), and albumin(ALB) were tested by using an automatic biochemical analyzer; the changes of kidney pathological morphology were observed by PAS staining; the protein expression levels of inflammatory factors including nucleotide binding oligomerization domain-like receptor(NLRP3), cysteinyl aspartate specific proteinase 1(caspase-1), interleukin-18(IL-18), interleukin-1ß(IL-1ß), tumor necrosis factor(TNF-α), and interleukin-6(IL-6) and apoptosis factors including p53, caspase-3, cleaved-caspase-3, Bcl-2 associated X protein(Bax), and B-cell lymphoma-2(Bcl-2) were analyzed by Western blot. The results showed that B4 significantly reduced the serum BUN and Cre contents, and alleviated pathological changes in renal tissues, such as the shedding and degeneration of renal tubular epithelial cells, tubulin tubule type. B4 significantly down-regulated the protein expressions of p53, Bax, cleaved-caspase-3 in the kidney and up-regulated the expression of Bcl-2/Bax. In model group, however, no significant up-regulation was observed in the protein expression levels of inflammatory cytokines(NLRP3, pro-caspase-1, IL-18, IL-1ß, TNF-α, IL-6). The results suggested that B4 had a certain protective effect on cisplatin-induced acute kidney injury, and could activate p53 signaling pathway related apoptotic factors. B4 renal protective effect was mainly related to the regulation of p53 signaling pathway, while NLRP3 inflammasome and related inflammatory factors had no obvious response in this model.
Assuntos
Injúria Renal Aguda/tratamento farmacológico , Apoptose , Inflamação , Saponinas/uso terapêutico , Injúria Renal Aguda/induzido quimicamente , Animais , Proteínas Reguladoras de Apoptose , Citocinas , Rim , CamundongosRESUMO
The aim of this paper was to investigate the effect and mechanism of anemoside B4 on renal ischemia reperfusion injury in rats. A total of 50 rats were randomly divided into the model group(NS) and anemoside B4 low-dose(1.25 mg·kg~(-1)), medium-dose(2.5 mg·kg~(-1)) and high-dose(5 mg·kg~(-1)) groups after the right kidney was removed and the left kidney was ligated to make the ischemia reperfusion model. Another 10 rats were selected as sham operation group only for normal control group(NS, received normal saline). Automatic biochemical analyzer was used to measure serum blood urea nitrogen(BUN), creatinine(Cre), cerebrospinal fluid(CSF) and urinemicroalbumin(mALB) levels after 5 days of tail vein injection treament. Total urine protein and total urinary albu-min were calculated and kidney samples were collected. Histopathological changes of renal tissues were observed by PAS staining. Western blot analysis was performed to detect the protein expressions of TLR4 and NF-κB in renal inflammatory factors related to NLRP3 pathway and TLR4/NF-κB pathway. The results showed that the levels of BUN, Cre, urinary total protein and urinary total albumin in the model group were significantly increased(P<0.01), with severe renal tubule injury was serious, manifested by obvious expansion of renal tubules, more serious tubular proteins, and some tubular epithelial cells were exfoliated. At the same time, the expression of inflammatory factors related to NLRP3 pathway and TLR4/NF-κB pathway increased significantly(P<0.01 or P<0.05). The levels of BUN, Cre were reduced in different doses of anemoside B4(P<0.05). The levels of total urinary protein and total urinary albumin were decreased in the low and high dose groups of anemoside B4.The level of total urinary albumin in the high-dose group of anemoside B4 was significantly reduced(P<0.05).Renal tubular injury was alleviated, tubular epithelial cell exfoliation was reduced, and the expression of related inflammatory factors was reduced in different degrees(P<0.01 or P<0.05). This study showed that anemoside B4 could alleviate renal ischemia-reperfusion injury in rats. And its mechanism may be related to the inhibition of inflammatory factors related to response mediated by NLRP3 pathway and TLR4/NF-κB pathway by anemoside B4.
Assuntos
Artéria Renal/patologia , Traumatismo por Reperfusão/tratamento farmacológico , Saponinas/uso terapêutico , Transdução de Sinais , Animais , Rim , Ligadura , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos , Receptor 4 Toll-Like/metabolismoRESUMO
Dihydrotanshinone (DHT), one of the major ingredients of Salvia miltiorrhiza Bunge (Danshen), displays many bioactivities. However, the activity and underlying mechanism of DHT in anti-inflammation have not yet been elucidated. In this study, we investigated the anti-inflammatory activity and molecular mechanism of action of DHT both in vitro and in vivo. Our data showed that DHT significantly decreased the release of inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1ß in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, THP-1 cells, and bone marrow-derived macrophages (BMDMs), and altered the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). In addition, flow cytometry results indicated that DHT reduced the calcium influx, and generation of reactive oxygen species (ROS), and nitric oxide (NO) generation in LPS-stimulated RAW264.7 cells. Moreover, DHT suppressed the transcription of nuclear factor-κB (NF-κB), the expressions of NF-κB proteins, and nuclear translocation of NF-κB/p65, thereby suggesting that the NF-κB pathway played a role in the anti-inflammatory action of DHT. In addition, DHT attenuated LPS-challenged activator protein-1 (AP-1) activity, resulting from interference of the mitogen-activated protein kinase (MAPK) pathway. The molecular docking simulation of DHT to toll-like receptor 4 (TLR4) suggested that DHT binds to the active sites of TLR4 to block TLR4 dimerization, which was further corroborated by cellular thermal shift assay and co-immunoprecipitation (Co-IP) experiments. Furthermore, the recruitment of myeloid differentiation primary response gene 88 (MyD88) and the expression of transforming growth factor-b (TGF-b)-activated kinase 1 (p-TAK1) were disturbed by the inhibition of TLR4 dimerization. Thus, investigating the molecular mechanism of DHT indicated that TLR4-MyD88-NF-κB/MAPK signaling cascades were involved in the anti-inflammatory activity of DHT in vitro. In in vivo mouse models, DHT significantly ameliorated LPS-challenged acute kidney injury, inhibited dimethylbenzene-induced mouse ear oedema, and rescued LPS-induced sepsis in mice. Taken together, our results indicated that DHT exhibited significant anti-inflammatory activity both in vitro and in vivo, suggesting that DHT may be a potential therapeutic agent for inflammatory diseases.
Assuntos
Anti-Inflamatórios/farmacologia , Fenantrenos/farmacologia , Receptor 4 Toll-Like/metabolismo , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Animais , Anti-Inflamatórios/uso terapêutico , Citocinas/genética , Citocinas/metabolismo , Dimerização , Edema/induzido quimicamente , Edema/tratamento farmacológico , Furanos , Células HEK293 , Humanos , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Fenantrenos/uso terapêutico , Quinonas , Células RAW 264.7 , Sepse/induzido quimicamente , Sepse/tratamento farmacológico , Células THP-1 , XilenosRESUMO
In this study,in-depth systematic evaluation of rat of acute kidney injury(AKI) caused by renal arteriovenous ligation was conducted to better master and apply this model for drug research. Male SD rats of 2-3 months old were employed in this study.The left kidney was removed,and the right kidney received ligation for 40 min and reperfusion for 24 h. Serum creatinine(Crea),urea nitrogen(BUN) and the renal tissue sections were assayed as the basic indicators to evaluate their renal function. The mRNA expression of inflammatory necrosis factors and apoptotic factors was used to evaluate the mechanism of molecular pathophysiological changes. The results showed that the serum Crea and BUN caused by ligation of both renal arteries and veins were significantly higher than those of rats with renal artery ligation. After renal arteriovenous ligation for 40 min and reperfusion for 24 h in rats,the serum Crea of the rats varied from less than 100 µmol·L-1 to more than 430 µmol·L-1. Among them,5 rats showed less than 100 µmol·L-1 serum Crea,20 rats with 100-200 µmol·L-1 serum Crea and 12 rats with more than 430 µmol·L-1. Rats with serum Crea between 300-430 µmol·L-1 accounted for 66.3%(122/184) of the total number of the experiment rats. After 72 h reperfusion,serum Crea in the group of Crea 370-430 µmol·L-1 continued to increase,while the serum Crea in the group of Crea 200-300 µmol·L-1 and the group of Crea 300-370 µmol·L-1 recovered quickly. No matter serum Crea was elevated or decreased,the renal tubules showed pathological changes such as vacuolar degeneration or even necrosis. The mRNA expression levels of Toll-like receptor(TLR4),tumor necrosis factor(TNF-α) and interleukin(IL-6) in renal tissueswere significantly up-regulated,and the effect was most obvious in the group of serum Crea 370-430 µmol·L-1. The study indicated that the model for AKI caused by renal arteriovenous ligation and reperfusion is easy to operate,and the serum Crea and BUN have the characteristics of continuous increase,beneficial to the observation of drug effects. This acute kidney injury is mainly related to the pathophysiological response of inflammatory necrosis.
Assuntos
Injúria Renal Aguda/patologia , Traumatismo por Reperfusão , Animais , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Modelos Animais de Doenças , Rim/patologia , Túbulos Renais/patologia , Ligadura , Masculino , Ratos , Ratos Sprague-Dawley , Artéria RenalRESUMO
Ziyuglycoside I (ZGS1) is a promising drug candidate for the treatment of leucopenia. Currently, information on ZGS1 and its in vivo metabolite ziyuglycoside II (ZGS2) is limited. The objective of this study was to investigate the pharmacokinetics, tissue distribution, and excretion of ziyuglycoside I (ZGS1) and its metabolite ziyuglycoside II (ZGS2) in rats. In our study, a simple and sensitive high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method was established for simultaneous determination of ZGS1 and its metabolite for Sprague-Dawley rat pharmacokinetics studies. The method was validated following internationally-approved guidelines. The results presented in this study indicated that subcutaneous administration of ZGS1 prolonged its extension time and increased the area under the curve (AUC0-t) of ZGS2 during 0 to t minutes. In summary, in this study, the pharmacokinetic characteristics of ZGS1 and its metabolite ZGS2 were defined and its tissue distribution, and excretion in rats were described. Our finding may be beneficial for leucopenia drug that focus on ZGS1.
Assuntos
Cromatografia Líquida de Alta Pressão , Saponinas/farmacocinética , Espectrometria de Massas em Tandem , Animais , Estrutura Molecular , Ratos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Análise Espectral , Distribuição TecidualRESUMO
Internal environment of metabolism of traditional Chinese medicine (TCM) is a dynamic process, which is in line with the "holistic-dynamic-comprehensive-analytic" characteristics of metabonomics, therefore metabonomics have a unique advantage to reveal the metabolic pattern of TCM. The application of metabonomics in TCM has great practical significance in understanding the pharmacodynamic/toxic effect material basis, mechanisms and guiding for determination of dosage and treatment course; At the same time, the scientific compatibility of TCM prescription, the germplasm resources of TCM and the preclinical safety/toxicity can be widely researched. At present, metabolomics has become a leading technology in many industries and fields including the research and development of TCM. The core of metabolomics is analytical technology, because comprehensive metabolite profiles or accurate identification of known metabolites can be obtained from complex biological samples only by appropriate analytical techniques. At the same time, a series of bioinformatics/chemical informatics/stoichiometry methods are needed to process the data, so as to obtain the potential law and information in the mass data. In this paper, the concept of metabolomics, relevant analytical techniques, data processing methods and applications were explained and analyzed clearly. In addition, the core problems and countermeasures of metabolomics were summarized, and the future development of metabolomics was prospected as well.
Assuntos
Medicina Tradicional Chinesa , Metabolômica , Pesquisa/tendências , Biologia Computacional , HumanosRESUMO
Scopolin (SC-1), scopoletin (SC-2) and isofraxidin (IS-1) are the main active constituents in Chimonanthi Radix. However, the in vivo metabolism of SC-1, SC-2 and IS-1 have not been comprehensively clarified. In this study, the in vivo metabolic profiles of these three coumarins in the rat plasma, urine and feces were analyzed. Ultra-high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS/MS) method was applied to characterize the prototypes and metabolites of SC-1, SC-2 and IS-1 in rat feces, urine, and plasma after intravenous administration. A total of 11 metabolites of the three parent compounds were tentatively identified. The main metabolic pathways were analyzed by identification of metabolites, and it was found that these three coumarins underwent multiple in vivo metabolic reactions including glucuronidation, sulfonation, isomerism and reduction. In this study, the analysis of metabolites of three coumarins basically demonstrated their in vivo metabolic process, providing basis for the further pharmacokinetics and pharmacological evaluations of SC-1, SC-2 and IS-1.
Assuntos
Calycanthaceae/química , Cumarínicos/metabolismo , Medicamentos de Ervas Chinesas/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Cumarínicos/farmacocinética , Medicamentos de Ervas Chinesas/farmacocinética , Ratos , Espectrometria de Massas em TandemRESUMO
A rapid and accurate method of UFLC-Q-TOF-MS/MS combined with multivariate statistical analysis was established for the identification of Ainsliaea fragrans from different origins in this study. The A. fragrans from different producing areas of Jiangxi, Yunnan, Henan and Jiangsu were determined by UFLC-Q-TOF-MS/MS in the negative ion mode. And the data of the study were analyzed by the Markerview and other software for the PCA and OPLS-DA cluster analysis as well as t test. The results of the principal component analysis(PCA)showed that the main components from different origins were well distinguished. And the results of multivariate statistical showed the differences and similarities between different producing areas. Besides, 40 different compounds were identified in the negative ion mode. This method for identifying A. fragrans from different producing areas has the advantages of rapid accuracy and simplicity, which laid the foundation for the evaluation of the quality of the A. fragrans.
Assuntos
Asteraceae/química , Medicamentos de Ervas Chinesas/química , China , Cromatografia Líquida de Alta Pressão , Compostos Fitoquímicos/análise , Análise de Componente Principal , Espectrometria de Massas em TandemRESUMO
BACKGROUND: As-needed formoterol can effectively relieve asthma symptoms. Since budesonide/formoterol is available as maintenance and reliever therapy in Asia, formoterol is now being used as-needed, but always with concomitant inhaled corticosteroids. The objective of this analysis was to assess the safety and efficacy of formoterol therapy in patients in East Asia (China, Indonesia, Korea, the Philippines and Singapore) with asthma. METHODS: Post-hoc analyses of data from the East Asian population of the RELIEF (REal LIfe EFfectiveness of Oxis® Turbuhaler® as-needed in asthmatic patients; study identification code: SD-037-0699) study were performed. RESULTS: This sub-group comprised 2834 randomised patients (formoterol n = 1418; salbutamol n = 1416) with mean age 35 years; 50.7% were male. 2678 patients completed the study. There was no significant difference in the total number of adverse events (AEs) reported in the formoterol and salbutamol groups (21.3% vs 20.9% of patients; p = 0.813), nor in the total number of serious AEs and/or discontinuations due to AEs (4.6% vs 5.5%, respectively; p = 0.323). Compared with salbutamol, formoterol was associated with a significantly longer time to first exacerbation (hazard ratio 0.86; p = 0.023) and a 14% reduction in the risk of any exacerbation (p < 0.05). Relative to salbutamol, mean adjusted reliever medication use throughout the study was significantly lower in the formoterol group (p = 0.017) and the risk of increased asthma medication use was 20% lower with formoterol (p = 0.005). CONCLUSIONS: Among patients with asthma in East Asia, as-needed formoterol and salbutamol had similar safety profiles but, compared with salbutamol, formoterol reduced the risk of exacerbations, increased the time to first exacerbation and reduced the need for reliever medication.
Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Albuterol/uso terapêutico , Asma/tratamento farmacológico , Fumarato de Formoterol/uso terapêutico , Administração por Inalação , Adolescente , Adulto , Idoso , Criança , China , Feminino , Humanos , Indonésia , Masculino , Pessoa de Meia-Idade , Filipinas , Modelos de Riscos Proporcionais , República da Coreia , Singapura , Resultado do Tratamento , Adulto JovemRESUMO
This study was performed to use UHPLC-QTOF/MSE technology to rapidly search and identify variations of chemical ingredients between Fructus Schisandrae Chinensis and its processed products. The present study provides a basis for the study of Chinese herbal medicine processing with a focus on the impact of processing on chemical components. Using a time-dependent data scan mode (MSE) couple with metabolomics technology, we acquired accurate data and identified the potential chemical markers. A total of 12 chemical markers were identified in the crude, vinegar-processed and wine-processed Schisandra chinensis fruit; The results showed that the levels of 6-O-benzoylgomisin O, schisantherin B, schisantherin C, schisantherin D and neokadsuranic acid are the highest in crude Schisandra chinensis fruit; thelevels of schizandrin A, schizandrin B, schizandrin C, gomisin D and gomisin T are the highest in wine-processed Schisandra chinensis fruit; the levels of schisantherin A and schisandrin are the highest in vinegar-processed Schisandra chinensis fruit. There were significant changes of chemical components between Fructus Schisandrae Chinensis and their processed products, and these findings may offer a reasonable explanation for variation of efficacy and clinical applications in the processed products of Fructus Schisandrae Chinensis.
Assuntos
Medicamentos de Ervas Chinesas/química , Frutas/química , Schisandra/química , Cromatografia Líquida de Alta Pressão , Ciclo-Octanos , Dioxóis , Lignanas , Metabolômica , Compostos PolicíclicosRESUMO
To study the pharmacokinetics and tissue distribution characteristics of α-hederin sodium salt in rats. 100 mgâ¢kg⻹ α-hederin sodium salt was given to the rats by intragastric administration, and LC-MS/MS method was used to determine its concentration at different time in plasma and tissues. Plasma and tissue samples were treated with methanol protein deposition method. Main pharmacokinetic parameters were as followsï¼ tmax (0.97±1.23) h, Cmax (222.53±57.28) µgâ¢L⻹, AUC0-t (1 262±788.9) h⢵gâ¢L⻹, T1/2 (17.94±9.50) h. α-hederin can be detected in heart, liver, spleen, lung, kidney, brain, muscle and adipose. The results showed that α-hederin sodium salt was absorbed fast and eliminated slowly in rats after oral administration. It was widely distributed in body tissues and livers kept the highest concentrations among various tissues at different time, so it can be speculated that α-hederin may have certain targeting property on livers.
Assuntos
Ácido Oleanólico/análogos & derivados , Saponinas/farmacocinética , Administração Oral , Animais , Fígado/metabolismo , Ácido Oleanólico/farmacocinética , Ratos , Espectrometria de Massas em Tandem , Distribuição TecidualRESUMO
This study is to investigate the indication appropriateness of parenteral nutrition (PN) administration in cancer patients. Between December 2013 and August 2014, all cancer patients who received PN (including total PN and Kabiven) in a regional hospital of Southern Taiwan were included in this retrospective study. A total of 107 cancer patients received PN. Among them, colorectal cancer was the most common type of cancer (n = 45, 42.1%), followed by gastric cancer, head and neck cancer, and esophageal cancer. After evaluation of the appropriateness of PN administration, 88 (82.2%) PN episodes were considered appropriate and unavoidable, 4 (3.7%) as appropriate and avoidable but 15 (14.1%) as inappropriate. In conclusion, PN could be inappropriately used by some oncologic physicians. Physicians and nutrition support team specialists should carefully evaluate the indication of PN administration for cancer patients to obey the generally acknowledged usage rule.
Assuntos
Neoplasias/terapia , Nutrição Parenteral/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , TaiwanRESUMO
Two new compounds 5-[4'-(4â³-hydroxybenzyl)-3'-hydroxybenzyloxymethyl]-furan-2-carbaldehyde (1) and 5-[4'-(4â³-hydroxybenzyl)-3'-hydroxybenzyl]-furan-2-carbal-dehyde (2), together with two known 5-(4-hydroxbenzyloxymethyl)-furan-2-carbaldehyde] (3) and 5-(hydroxymethyl)-2-furaldehyde (4), were isolated from the rhizome of Gastrodia elata. Their structures were elucidated by spectroscopic analysis and comparison of their spectral data with those reported previously. All compounds exhibited weak or no cytotoxicity against human colon carcinoma cell line (HT-29) and human chronic myelogenous leukemia cell line (K-562).
Assuntos
Medicamentos de Ervas Chinesas/isolamento & purificação , Furaldeído/análogos & derivados , Gastrodia/química , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Furaldeído/química , Furaldeído/isolamento & purificação , Furaldeído/farmacologia , Células HT29 , Humanos , Estrutura Molecular , Fenóis/química , Rizoma/químicaRESUMO
OBJECTIVE: To evaluate the application effect of Chinese medical clinical pathway for treating attention-deficit hyperactivity disorder (ADHD), and to provide evidence for further improving clinical pathways. METHODS: Totally 270 ADHD children patients were recruited and treated at pediatrics clinics of 9 cooperative hospitals from December 2011 to December 2012. The treatment course for all was 3 months. Scores of attention deficit and hyperactivity rating scale, scores of behavior, Conners index of hyperactivity (CIH), and Chinese medical syndrome scores were compared between before and after treatment. The efficacy difference in various sexes, ages, and disease courses were evaluated by judging standards for Chinese medical syndrome and ADHD. RESULTS: Fifteen children patients who entered clinical pathway dropped out, and the rest 255 completed this trial. Compared with before treatment, total scores of attention deficit and hyperactivity rating scale, scores of attention deficit and hyperactivity rating scale, CIH, and Chinese medical syndrome scores obviously decreased (all P < 0.01). The total effective rate in disease efficacy was 87.8% (224/255 cases), and the total effective rate in Chinese medical syndrome curative effect was 87.5% (223/255 cases). The clinical curative effect was not influenced by age, gender, or course of disease when statistically analyzed from judging standards for Chinese medical syndrome or for disease efficacy. CONCLUSION: Intervention by Chinese medical clinical pathway could improve ADHD patients' symptoms, and its efficacy was not influenced by sex, age, or course of disease.