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1.
Zhongguo Zhong Yao Za Zhi ; 47(8): 1995-2007, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35531714

RESUMO

Quality evaluation of Chinese medicinal decoction pieces is vital for the development of the downstream industries, and is an important channel for implementing the strategy of "higher quality, higher price, and priority for the high quality" for traditional Chinese medicine. At the moment, the quality of Chinese medicinal decoction pieces is mainly evaluated based on chemical component examination. Considering the weak preliminary research foundation and poor research conditions, traditional experience-based evaluation is undervalued in the quality rating of Chinese medicinal decoction pieces. However, traditional experience is a summary of the quality of Chinese medicinal materials based on clinical experience, which thus can be a potential basis for the quality evaluation of the decoction pieces. It is a challenge in the evaluation of Chinese medicinal decoction pieces to objectify the traditional experience-based evaluation from multiple aspects such as chemistry, effect, and characterization via modern techniques. Therefore, this study developed the "experience-ingredients-activity-electronic sensing" evaluation system for Chinese medicinal decoction pieces on the basis of experience-based assessment, chemical ingredients that can truly reflect the traditional experience, biological effect assessment, and electronic sensory evaluation, which is expected to quantify the traditional experience of quality evaluation of Chinese medicinal decoction pieces via chemistry, biology, and sensory simulation. The evaluation system can serve as a reference for clinical experience-based quality evaluation of Chinese medicinal decoction pieces.


Assuntos
Medicamentos de Ervas Chinesas , China , Eletrônica , Medicina Tradicional Chinesa , Restrição Física
2.
Zhongguo Zhong Yao Za Zhi ; 46(23): 6163-6177, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34951243

RESUMO

This study aimed to qualitatively analyze the chemical components in Xiaoer Chiqiao Qingre Granules(XRCQ) by UHPLC-LTQ-Orbitrap-MS/MS and identify its material basis. The absorbed components in plasma were combined for exploring the potential action mechanism by integrated network pharmacology. ACQUITY UPLC HSS T3(2.1 mm×100 mm, 1.8 µm) column and mobile phase system of 0.1% formic acid solution(A)-acetonitrile(B) were used for gradient elution, followed by high resolution liquid chromatography-mass spectrometry in both positive and negative ion scanning modes. According to the precise relative molecular mass and MS/MS fragment ions, a total of 124 chemical components were identified in XRCQ by the comparison with references and literature reports, among which 29 compounds were completely confirmed by comparison with reference substances. Then, the main absorbed components of XRCQ in plasma were also analyzed and clarified by UHPLC-LTQ-Orbitrap-MS/MS. BATMAN-TCM and SwissTargetPrediction were used for target prediction of absorbed components in plasma. Following the plotting of association network with Cytoscape 3.8.2, the core targets were subjected to GO and KEGG pathway enrichment analysis and a component-target-pathway network was constructed. A total of eight main targets of XRCQ against fever in children were obtained together with eight absorbed components in plasma, including glycyrhydinic acid, hesperidin, emodin, reticuline, daidzein, magnolignan C, magnolignan A, and magnolaldehyde D. It was inferred that XRCQ might improve alimentary system abnormality, inflammatory response, oxidative stress, and endocrine disorder through tumor necrosis factor, PI3 K-AKT, and other signaling pathways. The present study comprehensively expounded the chemical profiles of XRCQ and the main absorbed components in plasma and predicted the potential mechanism of XRCQ based on integrated network pharmacology, which has provided certain theoretical reference for the clinical application of XRCQ.


Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Criança , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Humanos
3.
Zhongguo Zhong Yao Za Zhi ; 46(18): 4774-4781, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34581088

RESUMO

Indolealkylamines(IAAs) are the main hydrophilic substances in toad skin, mainly including free N-methyl-5-hydroxytryptamine, bufotenine, bufotenidine, dehydrobufotenine, and binding bufothionine. In this study, the LPS-activated neutrophils were used to investigate the structure-activity relationship and anti-inflammatory mechanism of the above-mentioned five monomers from the toad skin in vitro. The neutrophils were divided into the control group, model group(1 µg·mL~(-1) LPS), positive drug group(100 µg·mL~(-1) indometacin), as well as the low-(50 µg·mL~(-1)), medium-(100 µg·mL~(-1)) and high-dose(200 µg·mL~(-1)) free N-methyl-5-hydroxytryptamine, bufotenine, bufotenidine, dehydrobufotenine, and binding bufothionine groups. The levels of IL-6, TNF-α and IL-1ß in the neutrophil supernatant of each group was measured by enzyme-linked immunosorbent assay(ELISA) after LPS stimulation, followed by the detection of apoptosis in each group after Annexin V/PI staining. The protein expression levels of caspase-3, Bax, Bcl-2, beclin1, LC3-I, and LC3-Ⅱ were assayed by Western blot. The results showed that IAAs reduced the excessive secretion of inflammatory cytokines caused by LPS compared with the model group. Besides, the activity of each free IAAs(N-methyl-5-hydroxytryptamine, bufotenine, bufotenidine and dehydrobufotenine), especially bufotenine, was stronger than that of the binding bufothionine. As revealed by Annexin V/PI staining, LPS delayed the early apoptosis of neutrophils compared with the control group, while bufotenine promoted the apoptosis of neutrophils in a dose-dependent manner, which might be related to the elevated expression of apoptosis-related protein Bax/Bcl-2. In addition, LPS activated the autophagy pathways in neutrophils. This study confirmed the efficacy of IAAs in reducing the secretion of inflammatory cytokines in neutrophils induced by LPS for the first time. For instance, bufotenine exerts the anti-inflammatory effect possibly by inducing the apoptosis of neutrophils.


Assuntos
Lipopolissacarídeos , Neutrófilos , Animais , Anti-Inflamatórios/farmacologia , Apoptose , Bufonidae , Lipopolissacarídeos/toxicidade , Pele
4.
Zhongguo Zhong Yao Za Zhi ; 46(1): 171-176, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33645067

RESUMO

The aim of this paper was to study the effect and mechanism of fucoxanthin on insulin resistance of obese mice induced by high-fat diet. Fifty C57 BL/6 J male mice were randomly divided into control group and high-fat diet group. The insulin resistance model was induced with high-fat diet for 12 weeks, and model mice were randomly divided into model group, fucoxanthin-0.2% group, fucoxanthin-0.4% group and metformin group. After dietary treatment for 6 weeks, the body weight and epididymal fat weight in each group were measured. Fasting blood glucose(FBG), fasting insulin(FINS), total cholesterol(TC), triglyceride(TG), low-density lipoprotein(LDL-C) and high-density lipoprotein(HDL-C) were measured, and insulin resistance index(HOMA-IR) was calcula-ted. The pathological morphology in liver was observed by hematoxylin eosin staining, and the expressions of some key proteins in insulin receptor substrate 1(IRS-1)/posphoinositide 3-kinase(PI3 K)/serine-threonine kinase(Akt) and peroxisome proliferators-activated receptor-γ(PPARγ)/sterol regulatory element binding protein-1(SREBP-1)/fatty acid synthetase(FAS) pathways in liver were detected by Western blot. According to the findings, compared with the model group, levels of body weight, epididymal fat weight, FBG, FINS, TC, TG, LDL-C and HOMA-IR, as well as protein expressions of PPARγ, SREBP-1 and FAS in liver were significantly reduced(P<0.05 or P<0.01), while level of HDL-C and protein expressions of p-IRS-1, IRS-1, PI3 K and p-Akt in liver were signi-ficantly increased after treatment with fucoxanthin(P<0.05 or P<0.01). And the pathological changes of liver tissue in fucoxanthin-treated mice were also improved obviously. The results showed that fucoxanthin could improve obesity, hyperglycemia and hyperlipidemia, and alleviate insulin resistance in obese mice, and its mechanism is possibly related to the regulation of IRS-1/PI3 K/Akt and PPARγ/SREBP-1/FAS pathways.


Assuntos
Resistência à Insulina , Animais , Dieta Hiperlipídica/efeitos adversos , Insulina , Fígado , Masculino , Camundongos , Camundongos Obesos , Xantofilas
5.
J Ethnopharmacol ; 272: 113917, 2021 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-33609729

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Qingxin Lianzi Yin Decoction (QXLZY), a Chinese classical formula, has been widely used in the treatment of various chronic kidney diseases over 1,000 years. However, the current studies on QXLZY were mostly focused on its clinical efficacy, lacking systematic material basis research on constituents. AIM OF THE STUDY: This work aims to elucidate and quantify the chemical constituents, clarify the blood-absorbed components and excretion pathways, predict major bioactive constituents and discover potential therapeutic targets. MATERIALS AND METHODS: UHPLC-LTQ-Orbitrap HRMS was employed to clarify the chemical constituents and metabolites of QXLZY. The extraction of diagnostic ion and neutral loss fragment was aimed for searching specific type of constituents. The plasma, urine, bile and feces samples of rats after oral administration of QXLZY were systematically studied. UHPLC-QQQ-MS/MS was employed to simultaneously detect different types of constitutes. Based on the analysis of ingredients in vivo, the bioactive constituents and potential therapeutic targets in the treatment of diabetic nephropathy (DN) was investigated by using network pharmacological analysis. RESULTS: Totally, 220 compounds were identified or tentatively characterized by UHPLC-LTQ-Orbitrap HRMS. Among them, 59 compounds were confirmed by reference standards. Meanwhile, 21 representative components were simultaneously determined within 15 min by UHPLC-QQQ-MS/MS. 123 components (74 prototypes as well as 49 metabolites) were identified or tentatively characterized. By using network pharmacological analysis, baicalein, liquiritigenin, succinic acid, formononetin, wogonin might be the major effective constituents in QXLZY during the treatment of DN. CONCLUSIONS: Flavonoids, saponins and organic acids were the major chemical ingredients of QXLZY. Flavonoids were the main components absorbed into blood, followed by organic acids. Phase II conjugation reaction was the major metabolic type. The pathways that QXLZY in the treatment of DN were probably related to glucose and lipid metabolism, oxidative stress and inflammation.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Ácidos/análise , Alcaloides/análise , Animais , Cromatografia Líquida de Alta Pressão , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/análise , Flavonoides/análise , Masculino , Metaboloma , Compostos Fitoquímicos/administração & dosagem , Compostos Fitoquímicos/análise , Mapas de Interação de Proteínas , Ratos Sprague-Dawley , Padrões de Referência , Reprodutibilidade dos Testes , Saponinas/análise , Espectrometria de Massas em Tandem
6.
Zhongguo Zhong Yao Za Zhi ; 45(13): 3035-3044, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32726009

RESUMO

UHPLC-LTQ-Orbitrap-MS was developed for the identification of chemical constituents in Qingfei Paidu Decoction, which will clarify its material basis. ACQUITY UHPLC HSS T3 chromatography column(2.1 mm×100 mm, 1.8 µm) was used with 0.1% formic acid(B)-acetonitrile(A) as the mobile phase in gradient elution. The decoction was detected by high-resolution liquid chromatography-mass spectrometry equipped with an ESI ion source in positive and negative mode. Based on the accurate mass measurements, retention time, mass fragmentation patterns combined with comparison of reference and literature reports, a total of 87 major compounds including 43 flavonoids, 9 alkaloids, 4 triterpenoid saponins, 1 sesquiterpene, 2 coumarins, 10 phenolic acids and 18 other compounds were tentatively screened and characterized. UHPLC-LTQ-Orbitrap-MS was employed to comprehensively elucidate the chemical components in Qingfei Paidu Decoction, which basically covered 20 Chinese medicines except gypsum in Qingfei Paidu Decoction. These collective results provide a scientific basis for further research on the quality control standard of Qingfei Paidu Decoction.


Assuntos
Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão , Cumarínicos/análise , Flavonoides/análise , Espectrometria de Massas
7.
Zhongguo Zhong Yao Za Zhi ; 45(7): 1488-1498, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32489025

RESUMO

Coronavirus disease 2019(COVID-19) has attracted great attentions from the whole world. Traditional Chinese medicine(TCM) has been widely used and shown satisfying efficacies in treating all stages of COVID-19. In this study, the molecular interaction networks of different stages of COVID-19(the early, severe, critical and recovery stage) were constructed using the links among symptoms-related genes collected from TCMIP V2.0(http://www.tcmip.cn/), an integrated pharmacology network-computing platform for TCM. Following the network topological feature calculation and functional enrichment analysis, we found that the molecular targets and pathways related with the "immune-inflammation system" were involved throughout all the stages of COVID-19. The severe stage and the critical period of COVID-19 were occupied by a large proportion of inflammatory factors and pathways, suggesting that there might be a cytokine storm in these periods, along with respiratory disorders, cardiopulmonary dysfunction, nervous system disorders, etc. Accordingly, the therapeutic targets and pathways hit by the recommended prescriptions against COVID-19 were also aimed to regulate the balance of immune-inflammation system, nutrient absorption and metabolism, abnormal energy metabolism, the cardio-pulmonary function, nerve system function, etc., which may be related to the therapeutic effects of these prescriptions in terms of several clinical symptoms, such as expiratory dyspnea, chest tightness and shortness of breath, abdominal distension and constipation, sweating and limb cold, dizziness, and irritability, etc. The above findings reflect the integrative actions of TCM characterizing by multiple-components, multiple-targets, multiple-pathways, and multiple-effects. This study systematically constructed the molecular networks of different TCM syndromes during the development and progression of COVID-19 and uncovered the biological basis for symptomatic treatment of TCM. Furthermore, our data revealed the pharmacological mechanisms and the scientific connotation of recommended prescriptions, which may provide supports for the prevention and treatment of COVID-19 using TCM.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Medicamentos de Ervas Chinesas , Pandemias , Pneumonia Viral , COVID-19 , Infecções por Coronavirus/tratamento farmacológico , Humanos , Medicina Tradicional Chinesa , Pneumonia Viral/tratamento farmacológico , SARS-CoV-2
8.
Zhongguo Zhong Yao Za Zhi ; 45(9): 2203-2209, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32495572

RESUMO

To systematically review the effectiveness and safety of Pudilan Xiaoyan Oral Liquid on child upper respiratory infection and conduct Meta-analysis. We electronically retrieved databases, including PubMed, Web of Science, VIP, WanFang and CNKI, for published articles of randomized controlled trials(RCTs) of Pudilan Xiaoyan Oral Liquid on child upper respiratory infection from inception to April 2019. According to the inclusion and exclusion criteria, two reviewers independently screened out literatures, extracted data and assessed the risk of bias in included studies. Then, Meta-analysis were conducted by Stata 15.0 software. A total of 16 RCTs involving 1 924 patients with upper respiratory infection were included. The results of Meta-analysis showed that the improvement of clinical symptoms, such as fever subsided time(WMD=-3.66, 95%CI[-4.61,-2.72], P<0.001), cough time(WMD=-1.89, 95%CI[-2.51,-1.27], P<0.001), time of runny noses(WMD=-4.60, 95%CI[-5.85,-3.34], P<0.001) and time of sore throat(WMD=-2.62, 95%CI[-3.54,-1.70], P<0.001). Meanwhile, the results of Meta-analysis showed the improvement of laboratory indications, including TNF-α(WMD=-2.68, 95%CI[-2.98,-1.58], P<0.001) and IL-6(WMD=-2.26, 95%CI[-3.36,-2.36], P<0.01). The current evidence shows that Pudilan Xiaoyan Oral Liquid may significantly improve the effectiveness and safety. According to the limited quality of included studies, the above conclusion needs be to verified with more high-quality studies.


Assuntos
Medicamentos de Ervas Chinesas , Faringite , Criança , Humanos , Fator de Necrose Tumoral alfa
9.
J Ethnopharmacol ; 260: 112943, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-32422359

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Arenobufagin (ArBu) is an important anti-tumor ingredient of Chan'su which has long been used as traditional Chinese medicine in clinic for tumor therapy in China. AIM OF THE STUDY: The purpose of our study is to investigate the lipid homeostasis regulation effects of ArBu on zebrafish model of liver cancer and hepatoma cells, and to provide a reference for further clarifying its active mechanisms. MATERIALS AND METHODS: The zebrafish xenograft model was established by injecting HepG2 cells stained with CM-Dil red fluorescent dye. Both the xenograft model and HepG2 cells were used to evaluate the anti-hepatoma activity of ArBu. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was the main method to study lipidomics, proteomics and the semiquantification of endogenous metabolites. Bioinformatics was used as an assistant tool to further explore the antitumor mechanism of ArBu. RESULTS: The lipidomics analysis revealed that ArBu caused differential lipids changes in a dose-dependent manner, including PCs, PEs, TGs, SMs, DGs, Cer and PA. PCs, PEs, SMs and TGs were markedly altered in both two models. The influence of glycerophospholipid metabolism was the major and commonly affected pathway. Notably, DGs and Cer were significantly changed only in HepG2 cells. Furthermore, the proteomics research in HepG2 cells fished the target proteins related to lipid homeostasis abnormalities and tumor suppression. ArBu reduced the expression of 65 differential proteins associated with the lipid metabolism, apoptosis and autophagy, such as LCLAT1, STAT3, TSPO and RPS27. Meanwhile, 7 amino acids of 29 determined metabolites were significantly changed, including tyrosine, glutamate, glutamine, leucine, threonine, arginine and isoleucine. CONCLUSION: ArBu has a significant anti-hepatoma effect in vitro and a therapeutic effect on zebrafish xenograft model. It regulated the lipid homeostasis. Activated SM synthase and arginine deiminase, inhibited sphingomyelinase, amino acid supply and JAK-STAT3 signaling pathway, and the affected glycerophospholipid metabolism might explain these results.


Assuntos
Antineoplásicos/farmacologia , Bufanolídeos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipidômica , Neoplasias Hepáticas/tratamento farmacológico , Proteômica , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Autofagia/efeitos dos fármacos , Proteínas Relacionadas à Autofagia/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Metabolismo dos Lipídeos/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Mapas de Interação de Proteínas , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-Zebra
10.
Zhongguo Zhong Yao Za Zhi ; 45(5): 1082-1089, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32237450

RESUMO

Some Chinese herbal medicine needs to be processed before it can be used as medicine, especially toxic Chinese medicine. Highly toxic Aconti Kusnezoffii Radix(Caowu in Chinese) is widely used in traditional Chinese medicine and Mongolian medicine. In traditional Chinese medicine, Caowu is usually processed by boiling with water(CW) until no white part inside and being tasted without tongue-numbing. In Mongolian medicine, it is usually soaked in Chebulae Fructus(Hezi in Chinese) decoction for several days(CH). Both methods could reduce toxicity according to reports. The biggest difference between CW and CH is that CW needs to be heated for 4-6 h, while CH needs Hezi as processing adjuvants. To explore the toxicity reduction mechanism of CW and CH, we studied the contents of various compounds in Caowu processed by two methods by UPLC-Orbitrap-MS. The results indicated that CW had 14 new ingredients, such as 14-O-anisoylneoline and dehydro-mesaconitine, while N-demethyl-mesaconitine and aconitine disappeared. At the same time, it could significantly decrease the content of diester diterpenoid alkaloids and increase the contents of monoester diterpenoid alkaloids and amine-diterpenoid alkaloids. CH had 9 new ingredients from Hezi, like gallic acid, chebulic acid and shikimic acid. Neither the kinds nor the contents of compositions from Caowu in CH changed little. This suggested that the processing mechanism of CW reduced highly toxic components(diester diterpenoid alkaloids) and increased the content of lowly toxic components(monoester diterpenoid alkaloids and amine-diterpenoid alkaloids). Attenuated principle of CH may be related to the components of Hezi. In this experiment, the conclusion shows that the chemical constituents of CW and CH are essentially different, and the two methods have different toxicity reduction principles.


Assuntos
Aconitum/química , Alcaloides/análise , Medicamentos de Ervas Chinesas/análise , Aconitina , Química Farmacêutica/métodos , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Medicina Tradicional Chinesa
11.
Zhongguo Zhong Yao Za Zhi ; 45(3): 596-601, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32237518

RESUMO

Matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI) is a novel technique for in-situ distribution of various substances in tissue without labeling. This technique is increasingly applied to the study of medicinal plants owing to its high spatial resolution and its potential of in-situ analysis in small molecules. In this study, the structural information and their fragmentation patterns of the midazole alkaloids(1,3-dibenzyl-4,5-dimethylimidazolium chloride and 1,3-dibenzyl-2,4,5-trimethylimi-dazolium chloride) and benzylglucosinolate in the medicinal plant Maca(Lepdium meyeni) root were analyzed by ultra-high-performance liquid phase combined with LTQ-Orbitrap mass spectrometry(UHPLC-HR-MS). The localization of these active ingredients in the cross-sections of Maca root was performed by MALDI-MSI. These results demonstrated that the two types of imidazole alkaloids had a similar distributed pattern. They were located more in the cortex and the periderm than those in the medulla of a lateral root, while the localization of benzylglucosinolate was concentrated in the center of the root rather than in the cortex and the periderm. The precise spatial distribution of various secondary metabolites in tissue provides an important scientific basis for the accumulation of medicinal plant active ingredients in tissues. In addition, this imaging method is a promising technique for the rapid evaluation and identification of the active ingredients of traditional Chinese medicine in plant tissues, as well as assisting the research on the processing of medicinal plants.


Assuntos
Lepidium/química , Compostos Fitoquímicos/análise , Raízes de Plantas/química , Cromatografia Líquida de Alta Pressão , Plantas Medicinais/química , Metabolismo Secundário , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
12.
Zhongguo Zhong Yao Za Zhi ; 44(22): 4932-4939, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31872603

RESUMO

This study is aimed to establish a method for the determination of baicalin,baicalin and purpurin in the plasma of rats after oral administration of Pudilan Xiaoyan Oral Liquid( PDL) by using liquid chromatography-mass spectrometry( LC-MS),analyze the pharmacokinetics of three components in rats,and investigate the effects of PDL on drug-metabolizing enzymes in rat liver. C18 column was used for liquid chromatography separation,with acetonitrile-water( containing 0. 2% formic acid) as the mobile phase for gradient elution. The mass spectrometry was detected by electrospray ion source( ESI) under multi-reaction monitoring mode( MRM),as well as positive and negative ion alternating mode. Plasma sample collection was performed by using an automatic blood collection meter for small animals. The pharmacokinetic parameters were calculated by Win Nonlin software. The total protein concentration of rat liver microsomes and the total enzyme content of CYP450 were determined by BCA method and spectrophotometry respectively. The methodological study in terms of linear range,recovery rate,precision and sample stability,was used to confirm that the LC-MS analysis method established in this experiment was simple,exclusive,accurate and reliable,and can meet the requirement of determining the content of baicalin,oroxindin and corynoline in plasma after PDL administration in rats. The drug-time curve showed that baicalin and oroxindin had a bimodal phenomenon,and the pharmacokinetic parameters indicated that baicalin,oroxindin and corynoline in PDL had certain drug-like properties. After 7 consecutive days of PDL administration,the rat liver coefficient,total liver microparticle protein and CYP450 enzyme content were increased,but there was no significant difference,indicating that PDL was less likely to develop drug-drug interaction based on CYP enzyme. The results of this experiment can provide reference for the research on in vivo efficacy and drug interaction of PDL as well as on its clinical application.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Espectrometria de Massas em Tandem , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Fígado , Ratos , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray
13.
Zhongguo Zhong Yao Za Zhi ; 44(8): 1573-1587, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-31090321

RESUMO

UPLC-ESI-Orbitrap-MS/MS was used to analyze,identify and attribute the chemical constituents in Pudilan Antiphlogistic Oral Liquid. The analysis was performed on an Agilent Eclipse XDB-C18(4.6 mm × 150 mm,3.5 µm) with a gradient mobile phase of methanol-0.1% formic solution system at the flow rate of 0.5 m L·min-1. The sample volume was 2 µL. The column temperature was30 ℃. The high-resolution orbitrap mass spectrometry was used as detector,with electrospray ion source in both positive and negative models,and the MS scanning ranged between m/z 50 and 2 000. Based on the analysis of mass spectrometry and literature reports,79 compounds were confirmed,including 30 alkaloids,28 organic acids,18 flavonoids and 3 coumarins. Finally,39 compounds,such as rutin,esculetin,gallic acid,caffeic acid,cichoric acid,were identified from Taraxacum mongolicum; 11 compounds,such as baicalin,baicalein,apigenin,chrysin,oroxylin A,were identified from Scutellaria baicalensis; 13 compounds,such as arginine,proline,hypoxanthine,epigoitrin,indirubin,were identified from Isatis indigotica; and 18 compounds,such as dehydrocheilanthifoline,oxysanguinarine,corynoline,protopine,spallidamine,were identified from Corydalis bungeana. After the analysis of chemical model and attribution,the contents of some compounds were high in Pudilan Antiphlogistic Oral Liquid,such as baicalin,wogonoside,baicalein,wogonin,apigenin,chrysin,skullcapflavonⅡ,oroxylin A,cichoric acid,chlorogenic acid,caffeic acid,esculetin,dehydrocheilanthifoline,dihydrosanguinarine,protopine,corynoline and indirubin. The established method is simple,accurate,rapid,sensitive and reproducible,and thus suitable for the qualitative identification and quantitative determination of Pudilan Antiphlogistic Oral Liquid,which lays a foundation for the systematic quality control and the establishment of whole-course traceability system of active ingredients.


Assuntos
Anti-Inflamatórios/análise , Medicamentos de Ervas Chinesas/química , Compostos Fitoquímicos/análise , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas em Tandem
14.
Zhongguo Zhong Yao Za Zhi ; 44(1): 158-166, 2019 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-30868827

RESUMO

In order to find the endogenous potential biomarkers of in vitro hepatic injury caused by NCTD-Na and elucidate the mechanism of hepatic injury of NCTD-Na,ultra-high performance liquid chromatography coupled quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was used for lipidomics detection.Multivariate statistical analysis was used to study the endogenous lipid metabolic changes of human normal liver cells LO2 injury after the treatment with sodium norcantharidate(NCTD-Na).The results showed that the half maximal inhibitory concentration(IC50) of NCTD-Na was 0.034 mmol·L-1.A total of 280 differential metabolites were found between the control group and the low-dose group,with VIP > 2.0 and P<0.05.At the same time,a total of 273 differential metabolites were found between the control group and the high-dose group,with VIP > 2.0 and P<0.05.Cell metabolite profiles showed clear separation among control group,the low-dose group and the high-dose group,and 111 differential metabolites were found,with VIP > 2.0,P<0.05,RSD<30% and in a dose-dependent manner.It was found that most of the above differential metabolites were lipid metabolites after the analysis of simple preparnation methods and database search.A total of 32 potential biomarkers were identified,including 3 phosphatidylcholine(PC),5 lysophosphatidylcholine(Lyso PC),3 ceramide(Cer),1 sphingomyelin(SM),1 phosphatidylethanolamine(PE),10 lysophosphatidylethanolamine(LysoPE),4 diacylglycerol(DG),1 Phosphatidic acid(PA),1 lysophosphatidic acid(Lyso PA),1 phosphatidyl glycerol(PG),1 fatty acid hydroxy fatty acid(FAHFA) and 1 phosphatidylserine(PS).The changes of PCs,Cers,SM,PE and DGs were closely related liver protection,DNA methylation and self-repair in hepatocytes,apoptosis,methylation and detoxification of carcinogens,as well as lipid peroxides production process.Also,they had impact on the proliferation of hepatocytes,differentiation and gene transcription disorders.Cells stimulated by NCTD-Na could promote the production of PA as well as the synthesis and catabolism of FAHFA in a variety of ways.The levels of Lyso PCs,LysoPEs and Lyso PA were correlated with PCs,PE and PA;PE and PS might have valgus during apoptosis,triggering phagocytosis.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Hepatócitos/efeitos dos fármacos , Metabolismo dos Lipídeos , Células Cultivadas , Hepatócitos/metabolismo , Humanos , Lipídeos/análise , Espectrometria de Massas em Tandem
16.
Int J Oncol ; 53(6): 2488-2502, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30272276

RESUMO

Glioblastoma is the most common and lethal intracranial tumor type, characterized by high angiogenic and infiltrative capacities. To provide a novel insight into therapeutic strategies against glioblastoma, the cytotoxicity of arenobufagin and hellebrigenin was investigated in the human glioblastoma cell line, U-87. Similar dose-dependent cytotoxicity was observed in the cells, whereas no detectable toxicity was confirmed in mouse primary astrocytes. Treatment with each drug downregulated the expression levels of Cdc25C, Cyclin B1 and survivin, which occurred in parallel with G2/M phase arrest. Necrotic-like cell death was only observed in the cells treated with a relatively high concentration (>100 ng/ml). These results indicate that the two drugs exhibited distinct cytotoxicity against cancerous glial cells with high potency and selectivity, suggesting that growth inhibition associated with G2/M phase arrest and/or necrosis were attributed to their toxicities. Activation of the p38 mitogen activated protein kinase (MAPK) signaling pathway was also observed in treated cells. Notably, a specific inhibitor of p38 MAPK, SB203580, itself caused a significant decrease in cell viability, and further enhanced the cytotoxicity of the two drugs, suggesting an important pro-survival role for p38 MAPK. Given that p38 MAPK serves an essential role in promoting glioblastoma cell survival, developing a novel combination regimen of arenobufagin/hellebrigenin plus a p38 MAPK inhibitor may improve the efficacy of the two drugs, and may provide more therapeutic benefits to patients with glioblastoma. The qualitative assessment demonstrated the existence of arenobufagin in the cerebrospinal fluid of arenobufagin-treated rats, supporting its clinical application.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Encefálicas/metabolismo , Bufanolídeos/farmacologia , Ciclo Celular/efeitos dos fármacos , Glioblastoma/metabolismo , Animais , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ciclina B1/genética , Ciclina B1/metabolismo , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Humanos , Imidazóis/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Piridinas/farmacologia , Ratos , Survivina/genética , Survivina/metabolismo , Fosfatases cdc25/genética , Fosfatases cdc25/metabolismo
17.
Zhongguo Zhong Yao Za Zhi ; 43(14): 3006-3011, 2018 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-30111062

RESUMO

To study the pharmacokinetics of active ingredients (alkaloids, iridoids and flavonoids) in Huanglian Jiedu decoction (HLJDD) in Alzheimer's disease (AD) model rats, and investigate its mechanism in treatment of AD. All of rats were divided into normal control group (n=6), shame operation group (n=6) and model group (n=12). Rats in shame operation group received daily subcutaneous injection of D-galactose (D-gal 50 mg·kg⁻¹) for a total of 45 d to induce subacute aging model. Based on the operation of shame operation group, the rats in model group were given with an injection of Aß25₋35 (4.0 g·L⁻¹)-ibotenic acid (2.0 g·L⁻¹) into the nucleus basalis magnocellularis. Then rats in model group were divided into HLJDD one day administration group (n=6) and HLJDD one week group (n=6). The plasma concentration of alkaloids, iridoid and flavonoids was determined by liquid chromatography tandem mass spectrometry (LC-QQQ-MS) at different time points. The levels of seven inflammatory factors (MIP-2, IL-1ß, IL-2, IL-8, IL-10, IL-13, TNF-α) in cerebrospinalfluid (CSF) were measured by Bio-Plex multi-factor detection technology. Iridoids in AD model rats, with high bioavailability, were easily absorbed and eliminated. The plasma concentration of alkaloid was lower, and the AUC (area under the curve) was higher in HLJDD one week group than that in HLJDD one day group. The plasma concentration-time curves of flavonoids showed obvious bimodal phenomena. After the gastric administration of HLJDD, the inflammatory factors in CSF of AD rats demonstrated a callback trend, including IL-1ß/IL-10 (P<0.05) with significant difference. The pharmacokinetic behaviors of iridoids, alkaloids and flavonoids (41 compounds) in AD model rats were fundamentally elucidated, and HLJDD can improve the central inflammatory status of AD rats by regulating the levels of inflammatory factors.


Assuntos
Doença de Alzheimer , Medicamentos de Ervas Chinesas , Animais , Encéfalo , Inflamação , Ratos , Ratos Sprague-Dawley
18.
Tissue Cell ; 52: 1-8, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29857817

RESUMO

Sirtuin 3 (SIRT3) mediates cellular resistance toward various forms of stress. SIRT3 expression in the developing brain, especially its localization in various glial cell types, has not been fully explored. This study aimed to determine SIRT3 expression in the brain of neonatal rats subjected to hypoxia. By immunohistochemistry, immunofluorescence and Western blotting, we show here that SIRT3 expression in the periventricular white matter was up-regulated in hypoxia group compared with the control group at the corresponding time points. Intense SIRT3 expression was detected in microglia at early time points after hypoxia whose cell number was increased with reduced ramifications in hypoxia group compared with the control group. Furthermore, SIRT3 immunoreactivity was obviously enhanced at 24 h, 3 and 7d, but was declined at 14d after hypoxia so that SIRT3 expression between the two groups was comparable. SIRT3 immunofluorescence was also localized in astrocytes labeled with GFAP which was augmented at different time points in hypoxia group. GPAP positive astrocytes exhibited long extending processes being most pronounced at 3d. SIRT3 was moderately expressed at 24 h, 3 and 7d, but was markedly increased at 14d after hypoxia. Moderate SIRT3 expression was also localized in oligodendrocytes labeled with CNPase in the control group. The incidence of CNPase positive oligodendrocytes showing colocalization of SIRT3 increased significantly at 24 h, 3 and 7d after hypoxia. In conclusion, SIRT3 expression was differentially up-regulated in all three major glial cell types following hypoxia. It is suggested that increased SIRT3 expression in the respective glial cell types following hypoxia is involved in different signaling pathways that protect against hypoxic stress in the developing brain.


Assuntos
Encéfalo/metabolismo , Hipóxia/metabolismo , Neuroglia/metabolismo , Sirtuínas/biossíntese , Substância Branca/metabolismo , Animais , Animais Recém-Nascidos , Feminino , Masculino , Ratos , Ratos Sprague-Dawley
19.
J Agric Food Chem ; 66(11): 2917-2924, 2018 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-29504397

RESUMO

Formononetin and its glycoside ononin are bioactive isoflavones widely present in legumes. The present study investigated the pharmacokinetics, bioavailability, and in vitro absorption of formononetin and ononin. After an oral administration to rats, formononetin showed a higher systemic exposure over ononin. The oral bioavailability of formononetin and ononin were 21.8% and 7.3%, respectively. Ononin was more bioavailable than perceived, and its bioavailability reached 21.7% when its metabolite formononetin was taken into account. Both formononetin and ononin exhibited better absorption in large intestine segments than that in small intestine segments. Formononetin displayed a better permeability in all intestinal segments over ononin. Transport of formononetin across Caco-2 cell monolayer was mainly through passive diffusion, while ononin was actively pumped out by MRP2 but not P-gp. The results provide evidence for better understanding of the pharmacological actions of formononetin and ononin, which advocates more in vivo evaluations or human trials.


Assuntos
Glucosídeos/farmacocinética , Isoflavonas/farmacocinética , Extratos Vegetais/farmacocinética , Animais , Disponibilidade Biológica , Transporte Biológico , Células CACO-2 , Humanos , Absorção Intestinal , Mucosa Intestinal/metabolismo , Intestinos/química , Masculino , Modelos Biológicos , Permeabilidade , Ratos , Ratos Sprague-Dawley
20.
Zhongguo Zhong Yao Za Zhi ; 42(8): 1532-1538, 2017 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-29071858

RESUMO

Biopharmaceutics classification system of Chinese materia medica (CMMBCS) emphasizes characteristic of the multi-component environment based on the drug solubility and permeability. In this study, the in situ closed-loop method combined with LC-MS technique was utilized to study the intestinal absorption and metabolism of Puerariae Lobatae Radix decoction (PLRD), providing selection basis for intestinal permeability components in CMMBCS. A total of 36 components were identified from PLRD. Among them, 17 components could be detected in the plasma sample, indicating that 17 components could be absorbed into blood, so these 17 components could be used as intestinal permeability evaluation components in CMMBCS. The other 19 components were not detected in the plasma sample, suggesting that they may not be absorbed or metabolized by the gut wall enzymes.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Absorção Intestinal , Pueraria/química , Humanos , Raízes de Plantas/química
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