RESUMO
Ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry(UHPLC-Q-TOF-MS) was employed in this study to observe the effect of Huaihua Powder on the serum metabolites of mice with ulcerative colitis and reveal the mechanism of Huaihua Powder in the treatment of ulcerative colitis. The mouse model of ulcerative colitis was established by dextran sodium sulfate salt(DSS). The therapeutic effect of Huaihua Powder on ulcerative colitis was preliminarily evaluated based on the disease activity index(DAI), colon appearance, colon tissue morphology, and the content of inflammatory cytokines such as tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1ß(IL-1ß). UHPLC-Q-TOF-MS was employed to profile the endogenous metabolites of serum samples in blank control group, model group, and low-, medium-, and high-dose Huaihua Powder groups. Multivariate analyses such as principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were performed for pattern recognition. Potential biomarkers were screened by Mass Profiler Professional(MPP) B.14.00 with the thresholds of fold change≥2 and P<0.05. The metabolic pathways were enriched by MetaboAnalyst 5.0. The results showed that Huaihua Powder significantly improved the general state and colon tissue morphology of mice with ulcerative colitis, reduced DAI, and lowered the levels of TNF-α, IL-6, and IL-1ß in serum. A total of 38 potential biomarkers were predicted to be related to the regulatory effect of Huaihua Powder, which were mainly involved in glycerophospholipid metabolism, glycine, serine, and threonine metabolism, mutual transformation of glucuronic acid, and glutathione metabolism. This study employed metabolomics to analyze the mechanism of Huaihua Powder in the treatment of ulcerative colitis, laying a foundation for the further research.
Assuntos
Colite Ulcerativa , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Pós , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Metabolômica , Colo , Modelos Animais de Doenças , Biomarcadores , Sulfato de Dextrana/metabolismo , Sulfato de Dextrana/farmacologia , Sulfato de Dextrana/uso terapêuticoRESUMO
Obesity, which has unknown pathogenesis, can increase the frequency and seriousness of acute myocardial infarction (AMI). This study evaluated effect of Huayu Qutan Recipe (HQR) pretreatment on myocardial apoptosis induced by AMI by regulating mitochondrial function via PI3K/Akt/Bad pathway in rats with obesity. For in vivo experiments, 60 male rats were randomly divided into 6 groups: sham group, AMI group, AMI (obese) group, 4.5, 9.0 and 18.0 g/kg/d HQR groups. The models fed on HQR with different concentrations for 2 weeks before AMI. For in vitro experiments, the cardiomyocytes line (H9c2) was used. Cells were pretreated with palmitic acid (PA) for 24 h, then to build hypoxia model followed by HQR-containing serum for 24 h. Related indicators were also detected. In vivo, HQR can lessen pathohistological damage and apoptosis after AMI. In addition, HQR improves blood fat levels, cardiac function, inflammatory factor, the balance of oxidation and antioxidation, as well as lessen infarction in rats with obesity after AMI. Meanwhile, HQR can diminish myocardial cell death by improving mitochondrial function via PI3K/Akt/Bad pathway activation. In vitro, HQR inhibited H9c2 cells apoptosis, improved mitochondrial function and activated the PI3K/Akt/Bad pathway, but effects can be peripeteiad by LY294002. Myocardial mitochondrial dysfunction occurs following AMI and can lead to myocardial apoptosis, which can be aggravated by obesity. HQR can relieve myocardial apoptosis by improving mitochondrial function via the PI3K/Akt/Bad pathway in rats with obesity.
Assuntos
Infarto do Miocárdio , Fosfatidilinositol 3-Quinases , Animais , Apoptose , Masculino , Mitocôndrias/metabolismo , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Obesidade/complicações , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Qizhiweitong is a famous traditional Chinese prescription medicine. It has been used to treat various stomach disorders, such as functional dyspepsia, chronic gastritis and intestinal stress syndrome, for a long time and gives favorable therapeutic effects in clinical settings. However, its chemical composition and possible bioactive components are not completely known. In the present study, we used ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS) and qualitatively analyzed the chemical composition of Qizhiweitong tablet extract and the absorbed prototype constituents along with corresponding metabolites in rat plasma following oral administration of Qizhiweitong tablet on the basis of our self-developed component database that was established accurately and rapidly. We detected a total of 119 compounds and 61 xenobiotics in the Qizhiweitong tablet, which included 32 prototypes and 28 metabolites. The results of the present study laid a solid foundation for quality marker screening and an integrative pharmacology-based study on the Qizhiweitong tablet.
Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Ratos , Ratos Sprague-Dawley , Comprimidos , Espectrometria de Massas em Tandem/métodosRESUMO
Patrinia villosa (Thunb.) Juss. (PVJ) is described as pungent, bitter and slightly cold in Chinese medicine, and is associated with the large intestine, stomach and liver meridians. The preliminary experiments of our research team proved that PVJ total flavonoids have excellent inhibitory effects on liver cancer cells. The present experiment uses the UPLC-Q-TOF-MS technology and serum pharmacochemistry methods to analyze the chemical components in vitro and in vivo of PVJ antiliver tumors. A total of 14 chemical components were identified in the total flavonoids extract of PVJ, and it is mainly composed of flavonoids, flavonones, flavonols and phenolic acids. At the same time, seven prototypical components and seven metabolic components were detected in the drug-containing plasma. Hydrocaffeate and scutellarein are the phase I metabolites of caffeic acid and scutellarin, respectively. Sulfated apigenin, sulfated luteolin, sulfated kaempferol and methylated kaempferol are the II phase metabolites of apigenin, luteolin, kaempferol, respectively. The experiment provides a reference for the research and development of antitumor drug candidates, and provides a basis for revealing the bioactive components of PVJ and the antitumor mechanism.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Flavonoides/sangue , Patrinia/química , Extratos Vegetais/sangue , Animais , Flavonoides/química , Masculino , Espectrometria de Massas , Extratos Vegetais/química , Ratos , Ratos Sprague-DawleyRESUMO
This study aims to investigate the anticancer effect of Oroxin B (OB) both in vitro and in vivo, and the molecular mechanism involved in microRNA-221 and the PI3K/Akt/PTEN pathway through modulation of apoptosis in Hepatocellular carcinoma (HCC). DEN-induced rats and HepG2 cells based on the microfluidic chip were employed, while the mRNA and protein expression of microRNA-221, PI3K, p-Akt and PTEN were evaluated by RT-PCR and Western blot analysis. Based on Microfluidic Chip and DEN-induced rat model, OB effectively exerts anti-liver cancer effect both in vitro and in vivo, and the expression of miR-221 in OB treated groups was significantly lower than that in the control group (** p < 0.01). The RT-PCR and Western blot results suggested the PI3K mRNA and protein in OB treated groups were both lower than those in control group and indicated the overexpression of PTEN. Therefore, OB effectively exerts anticancer effects by positively regulating the PTEN gene and then inactivating the PI3K/Akt signaling pathway through down-regulating the expression of the microRNA-221, thereby inducing apoptosis of liver cancer cells. This study offers a theoretical evidence for further development and clinical guidance of OB as an anti-tumor agent.
Assuntos
Apoptose/efeitos dos fármacos , Dissacarídeos/farmacologia , Flavonas/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , MicroRNAs/genética , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Biomarcadores , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Histocitoquímica , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , RatosRESUMO
This study was designed to elucidate the chemical composition and anti-cancer effects of Schizonepeta tenuifolia's ethanol extracts. Microfluidic technology was used in the study of Schizonepeta tenuifolia from 9 different geographic regions. The ethanol extracts were examined with HPLC to establish their Fingerprints in order to analyze the relationship between the spectrum and efficacy index through Grey Correlation software, and a rapid HPLC-Q-TOF/MS method was established. The result shows that chromatographic peaks of the 19, 6, 11, 16, 18th are the representative diosmetin, luteoloside, hesperidin, luteolin, and apigenin. The 10, 12, 20th peaks may be naringenin-7-O-glucuronide or quercitrin, rosmarinate or acetylcorynoline, and 5,7-dihydroxy-6,4-dimethoxy flavone. The major chemical composition of Schizonepeta tenuifolia was found to have the anti-lung-tumor effects. A new method was established for the quality control of traditional Chinese medicine.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose , Medicamentos de Ervas Chinesas/farmacologia , Lamiaceae/química , Extratos Vegetais/farmacologia , Apigenina , Cromatografia Líquida de Alta Pressão , Flavonas , Flavonoides , Glucosídeos , Hesperidina , Luteolina , Espectrometria de Massas , MicrofluídicaRESUMO
In order to further clarify the rational use of different medicinal parts of Schizonepeta, microfluidic technology was used in this study to investigate the differences in drug efficacy against lung cancer in vitro. The ethanol extracts were examined with HPLC to establish their fingerprints in order to analyze the relationship between the spectrum and efficacy index through Grey Correlation software, and a rapid HPLC-Q-TOF/MS method was established. The result in vitro shows that the effect and components of different medicinal parts had a certain differences, and apoptosis and necrosis rate from big to small in turn is leaf, flower, root, stem. The chromatographic peaks of the 26, 12, 2, 6 and 15th are the luteolin, icynaroside, rosmarinic, caffeic acid, and hesperidin, while the 20 and 10th may be dan phenolic acid L and benzoic acid. On the one hand, preliminary study reflects that the root of Schizonepeta tenuifolia may be developed into the medicinal parts in future. On the other hand, the major chemical composition of S. tenuifolia was found to have the anti-lung-tumor effects. This new method was established for the quality control and the rational use of different parts of traditional Chinese medicine.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Lamiaceae/química , Neoplasias Pulmonares/tratamento farmacológico , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Humanos , Espectrometria de Massas , Medicina Tradicional Chinesa , MicrofluídicaRESUMO
Two new C21 steroidal glycosides were isolated from Cynanchum otophyllum Schneid. Their structures were elucidated as qinyangshengenin-3-O-ß-d-digitoxopyranoside (1) and rostratamine-3-O-ß-d-cymaropyranosyl-(1 â 4)-ß-d-digitoxopyranoside (2) on the basis of chemical and spectroscopic methods, including 1D and 2D NMR experiments.
Assuntos
Cynanchum/química , Glicosídeos/isolamento & purificação , Esteroides/isolamento & purificação , Glicosídeos/química , Ressonância Magnética Nuclear Biomolecular , Raízes de Plantas/química , Pregnanos , Esteroides/químicaRESUMO
OBJECTIVE: To optimize conditions for extracting total flavonoids from Schizonepeta tenuifolia by the method of analytical hierarchy process with the correlation method of dose-effect. METHODS: Take the amount and concentration of ethanol,the extraction time and times as examine factors, with the inhibition rate of Caco-2 human cloning colonic cancer cell as index to optimize the optimum conditions of total flavonoids from Schizonepeta tenuifolia by orthogonal experiment design, and analyze the Pearson correlation coefficient between the total flavonoids content, hesperidin content, extraction rate and pharmacodynamics indexes through SPSS 19.0 software to determine the dose-effect comparative indicators, and then analytic hierarchy process is adopted to define the weight coefficients range of the content of total flavonoids and hesperidin. RESULTS: The best extraction process conditions were as follows:15 times the amount of 75% ethanol, water circumfluence extracting for 3 times,each time for 2 hours; The weight coefficient ranges of the content of total flavonoids and hesperidin were 0.7500-0.9000 and 0.1000-0.2500 respectively. CONCLUSION: Using the comprehensive scores of the content of total flavonoids and hesperidin, which is calculated by weight coefficient ranges that based on the analytical hierarchy process,to replace the inhibition rate as the indicator to optimize the optimum extraction process is scientific and reasonable. This optimization process is simple and practical,which provides a new method for selecting the best extraction indicators to get effective ingredients from traditional Chinese medicine.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/isolamento & purificação , Lamiaceae/química , Células CACO-2 , Relação Dose-Resposta a Droga , Etanol , Flavonoides/química , Hesperidina/química , Humanos , Tecnologia Farmacêutica , ÁguaRESUMO
Diabetic nephropathy is one of the most significant microvascular complications associated with diabetes. Until now, there is no effective treatment and the gene mechanism of diabetic nephropathy is still unclear. Tangshen formula is a traditional Chinese medicine, and has been shown to have good clinical efficacy in diabetic nephropathy treatment. The objective of this study was to investigate the changes of gene expression profiling and explore the molecular mechanism using a db/db mice model treated by Tangshen formula. After administration for 12 weeks, a microarray was applied to detect the gene expression of db/db mice kidney tissues. Quantitative real-time PCR was used to confirm the differential gene expression and carry out a JAK/STAT/SOCS signaling pathway study. Treatment with Tangshen formula reduced the levels of serum glucose and urinary albumin in db/db mice, and the effects of Tangshen formula on db/db mice were significantly different from the positive control (Losartan potassium tablets) on microarray data. It also showed that the JAK/STAT/SOCS signaling pathway played an important role in the treatment process. The expressions of JAK1, JAK2, and STAT3 were upregulated, and STAT4 was downregulated in Tangshen formula-treated db/db mice. SOCS1, 3, and 7 were all activated, while negative feedback regulated other related genes in the JAK/STAT/SOCS pathway. Our study suggested that Tangshen formula has beneficial effects on diabetic nephropathy treatment via regulating the JAK/STAT/SOCS signaling pathway. This study will help to provide evidence-based recommendations for Tangshen formula clinical treatment.
Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Plantas Medicinais/química , Transdução de Sinais/efeitos dos fármacos , Animais , Análise por Conglomerados , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/isolamento & purificação , Perfilação da Expressão Gênica , Janus Quinases/genética , Rim/efeitos dos fármacos , Masculino , Medicina Tradicional Chinesa , Camundongos , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Transcrição STAT/genética , Proteínas Supressoras da Sinalização de Citocina/genéticaRESUMO
Two new C21 steroidal glycosides were isolated from Cynanchum wallichii Wight. Their structures were elucidated as caudatin-3-O-ß-d-glucopyranosyl-(1 â 4)-ß-d-oleandropyranosyl-(1 â 4)-ß-d-cymaropyranosyl-(1 â 4)-ß-d-digitoxopyranoside (1) and caudatin-3-O-ß-d-glucopyranosyl-(1 â 4)-ß-d-cymaropyranosyl-(1 â 4)-ß-d-oleandropyranosyl-(1 â 4)-ß-d-cymaropyranosyl-(1 â 4)-ß-d-digitoxopyranoside (2) by spectroscopic methods including 1D and 2D NMR experiments.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Cynanchum/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Glicosídeos/isolamento & purificação , Esteroides/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Glicosídeos/química , Glicosídeos/farmacologia , Células HL-60 , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Raízes de Plantas/química , Estereoisomerismo , Esteroides/química , Esteroides/farmacologiaRESUMO
OBJECTIVE: To establish the spectrum-effect relationship network model of Qizhiweitong granules promoting gastrointestinal motility for providing scientific basis for its quality control and efficacy evaluation. METHODS: The Latin hypercube sampling was used to establish full-time multi-wavelength fusion fingerprints of different compatibility groups of Qizhiweitong granules. At the same time, the appreciation rate, the contents of cGMP and NO in small intestine smooth muscle cells after administrated drugs were determined. Then the spectrum-effect relationship of different compatibility groups were correlated, and the network model was established with gray correlation method and BP neural network. RESULTS: 20 compounds with correlation index more than 0.9 were found from 36 constituents in Qizhiweitong granules. The spectrum-effect relationship network model of Qizhiweitong granules promoting gastrointestinal motility was successfully established. And through this model to forecast the result of the test, the absolute value of the relative error was less than 6.83%. CONCLUSION: In this study, a spectrum-effect relationship network model of Qizhiweitong granules promoting gastrointestinal motility is established successfully, which provides a new method for its reasonable quality control and efficacy evaluation, lays the experiment basis for component-effect study, and provides reference for other TCM's study.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Motilidade Gastrointestinal/efeitos dos fármacos , Redes Neurais de Computação , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Intestino Delgado/citologia , Intestino Delgado/efeitos dos fármacos , Modelos Teóricos , Plantas Medicinais/química , Controle de Qualidade , Ratos , Ratos Sprague-Dawley , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: To establish the HPLC fingerprint of flavonoids of Phyllanthi Fructus from different habitats. METHODS: HPLC method was adopted. The flavonoids composition of Phyllanthi Fructus from 10 different habitats was determined on an Agilent C, chromatographic column with 0. 5% formic acid water (A)-acetonitrile (B) as the mobile phase in gradient elution under the wavelength of 254 nm. The HPLC fingerprints of flavonoids composition of Phyllanthi Fructus were established to evaluate the qualitiy of them. RESULTS: The HPLC fingerprints of flavonoids composition of Phyllanthi Fructus from 10 different habitats were established. 18 common peaks were found and the similarities of them were more than 0. 90 except the ones from Guangxi and Guangdong. CONCLUSION: The method is simple, accurate and repeatable. It can be used for research and quality control of the effective components in Phyllanthi Fructus.
Assuntos
Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Flavonoides/análise , Phyllanthus/química , China , Medicamentos de Ervas Chinesas/normas , Ecossistema , Frutas/química , Controle de QualidadeRESUMO
Portulaca oleracea L. are annual herb, which has various pharmacological effects including hepatoprotective property. However, the effect of Portulaca oleracea L. (POL-1) in mice with carbon tetrachloride (CCl4)-induced liver fibrosis and its mechanism of action have not been clarified. POL-1 ameliorated the CCl4-induced liver fibrosis in mice, as shown by decreased collagen deposition and the decreased expression of liver fibrosis marker collagen I and α-smooth muscle actin (α-SMA) mRNA. In addition, treatment with POL-1 suppressed the proliferation of activated human hepatic stellate cell line (LX-2). POL-1 inhibited the oxidative stress and inflammation in fibrotic livers of mice. Mechanistically, POL-1 inhibited the CCl4-induced expression of toll-like receptor-4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor kappa-B (NF-κBp65) p65, Bcl2-associated X (Bax), transforming growth factor-ß1 (TGF-ß1) and drosophila mothers against decapentaplegic 2 (Smad2) proteins, upregulated B-cell lymphoma -2 (Bcl-2) proteins in livers of mice. These findings suggested that POL-1 attenuated liver fibrosis.
RESUMO
This study is the first to examine the effect of leaves of Sambucus williamsii Hance essential oil on acute liver injury. According to gas chromatography-mass spectrometry analysis, the major constituents of S. williamsii essential oil (SEO)were (S)-falcarinol (62.66%), 17-pentatriacontene (7.78%) and tetrapentacontane (8.64%). Mice were pre-treated with SEO for 6 days followed by inducing liver injury with CCl4. The results indicated that SEO protected the liver against CCl4-induced injuries. Elevated levels of alanine-aminotransferase (ALT), aspartate amino-transferase (AST), alkaline phosphatase (ALP) in serum were significantly reduced on SEO pre-treatment. SEO pre-treatment significantly inhibited the oxidative stress and inflammation. Furthermore, toll-like receptor-4 (TLR4)/nuclear factor kappa-B (NF-κB) signalling pathways were significantly modulated by SEO in the liver tissue. The findings demonstrate that the essential oil of S. williamsii has enhancing the resistance to CCl4-induced liver injury.
RESUMO
Diethylnitrosamine (DEN) was applied to create the primary liver cancer (PLC) animal model. In the study, the normal group, model group, cyclophosphamide (CTX) group, Cortex Juglandis Mandshuricae (CJM) extract group, myricetin group and myricitrin group were divided. LC-MS/MS technology was applied to determine the metabolites of liver tissue samples from different locations (nodular and non-nodular parts of liver tissue) in each group of rats. Through metabolomics research, the connection and difference of anti-PLC induced by the CJM extract, myricetin and myricitrin was analyzed. The surface of the liver tissues of rats in the model group was rough, dimly colored, inelastic, on which there were scattered gray white cancer nodules and blood stasis points. The number of cancer nodules was significantly reduced, and the degree of cell malignancy was low, but there were some inflammatory cell infiltrations, necrosis area and karyokinesis in the CJM extract group, myricetin group, myricitrin group and CTX group. The result of metabolic research indicated that 45 potential biomarkers of the PLC were found, as gamma-aminoisobutyrate, taurochenodeoxycholate, xanthurenic acid, etc. There were 22 differential metabolites in the CTX group, 16 differential metabolites in the CJM extract group, 14 differential metabolites in the myricetin group, 14 differential metabolites in the myricitrin group.
Assuntos
Flavonoides , Metabolômica , Extratos Vegetais , Animais , Masculino , Ratos , Dietilnitrosamina/toxicidade , Flavonoides/análise , Flavonoides/farmacologia , Espectrometria de Massa com Cromatografia Líquida , Fígado/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Metabolômica/métodos , Extratos Vegetais/farmacologia , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem/métodosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Colorectal cancer (CRC) belongs to the category of intestinal wind, anal ulcer, abdominal mass and other diseases in traditional Chinese medicine (TCM). Floris Sophorae Powder (F.S), is a classical prescription is recorded in Puji Benshi Fang for the treatment of intestinal carbuncle. It has been incorporated into the prescriptions for the treatment of intestinal diseases and achieved remarkable results in modern medicine. However, the mechanism of F.S in the treatment of colorectal cancer remains unclear and requires further study. AIM OF THE STUDY: To investigate F.S in treating CRC and clarify the underlying mechanism. MATERIALS AND METHODS: This study was based on Dextran Sulfate Sodium Salt (DSS) combined with Azoxymethane (AOM) induced CRC mouse model to clarify the pharmacological effects of F.S. The serum metabolomics was used to study the mechanism of action, and the chemical composition of F.S was found by UPLC-Q-TOF-MS. The rationality of serm metabolomics results was verified through the clinical target database of network pharmacology, and the upstream and downstream targets of related pathways were found. The mechanism pathway was verified by Western blot to clarify its mechanism of action. RESULTS: In vivo pharmacological experiments showed that F.S inhibited tumor growth and improved hematochezia. The vital signs of mice in the high-dose F.S group approached to those in the control group. A total of 43 differential metabolites were found to be significantly changed by serum metabolomics. F.S could modulate and recover most of the differential metabolites, which proved to be closely related to the KRAS/MEK-ERK signaling pathway. A total of 46 compounds in F.S were identified, and the rationality of serm metabolic pathway was verified by network pharmacology. Western blot results also verified that the expression of KRAS, E2F1, p-MEK and p-ERK were significantly decreased after F.S treatment. CONCLUSION: Classical prescription Floris Sophorae Powder treat colorectal cancer by regulating KRAS/MEK-ERK signaling pathway.
Assuntos
Neoplasias Colorretais , Medicamentos de Ervas Chinesas , Animais , Camundongos , Pós/uso terapêutico , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Transdução de Sinais , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Neoplasias Colorretais/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêuticoRESUMO
OBJECTIVE: To establish the chromatography-efficacy relation method for analyzing the anti-inflammatory activity of Qizhi Weitong particles, in order to lay a foundation for quality control and pharmacodynamic evaluation of traditional Chinese medicine compounds. METHOD: On the basis of a full-time multi-wavelength fusion fingerprint of Qizhi Weitong particles, the latin hypercube sampling was used to divide six herbs in Qizhi Weitong particles into groups of different proportions to determine their inhibition ratios of TNF-alpha, IL-6 and NO released by LPS-induced RAW264. 7 cells. Pharmaeodynamic data and chemical information of HPLC fingerprints of each group were analyzed with the gray correlation method to get the anti-inflammatory effect of each chromatographic peak, and then fitted with BP neural network to establish the chromatography-efficacy relation. RESULT: There were 25 peaks closely related to the anti-inflammatory activity. With the 25 peaks as input items, the 3-BP network was adopted to establish the neural network model for anti-inflammatory effect of Qizhi Weitong particles. CONCLUSION: With an error of less than 7%, the model could better fit with the complicated non-linear relation of the compound, and applied in studying the chromatography-efficacy relation. In this study on the chromatography-efficacy relation, a new method is established to evaluate the anti-inflammatory activity of Qizhi Weitong particles. It is of practical significance as an effective approach for controlling quality and exploring the material basis for efficacy of traditional Chinese medicine compounds.
Assuntos
Anti-Inflamatórios/química , Medicamentos de Ervas Chinesas/química , Redes Neurais de Computação , Gastropatias/tratamento farmacológico , Animais , Anti-Inflamatórios/administração & dosagem , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Humanos , Interleucina-6/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Controle de Qualidade , Ratos , Ratos Sprague-Dawley , Gastropatias/imunologia , Fator de Necrose Tumoral alfa/imunologiaRESUMO
OBJECTIVE: To optimize the extraction technology of total flavonoids with antineoplastic activities in Juglans mandshurica, and explore the correlation between total flavonoids and pharmacodynamics indicators. METHODS: The quantity of antineoplastic components, ratio of extraction and cell inhibition rate were taken as the comprehensive indexes to optimize the main factors that influence the extraction of effective components by orthogonal experiment design. SPSS 17.0 software was used to analyze the Pearson correlation between effective components and pharmacodynamics indexes. RESULTS: The best extracting condition of total flavonoids were as follows: the ratio of 60% ethanol to Juglans mandshurica was 20: 1, extracting for 3 times, each time for 2 hour at 70 degrees C. Flavonoids extraction yield and cell inhibition rate was positively related in the straight line. CONCLUSION: This study provides a new insight into the optimization of extraction technology for traditional Chinese medicine, and lays a safe and reliable experimental basis for the clinical application of Juglans mandshurica.
Assuntos
Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Juglans/química , Casca de Planta/química , Tecnologia Farmacêutica/métodos , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Etanol/química , Humanos , Neoplasias Hepáticas/patologia , Espectrofotometria Ultravioleta , TemperaturaRESUMO
OBJECTIVE: To investigate the inhibitory effects of flavonoids of Polygoni Orientails Fructus on cell cycle and apoptosis of human hepatoma cell line SMMC-7721. METHODS: MTT method was used to study the inhibitory rate and time-dose relationship of flavonoids on SMMC-7721. Flow cytometry PI staining and Annexin V-EGFP/PI double staining were used to measure the DNA concentration and apoptosis rate in SMMC-7721. RESULTS: Flavonoids of Polygoni Orientails Fructus had obvious inhibitory effect and with good linear relationship between time and dose. Flavonoids of Polygoni Orientails Fructus could regulate the G1/S transition in hepatoma cell, which could make the cell in S phase arrest, result in the accumulation of cells in S phase, blocked DNA synthesis and replication of cells, blocked tumor cells into the G2/M phase, so as to restrain the proliferation of tumor cells and induce the apoptosis of SMMC-7721 cells. And this inductive effect showed obvious time-dose-effect relationship. CONCLUSION: The flavonoids of Polygoni Orientails Fructus could inhibit the hepatoma cell line SMMC-7721 in vitro by inhibiting cell proliferation and inducing apoptosis of the cell in a time-dose dependence maner.