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1.
J Ethnopharmacol ; 264: 113052, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32535239

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bge. as a traditional Asian medicinal plant, roots and rhizomes (Danshen) are used to treat chronic hepatitis and coronary heart disease. In recent years, the medicinal value of S. miltiorrhiza stems and leaves total phenolic acids extract (JF) similar to roots and rhizomes has received increasing attention. S. miltiorrhiza roots and rhizome tanshinone extract (DT) has a good anti-inflammatory effect. AIM OF THE STUDY: To explore the therapeutic effect and possible molecular mechanisms of JF and DT alone or in combination on dextran sulfate sodium (DSS)-induced colitis mice. MATERIALS AND METHODS: Colitis was induced by received 2% DSS in drinking water for 7 consecutive days. Then mice were administered orally for 7 days. Disease activity index (DAI) scores and body weight were recorded daily. After the end of the experiment, colon was removed, colon length was measured and histopathological analysis was performed. Inflammatory factors expression was determined by ELISA, its mRNA expression was detected by real-time quantitative PCR, and the expression of related proteins on TLR4/PI3K/AKT/mTOR signal was analyzed by Western blot. RESULTS: Treatment with JF and DT alone or in combination reduced DAI scores, increase body weight, improved colon shortening, and decreased colon histology scores. In addition, the expression level of inflammatory factors was inhibited. The combination of JF and DT had a better inhibitory effect on inflammatory factors compared to JF alone. We also found that DT alone and JF combined with DT inhibited TLR4/PI3K/AKT/mTOR signaling-related proteins expression levels (including TLR4, p-PI3K p110α/PI3K p110α, p-AKT (ser473)/AKT, mTOR, p-mTOR, NF-κB p65), showing an effective anti-inflammatory effect. CONCLUSIONS: We demonstrated for the first time that, JF and DT alone or in combination effectively ameliorated DSS-induced ulcerative colitis in mice, possibly by inhibiting the TLR4/PI3K/AKT/mTOR signaling pathway.

2.
Molecules ; 24(21)2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31683684

RESUMO

Frankincense and myrrha (FM), commonly used as a classical herbal pair, have a wide range of clinical applications and definite anti-inflammatory activity. However, anti-neuroinflammation effects and mechanisms are not clear. In this study, we adopted a lipopolysaccharide (LPS)-induced microglial (BV2) cell model and a network pharmacology method to reveal the anti-neuroinflammatory effects and mechanisms of boswellic acid (BA) and myrrha sesquiterpenes (MS) with different proportions of compatibility. The data showed that the different ratios of BA and MS had different degrees of inhibition of interleukin-1ß (IL-1ß), IL-6, and inducible nitric oxide synthase (iNOS) mRNA expression, down-regulated the phosphor-nuclear factor kappa B/nuclear factor kappa B (p-NF-Ò¡B)/(NF-Ò¡B), phosphorylated protein kinase b/protein kinase b (p-AKT/AKT), and Toll-like receptor 4 (TLR4) protein expression levels, and increased phospho-PI3 kinase (p-PI3K) protein expression levels. When the ratios of BA and MS were 10:1, 5:1, and 20:1, better effective efficacy was exhibited. According to the correlation analysis between the effect index and bioactive substances, it was suggested that 2-methoxy-5-acetoxy -fruranogermacr-1(10)-en-6-one (Compound 1), 3α-acetyloxylanosta-8,24-dien-21-oic acid (Compound 2), 11-keto-boswellic acid (Compound 3), and 3-acetyl-11-keto-ß -boswellic acid (Compound 4) made important contributions to the treatment of neuroinflammation. Furthermore, based on the network pharmacological analysis, it was found that these four active compounds acted on 31 targets related to neuroinflammation and were involved in 32 signaling pathways which mainly related to the immune system, cardiovascular system, and nervous system, suggesting that BA and MS could be used to treat neuroinflammation.


Assuntos
Commiphora/química , Inflamação/tratamento farmacológico , Microglia/patologia , Fármacos Neuroprotetores/uso terapêutico , Sesquiterpenos/uso terapêutico , Triterpenos/uso terapêutico , Animais , Linhagem Celular , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Ontologia Genética , Inflamação/patologia , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolissacarídeos , Camundongos , Microglia/efeitos dos fármacos , NF-kappa B/metabolismo , Fármacos Neuroprotetores/farmacologia , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sesquiterpenos/farmacologia , Receptor 4 Toll-Like/metabolismo , Triterpenos/farmacologia
3.
J Laparoendosc Adv Surg Tech A ; 29(12): 1544-1548, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31613691

RESUMO

Objective: This study was to introduce the modified mini-laparoscopic adrenalectomy and investigate the advantage of operative time, cosmetic effect, and pain reduction by comparing the modified mini-laparoscopic adrenalectomy and laparoendoscopic single-site surgery (LESS). Methods and Patients: Between May 2015 and Jun 2018, 76 consecutive patients with adrenal tumor underwent laparoscopic adrenalectomy. Of which, 36 cases were in the mini-laparoscopic surgery group (the M group) and 40 cases in the LESS group. Medical records of the consecutive patients were analyzed. The operative time, blood loss, the Visual Analog Scale (VAS) scores and the Scar Cosmesis Assessment and Rating (SCAR) Scale scores were recorded. Results: The mean operative time in the M group was significantly less than that of in the LESS group (54.75 ± 9.37 min vs. 106.48 ± 19.71 min, P < .01). Mean estimated blood loss did not differ between the 2 groups (12.22 ± 5.29 mL vs. 10.80 ± 6.66 mL, P > .05). The mean VAS scores in the M group were significantly lower than those of the LESS group on postoperative days (POD) 1 and 3. The SCAR scale scores at POD 60 were similar in the M group and the LESS group (0.86 ± 0.64 vs. 0.95 ± 0.71, P > .05). Conclusions: Modified mini-laparoscopic adrenalectomy is safe and convenient. It offered less operative time, significant cosmetic benefit, and reduced incisional pain.


Assuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/métodos , Endoscopia/métodos , Laparoscopia/métodos , Dor Pós-Operatória/prevenção & controle , Adulto , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Cicatriz/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia
4.
Phytother Res ; 33(8): 2044-2055, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31209937

RESUMO

Mulberry leaf was reported that it has antidiabetic activity, although the mechanisms underlying the function have not been fully elucidated. In the present study, the results of network pharmacology suggested that mulberry leaves could regulate key biological process in development of diabetes, and the process implicates multiple signaling pathways, such as JAK-STAT, MAPK, VEGF, PPAR, and Wnt. Then, the research in vitro indicated that mulberry leaves remarkably ameliorated high glucose-induced epithelial to mesenchymal transition, which was characterized with significant reduction of intracellular reactive oxygen species (ROS) levels as well as downregulation of NADPH oxidase subunits NOX1, NOX2, and NOX4, and it was found to be connected with the ERK1/2 signaling pathway in human tubular epithelial cells (HK-2). Moreover, the results of bioinformatics and the dual luciferase report showed that ZEB1 might be a target gene of miR-302a; decreased miR-302a and increased ZEB1 expressions could significantly promote epithelial to mesenchymal transition. However, mulberry leaves could reverse these modulations. Our results demonstrated that network pharmacology could provide a guidance role for traditional Chinese medicine research, and mulberry leaves could be of benefit in preventing high glucose-induced EMT in HK-2 cells, which proved that it was related to the upregulation of miR-302a by targeting ZEB1 and the inhibition of NADPH oxidase/ROS/ERK1/2 pathway.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Células Epiteliais/metabolismo , Nefropatias/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Morus/química , NADPH Oxidases/metabolismo , Folhas de Planta/química , Espécies Reativas de Oxigênio/metabolismo , Transição Epitelial-Mesenquimal , Humanos , Nefropatias/patologia
5.
Urol J ; 16(6): 547-551, 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31134608

RESUMO

PURPOSE: This study was to introduce the modified mini-laparoscopic surgery for renal cyst and investigate itsadvantages on operative time, cosmetic effect and pain reduction by comparison with laparo-endoscopic single sitesurgery (LESS) and conventional laparoscopic surgery. METHODS AND PATIENTS: Between May 2015 and October 2018, 140 consecutive patients with benign renal cystunderwent laparoscopic decortication of renal cyst. Of which, 48 cases were in mini-laparoscopic surgery group(M group), 56 cases in LESS group and 36 cases in conventional laparoscopic surgery group (C group). The operativetime, blood loss, visual analog scale (VAS) and Scar Cosmesis Assessment and Rating (SCAR) Scale wasrecorded. RESULTS: The mean operative time in M group (26.08±7.70 min) and C group (28.56 ± 7.99 min). was significantlyless than that in LESS group (47.32 ±10.53 min) (P < 0.01). Mean blood loss did not differ between the 3 groups(P > 0.05). Mean VAS pain scores in M group were significantly lower than that of LESS group and C group onpostoperative day (POD) 1 and 3 (P < 0.01). The SCAR scale of POD 30 in C group (6.25 ± 1.0) was significantlyhigher than that in M group (0.77 ± 0.59) and LESS group (0.98 ± 0.70). The postoperative course was uneventfulwith no morbidity within 1to 6 months of follow-up. CONCLUSION: Modified mini-laparoscopic decortication of renal cyst have more comprehensive advantages comparingwith LESS and conventional laparoscopic surgery. It is convenient and offered significant cosmetic benefitand reduced incisional pain.

7.
Target Oncol ; 14(2): 187-195, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30887420

RESUMO

BACKGROUND: Serum protein fraction (SPF) is a common parameter reflecting the nutritional and inflammatory status of the human body. However, its role in patients with cancer, particularly those treated with targeted agents, is unknown. OBJECTIVE: We conducted this study to explore the prognostic value of SPF in patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors and its association with clinical characteristics. METHODS: Patients with mRCC (n = 213) who initiated first-line sunitinib or sorafenib systemic therapy for metastatic disease between March 2007 and June 2017 at Zhongshan Hospital, Fudan University, were retrospectively included in our analysis. Clinical and pathological data were collected. SPF was measured by capillary electrophoresis. Prognostic factors of overall survival (OS) and progression-free survival (PFS) were analyzed using the Cox proportional hazards model. Correlation was estimated with Spearman's correlation coefficient. RESULTS: Among all SPF components, high α1-globulin was an independent prognostic factor for OS and PFS (dichotomized by median, hazard ratio [HR] 2.356; 95% confidence interval [CI] 1.399-3.966, p = 0.001; and HR 1.994; 95% CI 1.360-2.923, p < 0.001, respectively). In our cohort, α1-globulin showed better predictive value for OS than the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model (C-index 0.682 vs. 0.597; p = 0.005). Moreover, serum α1-globulin was positively correlated with International Society of Urological Pathology (ISUP) grade (r = 0.237; p < 0.001), tumor size (r = 0.242; p < 0.001), initial tumor/node/metastasis (TNM) stage (r = 0.185; p = 0.007), and IMDC risk group (r = 0.485; p < 0.001). CONCLUSIONS: High serum α1-globulin correlates with high tumor load. Serum α1-globulin is an independent prognostic factor of OS and PFS in mRCC and demonstrates better predictive value for OS than does the IMDC model.


Assuntos
alfa-Globulinas/análise , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Carcinoma de Células Renais/secundário , Neoplasias Renais/patologia , Idoso , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/tratamento farmacológico , Feminino , Seguimentos , Humanos , Neoplasias Renais/sangue , Neoplasias Renais/tratamento farmacológico , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Sorafenibe/administração & dosagem , Sunitinibe/administração & dosagem , Taxa de Sobrevida
8.
World J Gastroenterol ; 25(7): 848-858, 2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30809084

RESUMO

BACKGROUND: Embolic superior mesenteric artery (SMA) occlusion is associated with high mortality rates. Delayed treatment often leads to serious consequences, including intestinal necrosis, resection, and even patient death. Endovascular repair is being introduced, which can improve clinical symptoms and prognosis and decrease the incidence of exploratory laparotomy. Many reports have described successful endovascular revascularization of embolic SMA occlusion. However, most of those reports are case reports, and there are few reports on Chinese patients. In this paper, we describe the technical and clinical outcomes of aspiration therapy using a guiding catheter and long sheath technique which facilitates the endovascular repair procedure. AIM: To evaluate the complications, feasibility, effectiveness, and safety of endovascular treatment for the acute embolic occlusion of the SMA. METHODS: This retrospective study reviewed eight patients (six males and two females) from August 2013 to October 2018 at Xuanwu Hospital, Capital Medical University. The patients presented with acute embolic occlusion of the SMA on admission and were initially diagnosed by computed tomography angiography (CTA). The patients who underwent endovascular treatment with a guiding catheter had no obvious evidence of bowel infarct. No intestinal necrosis was identified by gastrointestinal surgeons through peritoneal puncture or CTA. The complications, feasibility, effectiveness, safety, and mortality were assessed. RESULTS: Six (75%) patients were male, and the mean patient age was 70.00 ± 8.43 years (range, 60-84 years). The acute embolic occlusion of the SMA was initially diagnosed by CTA. All patients had undertaken anticoagulation primarily, and percutaneous aspiration using a guiding catheter was then undertaken because the emboli had large amounts of thrombus residue. No death occurred among the patients. Complete patency of the suffering artery trunk was achieved in six patients, and defect filling was accomplished in two patients. The in-hospital mortality was 0%. The overall 12-mo survival rate was 100%. All patients survived, and two of the eight patients had complications (the clot broke off during aspiration). CONCLUSION: Aspiration therapy is feasible, safe, and beneficial for acute embolic SMA occlusion. Aspiration therapy has many benefits for reducing patients' death, resolving thrombi, and improving symptoms.


Assuntos
Anticoagulantes/uso terapêutico , Procedimentos Endovasculares/métodos , Oclusão Vascular Mesentérica/terapia , Complicações Pós-Operatórias/epidemiologia , Tromboembolia/terapia , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Angiografia por Tomografia Computadorizada , Procedimentos Endovasculares/efeitos adversos , Estudos de Viabilidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Artéria Mesentérica Superior/diagnóstico por imagem , Artéria Mesentérica Superior/patologia , Oclusão Vascular Mesentérica/complicações , Oclusão Vascular Mesentérica/diagnóstico por imagem , Oclusão Vascular Mesentérica/mortalidade , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Stents , Sucção/efeitos adversos , Sucção/métodos , Taxa de Sobrevida , Tromboembolia/complicações , Tromboembolia/diagnóstico por imagem , Resultado do Tratamento
9.
Pharmacol Res ; 139: 26-40, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30395946

RESUMO

Diabetic nephropathy (DN) is a complication of diabetes that is caused by uncontrolled high blood sugar. It has been reported that Salvia miltiorrhiza (SM) possesses the ability to prevent kidney damage, although the mechanisms remain unclear. The study was to investigate whether and how SM improved DN injury via regulation of metabolome and the molecular mechanisms. In this study, SD rats were fed a high glucose / high fat diet accompanied by 0.5% glucose water. Three weeks later, the rats were given one intraperitoneal injection of 30 mg/kg STZ each day for three days for DN model. The biochemical indicators and metabolomics of plasma, urine and renal tissue were analyzed. Then the western blotting analysis of renal tissue and glomerular mesangial cells were investigated. The results showed that Salvia miltiorrhiza extracts improved the renal injury and regulation of abnormal glycolipid metabolism. The metabolites in serum, urine and renal tissues have been changed significantly. The involved metabolic pathways mainly include phospholipid, arachidonic acid, and pyrimidine metabolisms. Meanwhile, SM inhibited the relative expression levels of wnt4, ß-catenin and TGF-ß in renal tissue and high-glucose induced glomerular mesangial cells.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Metaboloma/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Salvia miltiorrhiza , Animais , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Ratos Sprague-Dawley , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Proteínas Wnt/metabolismo , beta Catenina/metabolismo
10.
J Cancer ; 9(22): 4099-4107, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30519309

RESUMO

We conducted this study to determine whether immunoscore system (IS) predicts survival in patients with metastatic renal cell carcinoma (mRCC). A total of 218 mRCC patients treated with sunitinib or sorafenib in Zhongshan Hospital, Fudan University were recruited during 2007-2017, retrospectively. CD8, CD4, Treg, PD-1 and PD-L1 expression were evaluated by immunohistochemical staining of paraffin embedded slide. Kaplan-Meier method and COX regression model were used in survival analyses. Multivariate analyses demonstrated that expressions of CD8, Treg, PD-1 and stromal PD-L1 (sPD-L1) expressions were independent predictive factors for OS, thus IS was established containing these four immunological factors. Subsequent analysis revealed that performance of IS provided good differentiation of OS and PFS. Besides, multivariate analysis identified IS as an independent prognostic factor for OS (p<0.001) and PFS (p=0.002). IS, compared with International mRCC Database Consortium (IMDC) risk model, and provided better prediction ability for OS. Results suggested that IS was a powerful prognostic factor for OS and PFS in patients with mRCC treated with tyrosine kinase inhibitors. And IS can be used as essential supplement to IMDC for outcome prediction in mRCC patients.

11.
Front Pharmacol ; 9: 746, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30042683

RESUMO

Studies have indicated that Chrysanthemum polysaccharides (CP) could prominently ameliorate colitis rats, but its possible mechanism remains unclear. In this study, the underlying mechanism of CP was explored by the metabolic profiling analysis and correlated signaling pathways. TNBS/ethanol induced colitis was used to investigate the intervention efficacy following oral administration of CP. The levels of cytokines such as TNF-α, IL-6, IFN-γ and IL-1ß, and the activities of SOD, MPO, and MDA were determined. We also performed western-blot for p65, TLR4, p-JAK2, and STAT3 protein expression in the colon tissue to probe their mechanisms of correlated signaling pathways. What's more, the metabolic changes in plasma and urine from colitis rats were investigated based on UPLC-Q-TOF/MS combined with MetabolynxTM software. The potential biomarkers and metabolic pathways were also tentatively confirmed. The metabolic profiles of plasma and urine were clearly improved in model rats after oral administration of CP. Thirty-two (17 in serum and 15 in urine) potential biomarkers were identified. The endogenous metabolites were mainly involved in linoleic acid, retinol, arachidonic acid, glycerophospholipid and primary bile acid metabolism in plasma, and nicotinate and nicotinamide, ascorbate and aldarate, histidine and ß-alanine metabolism in urine. After polysaccharides intervention, these markers turned back to normal level at some extent. Meanwhile, the elevated expression levels of pp65, TLR4, p-STAT3, and p-JAK2 were significantly decreased after treatment. Results suggested that CP would be a potential prebiotics for alleviation of TNBS-induced colitis. The study paved the way for the further exploration of the pathogenesis, early diagnosis and curative drug development of the colitis.

12.
Zhongguo Zhong Yao Za Zhi ; 43(2): 369-371, 2018 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-29552857

RESUMO

The study was based on the toxic characteristics of the compatibility between "Zaojisuiyuan" and Gancao, with intestinal tract and intestinal bacteria as subject. From the angle of intestinal barrier function, motor function, steady state of intestinal flora and metabolism genes, the toxic and side effects of the compatibility between Qianjinzi and Gancao with similar properties, bases and chemical composition and types were further explored. The results showed that the combined application of Qianjinzi and Gancao enhanced intestinal mucosa damage, and led to abnormal changes in intestinal bacteria structure and metabolic function. It improved the degradation functions of mucus and aromatic amino acids on intestinal bacteria, which may increase the risk of disease and derived from intestinal urotoxin and other toxic substances. This study considered intestinal bacteria as an important target to study the interactions of traditional Chinese medicine. The "drug-intestinal bacteria-metabolism-toxicity" was applied in the experiment. Meanwhile, it provides ideas for exploring incompatible mechanism of traditional Chinese medicines.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Glycyrrhiza uralensis/química , Mucosa Intestinal/efeitos dos fármacos , Animais , Mucosa Intestinal/patologia , Medicina Tradicional Chinesa
13.
Zhongguo Zhong Yao Za Zhi ; 42(21): 4218-4225, 2017 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-29271164

RESUMO

To study the pharmacokinetic effect of Mori Folium flavones and alkaloids in normal and diabetic rats. An UPLC-TQ-MS method was developed for the simultaneous determination of rutin, isoquercitrin, astragalin, kaempferol, quercetin, chlorogenic acid, cryptochlorogenic acid, neochlorogenic acid, DNJ and fagomine in plasma of rats. The diabetic rat model was induced through intravenous injection with alloxan and high-fat diet. Samples of plasma of rats were obtained at different time points, after the rats were administrated with Mori Folium flavones and alkaloids. After the deproteinization with acetonitrile, the concentrations of Mori Foliam constituents in rats at different time points were detected by UPLC-TQ-MS method, and pharmacokinetic parameters were calculated by DAS 2.0 software. The results showed that quercetin and kaempferol reached peak at 0.333 h, indicating that Mori Folium flavonoid constituents were absorbed and distributed quickly. At about 4 h after administration, both of them reached the peak concentrations for the second time, suggesting that they stayed in intestine for a long time. DNJ and fagomine in gastrointestinal tract can be quickly absorbed into blood, and the concentration in plasma reached peak after 0.667 h, suggesting that both of them could be rapidly distributed in the systemic circulation of rats. Cryptochlorogenic acid, neochlorogenic acid, quercetin, kaempferol and rutin were found to have a higher Cmax and AUC0-t in normal rats than those in diabetic rats. The t1/2values of cryptochlorogenic acid and neochlorogenic acid were shorter in diabetic rats, while quercetin, kaempferol and rutin had a longer t1/2value in diabetic rats. Chlorogenic acid, astragalin, isoquercitrin, fagomine had a higher Cmax in diabetic rats, and the t1/2values of astragalin and fagomine were longer, which suggested differences in absorption of active ingredients under normal and diabetic conditions.


Assuntos
Alcaloides/farmacocinética , Diabetes Mellitus Experimental/tratamento farmacológico , Flavonas/farmacocinética , Morus/química , Folhas de Planta/química , Animais , Cromatografia Líquida de Alta Pressão , Compostos Fitoquímicos/farmacocinética , Ratos , Espectrometria de Massas em Tandem
14.
Front Pharmacol ; 8: 833, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29187820

RESUMO

Stability of traditional Chinese medicine injection (TCMI) is an important issue related with its clinical application. TCMI is composed of multi-components, therefore, when evaluating TCMI stability, several marker compounds cannot represent global components or biological activities of TCMI. Till now, when evaluating TCMI stability, method involving the global components or biological activities has not been reported. In this paper, we established a comprehensive strategy composed of three different methods to evaluate the chemical and biological stability of a typical TCMI, Danhong injection (DHI). UHPLC-TQ/MS was used to analyze the stability of marker compounds (SaA, SaB, RA, DSS, PA, CA, and SG) in DHI, UHPLC-QTOF/MS was used to analyze the stability of global components (MW 80-1000 Da) in DHI, and cell based antioxidant capability assay was used to evaluate the bioactivity of DHI. We applied this strategy to assess the compatible stability of DHI and six infusion solutions (GS, NS, GNS, FI, XI, and DGI), which were commonly used in combination with DHI in clinic. GS was the best infusion solution for DHI, and DGI was the worst one based on marker compounds analysis. Based on global components analysis, XI and DGI were the worst infusion solutions for DHI. And based on bioactivity assay, GS was the best infusion solution for DHI, and XI was the worst one. In conclusion, as evaluated by the established comprehensive strategy, GS was the best infusion solution, however, XI and DGI were the worst infusion solutions for DHI. In the compatibility of DHI and XI or DGI, salvianolic acids in DHI would be degraded, resulting in the reduction of original composition and generation of new components, and leading to the changes of biological activities. This is the essence of instability compatibility of DHI and some infusion solutions. Our study provided references for choosing the reasonable infusion solutions for DHI, which could contribute the improvement of safety and efficacy of DHI. Moreover, the established strategy may be applied for the compatible stability evaluation of other TCMIs.

15.
Zhongguo Zhong Yao Za Zhi ; 42(15): 3017-3025, 2017 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-29139273

RESUMO

To evaluate the promoting blood circulation and removing blood stasis effects of Danshen-Honghua(DH) herb pair with different preparations (alcohol, 50% alcohol and water) on blood rheology and coagulation functions in acute blood stasis rats, and optimize the best preparation method of DH based on principal component analysis(PCA), hierarchical cluster heatmap analysis and multi-attribute comprehensive index methods. Ice water bath and subcutaneous injection of adrenaline were both used to establish the acute blood stasis rat model. Then the blood stasis rats were administrated intragastrically with DH (alcohol, 50% alcohol and water) extracts. The whole blood viscosity(WBV), plasma viscosity(PV), erythrocyte sedimentation rate(ESR) and haematocrit(HCT) were tested to observe the effects of DH herb pair with different preparations and doses on hemorheology of blood stasis rats; the activated partial thromboplastin time(APTT), thrombin time(TT), prothrombin time(PT), and plasma fibrinogen(FIB) were tested to observe the effects of DH herb pair with different preparations on blood coagulation function and platelet aggregation of blood stasis rats. Then PCA, hierarchical cluster heatmap analysis and multi-attribute comprehensive index methods were all used to comprehensively evaluate the total promoting blood circulation and removing blood stasis effects of DH herb pair with different preparations. The hemorheological indexes and coagulation parameters of model group had significant differences with normal blank group. As compared with the model group, the DH herb pair with different preparations at low, middle and high doses could improve the blood hemorheology indexes and coagulation parameters in acute blood stasis rats with dose-effect relation. Based on the PCA, hierarchical cluster heatmap analysis and multi-attribute comprehensive index methods, the high dose group of 50% alcohol extract had the best effect of promoting blood circulation and removing blood stasis. Under the same dose but different preparations, 50% alcohol DH could obviously improve the hemorheology and blood coagulation function in acute blood stasis rats. These results suggested that DH herb pair with different preparations could obviously ameliorate the abnormality of hemorheology and blood coagulation function in acute blood stasis rats, and the optimized preparation of DH herb pair on promoting blood effects was 50% alcohol extract, providing scientific basis for more effective application of the DH herb pair in modern clinic medicine.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Hemorreologia , Salvia miltiorrhiza/química , Animais , Carthamus tinctorius/química , Fibrinogênio/análise , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Ratos , Tempo de Trombina
16.
Clin Cancer Res ; 23(21): 6580-6591, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28808038

RESUMO

Purpose: Activation of the PI3K pathway occurs in over 40% of bladder urothelial cancers. The aim of this study is to determine the therapeutic potential, the underlying action, and the resistance mechanisms of drugs targeting the PI3K pathway.Experimental Design: Urothelial cancer cell lines and patient-derived xenografts (PDXs) were analyzed for alterations of the PI3K pathway and for their sensitivity to the small-molecule inhibitor pictilisib alone and in combination with cisplatin and/or gemcitabine. Potential predictive biomarkers for pictilisib were evaluated, and RNA sequencing was performed to explore drug resistance mechanisms.Results: The bladder cancer cell line TCCSUP, which harbors a PIK3CA E545K mutation, was sensitive to pictilisib compared to cell lines with wild-type PIK3CA Pictilisib exhibited stronger antitumor activity in bladder cancer PDX models with PI3KCA H1047R mutation or amplification than the control PDX model. Pictilisib synergized with cisplatin and/or gemcitabine in vitro, significantly delayed tumor growth, and prolonged survival compared with single-drug treatment in the PDX models. The phosphorylation of ribosomal protein S6 correlated with response to pictilisib both in vitro and in vivo, and could potentially serve as a biomarker to predict response to pictilisib. Pictilisib activated the compensatory MEK/ERK pathway that likely contributed to pictilisib resistance, which was reversed by cotreatment with the RAF inhibitor sorafenib. RNA sequencing of tumors resistant to treatment suggested that LSP1 downregulation correlated with drug resistance.Conclusions: These preclinical results provide new insights into the therapeutic potential of targeting the PI3K pathway for the treatment of bladder cancer. Clin Cancer Res; 23(21); 6580-91. ©2017 AACR.


Assuntos
Classe I de Fosfatidilinositol 3-Quinases/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fosfatidilinositol 3-Quinase/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Indazóis/administração & dosagem , Indazóis/efeitos adversos , Camundongos , Mutação , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
17.
J Sep Sci ; 40(17): 3392-3401, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28657142

RESUMO

A sensitive, reliable, and powerful ultra-high performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry method was developed for simultaneous quantification of the 15 main bio-active components including phenolic acids and flavonoids within 13 min for the first time. The proposed method was first reported and validated by good linearity (r2  > 0.9975), limit of detection (1.12-7.01 ng/mL), limit of quantification (3.73-23.37 ng/mL), intra- and inter-day precisions (RSD ≤ 1.92%, RSD ≤ 2.45%), stability (RSD ≤ 5.63%), repeatability (RSD ≤ 4.34%), recovery (96.84-102.12%), and matrix effects (0.92-1.02). The established analytical methodology was successfully applied to comparative analysis of main bio-active components in the herb pair Danshen-Honghua and its single herbs. Compared to the single herb, the content of most flavonoid glycosides was remarkably increased in their herb pair, and main phenolic acids were decreased, conversely. The content changes of the main components in the herb pair supported the synergistic effects on promoting blood circulation and removing blood stasis. The results provide a scientific basis and reference for the quality control of Danshen-Honghua herb pair and the drug interactions based on variation of bio-active components in herb pairs.


Assuntos
Medicamentos de Ervas Chinesas/análise , Salvia miltiorrhiza/química , Carthamus tinctorius/química , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas em Tandem
18.
World J Surg Oncol ; 15(1): 53, 2017 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-28245846

RESUMO

BACKGROUND: The objective of this study is to investigate the optimal therapeutic protocol for BSSRCC. METHODS: A total of 32 BSSRCC patients, including 28 males and 4 females, were enrolled the study from January 2004 to May 2016. The diagnoses were defined by the measurements of CT, ultrasound, and MRI. Patients with hereditary syndrome were excluded. The management of surgical manner, operation staging, and sequence were scheduled in accordance with the tumor's location and size (based on Zhongshan score, ZS score), as well as the performance status of the patients. Among them, 8 cases were conducted with bilateral surgical procedure simultaneously and 24 cases were implemented with staged operations. NSS on the one side with contralateral RN, and NSS on both sides were performed in 17 and 15 patients separately. RESULTS: Thirty cases were conducted 56 operations in total. The average operation time was 260 ± 52 min in simultaneous operations and 162 ± 40 min in staged operations. The length of hospital stay in average was 11.5 ± 1.8 and 7.5 ± 1.4 days, respectively. Twenty-eight cases were followed up by 6-138 months. The level of creatinine was elevated in 5 cases without hemodialysis conducted. CONCLUSIONS: The location and size of the carcinomas, and the performance status of patients should be considered in determination of an appropriate surgical approach. Both renal function preservation and tumor eradication were similarly critical, whereas the latter is of more importance. ZS score may be helpful in the dilemma. Longer follow-up period and more patient enrolment are required.


Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Nefrectomia , Complicações Pós-Operatórias , Adulto , Idoso , Carcinoma de Células Renais/patologia , China , Feminino , Seguimentos , Hospitais Universitários , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida
19.
J Pharm Biomed Anal ; 138: 109-117, 2017 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-28192718

RESUMO

Acetylsalicylic acid (Aspirin, ASA) is a famous drug for cardiovascular diseases in recent years. Effects of ASA dosage on the metabolic profile have not been fully understood. The purpose of our study is to establish a rapid and reliable method to quantify ASA metabolites in biological matrices, especially for glucuronide metabolites whose standards are not commercially available. Then we applied this method to evaluate the effects of ASA dosage on the metabolic and excretion profile of ASA metabolites in rat urine. Salicylic acid (SA), gentisic acid (GA) and salicyluric acid (SUA) were determined directly by UHPLC-MS/MS, while salicyl phenolic glucuronide (SAPG) and salicyluric acid phenolic glucuronide (SUAPG) were quantified indirectly by measuring the released SA and SUA from SAPG and SUAPG after ß-glucuronidase digestion. SUA and SUAPG were the major metabolites of ASA in rat urine 24h after ASA administration, which accounted for 50% (SUA) and 26% (SUAPG). When ASA dosage was increased, the contributions dropped to 32% and 18%, respectively. The excretion of other three metabolites (GA, SA and SAPG) however showed remarkable increases by 16%, 6% and 4%, respectively. In addition, SUA and SUAPG were mainly excreted in the time period of 12-24h, while GA was excreted in the earlier time periods (0-4h and 4-8h). SA was mainly excreted in the time period of 0-4h and 12-24h. And the excretion of SAPG was equally distributed in the four time periods. We went further to show that the excretion of five metabolites in rat urine was delayed when ASA dosage was increased. In conclusion, we have developed a rapid and sensitive method to determine the five ASA metabolites (SA, GA, SUA, SAPG and SUAPG) in rat urine. We showed that ASA dosage could significantly influence the metabolic and excretion profile of ASA metabolites in rat urine.


Assuntos
Aspirina/metabolismo , Aspirina/urina , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Animais , Aspirina/química , Glucuronatos/química , Glucuronatos/urina , Glucuronidase/química , Glucuronídeos/química , Glucuronídeos/urina , Hipuratos/química , Hipuratos/urina , Masculino , Metaboloma/fisiologia , Ratos , Ratos Sprague-Dawley , Salicilatos/química , Salicilatos/urina , Ácido Salicílico/química , Ácido Salicílico/urina
20.
Biomed Chromatogr ; 31(2)2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27451133

RESUMO

Flos Abelmoschus manihot is a traditional herbal medicine widely used in clinical practice to tackle chronic kidney disease (CKD) for thousands of years. Nowadays, many studies indicate that gut bacteria are closely related to the progression of CKD and CKD-related complications. In this study, a UPLC-Q-TOF/MS method coupled with the MetaboLynx™ software was established and successfully applied to investigate the metabolites and metabolic profile of Flos A. manihot extract by intestinal bacteria from normal and CKD rats. Eight parent components and eight metabolites were characterized by their protonated ions. Among these compounds, 15 were detected in the two group samples while M16 was only determined in the CKD model samples. Compared with the quercetin-type glycosides, fewer myricetin-type and gossypetin-type metabolites were obtained in the two group samples. These metabolites suggested that deglycosylation and methylation are the major metabolic pathways of Flos A. manihot extract. Few differences of metabolite classes were observed in the two group samples. However, the concentrations of aglycones such as quercetin, myricetin and gossypetin in the normal samples were notably higher than those in the CKD model samples. The results are important in unravelling the pharmacological effects of A. manihot and clarifying its mechanism of action in vivo.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/metabolismo , Intestinos/microbiologia , Insuficiência Renal Crônica/microbiologia , Abelmoschus , Animais , Cromatografia Líquida de Alta Pressão/métodos , Flavonoides/análise , Flavonoides/metabolismo , Mucosa Intestinal/metabolismo , Masculino , Malvaceae/química , Espectrometria de Massas/métodos , Metaboloma , Quercetina/análise , Quercetina/metabolismo , Ratos , Ratos Sprague-Dawley , Insuficiência Renal Crônica/metabolismo
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