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1.
J Sep Sci ; 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33475238

RESUMO

Danqi tablet composed of the dried roots of Salvia miltiorrhiza and Panax notoginseng is a well-known Chinese patent medicine commonly used for the treatment of cardio-cerebrovascular diseases such as coronary heart disease and myocardial ischemia. Numerous chemical constituents belonging to S. miltiorrhiza and P. notoginseng were detectable in Danqi tablet. Here, we established and validated a rapid and sensitive ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry method for simultaneous quantification of 23 components in Danqi tablet and then successfully applied to assay 12 batches of samples from ten manufacturers. Our results demonstrated that the contents of 23 components in 12 batches of Danqi tablets varied significantly and their quality indeed existed differently based on the principal component analysis. According to the quantitative data and the loading plot of principal component analysis, five abundant compounds in Danqi tablet were selected as characteristic chemical markers possibly responsible for the quality assessment. Among them, salvianolic acid B and ginsenoside Rg1 were further chosen to be combined at 2:5 ratio to evaluate the anti-thrombotic activity on phenylhydrazine-induced zebrafish heart thrombosis model. Expectedly, this component combination increased the heart red blood cells intensity compared with the model group and the median effective concentration was 123.4 µg/mL, suggestive of its well anti-thrombotic effect. This study contributed to the quantitative evaluation of Danqi tablet and indicated the combination of salvianolic acid B and ginsenoside Rg1 may be capable of reflecting the effect of Danqi tablet, thereby providing a reference for further investigations on the improvement of quality control and clinical application of Danqi tablet.

2.
Diabetes Res Clin Pract ; 171: 108590, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33310125

RESUMO

AIMS: To explore the association between thyroid function and gestational diabetes mellitus (GDM) risk in assisted pregnancies. METHODS: We screened 57,386 pregnant women treated from February 2013 to October 2017, and 2211 patients were retrospectively enrolled, and their data were analyzed based on quintile groups constituted based on serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibody (TPOAb) levels. Odds ratios (ORs) of GDM were analyzed by multivariate logistic regression, adjusted for maternal age and pre-pregnancy body mass index (BMI). RESULTS: The prevalence rate of GDM was 20.1%. Lower FT4 levels were associated with an increased risk of GDM (ORQ2 = 1.512, 95% confidence interval [CI] 1.073-2.132, p = 0.018; ORQ1 = 1.620, 95% CI 1.161-2.261, p = 0.005), but this association disappeared after adjustments. TPOAb+ titer was associated with an increased risk of GDM (aOR = 1.472, 95% CI 1.068-2.028, p = 0.018). Higher TSH (aORQ5 = 2.882, 95% CI 1.919-6.975, p = 0.019) or lower FT4 (aORQ1 = 3.156, 95% CI 1.088-9.115, p = 0.034) levels were associated with an increased risk of GDM in assisted pregnancies for TPOAb+ patients. CONCLUSION: TPOAb+ is an independent risk factor for GDM in patients with assisted pregnancies. Higher TSH or lower FT4 levels, with TPOAb+ detection, are risk factors for GDM in assisted pregnancies.

3.
Talanta ; 224: 121833, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33379051

RESUMO

Cys (Cysteine), Hcy (homocysteine), and GSH (glutathione) are three important kinds of biothiols, playing crucial roles in the variety of pathological and physiological processes. It is greater challenges to simultaneously identify different biothiols due to their similar molecular structures and chemical characteristics. In this work, we employed a multi-emissive fluorescent probe by sulfonyl benzoxadiazole (SBD) with halogen chloride unit as the interaction site based on aromatic substitution-rearrangement strategy to discriminate Cys and Hcy/GSH. The response of probe 1 to Cys would generate FRET and cause a red-shift of fluorescence emission, while Hcy/GSH only lead to different degrees of fluorescence enhancement owing to PET. The probe showed good selectivity, high sensitivity, and low detection limits to three biothiols (Cys: 0.86 µM, Hcy: 0.48 µM and GSH: 0.54 µM). Such capability of the probe could be demonstrated to successfully quantitatively detect the concentrations of Cys/Hcy/GSH in human plasmas. In addition, the probe was also successfully applied for imaging biothiols in lysosomes and real-time monitoring GSH changes in living cells through two-photon fluorescence microscopy.

4.
J Pharm Biomed Anal ; 195: 113828, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33349474

RESUMO

The dried roots of Euphorbia kansui (EK) are especially beneficial for the treatment of edema, but the severe toxicity limits their clinical applications. Euphorbia kansui stir-fried with vinegar (VEK) is traditionally employed to reduce the toxicity of EK. However, the material basis for the toxicity reduction with effectivity conservation is still unclear. Therefore, in this study, a rapid, sensitive, and reliable ultra-fast liquid chromatography tandem mass spectrometry (UFLC-MS/MS) method was firstly established to simultaneously determine six ingenane-type diterpenoids, i.e. kansuiphorin C (1), 5-O-benzoyl-20-deoxyingenol (2), 20-deoxyingenol (3), 3-O-(2'E,4'E-decadienoyl)-20-O-acetylingenol (4), 20-O-(2'E,4'Z-decadienoyl)ingenol (5), and ingenol (6), in EK and VEK based on the processing conversion. Then, the toxicity evaluation on zebrafish embryos and modulation of the expression of aquaporin-3 (AQP3) proteins in HT-29 cells were employed to investigate the toxicity-activity of six compounds. Chromatographic separation was obtained on Waters BEH RP18 column (2.1 mm × 100 mm, 2.5 µm) with the mobile phase composed of 0.1 % formic acid in acetonitrile and water, respectively. The column temperature was 35 ℃ at a flow rate of 0.4 mL min-1. Multiple reaction monitoring was conducted in both positive and negative modes for quantitative analysis. The method was then successfully used for the determination of six compounds in EK and VEK. In addition, 1, 2, 4, and 5 had evident cardiotoxicity, intestinal irritation and nutrient absorption disorders on zebrafish larvae, while no in-vivo toxicity was seen for groups given 3 and 6 (LC50 > 200 µM). Meanwhile, 1, 2, 4, 5, and 6 significantly increased the expression of AQP3 protein (p < 0.05) to promote the excretion of water in the colon. This study demonstrated that toxic ingenane-type diterpenoids converted into the less toxic compounds with the same core structure through the breakage of multiple ester bonds in the side chain. At the same time, the laxative effect was retained, providing useful information for the optimization of the process of EK and quality evaluation of other similar toxic Chinese herbal medicines.

5.
Brain Behav ; : e01995, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33300684

RESUMO

Leonurus japonicus Houtt., a traditional Chinese herbal medicine, is often used as a gynecological medicine with the effect of promoting blood circulation, regulating menstruation, clearing heat, and detoxificating. As the most important alkaloid in L. japonicus, leonurine has a wide range of biological activities, such as antioxidation, anti-inflammation, and anti-apoptosis. Cardiovascular system and central nervous system diseases are arrogant killers that threaten human lives and health around the world, but many drugs for treating them have certain side effects. This paper reviews the potential therapeutic effects of leonurine on cardiovascular system and central nervous system diseases, summarizes the previous research progress, and focuses on its therapeutic effect in various diseases. Although leonurine plays a prominent role in the treatment of cardiovascular system and central nervous system diseases, there are still some shortages, such as low bioavailability, weak transmembrane ability, and poor fat solubility. Therefore, the structure modification of leonurine may solve these problems and provide reference value for the development of new drugs. At present, leonurine is in clinical trial, and it is hoped that our summary will help to provide guidance for its future research on the basic science and clinical application.

6.
J Ethnopharmacol ; : 113583, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33189845

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Shizaotang (SZT), consisted of Euphorbia kansui S.L.Liou ex S.B.Ho (EK), Euphorbia pekinensis Rupr. (EP), Daphne genkwa Sieb. et Zucc. (DG,fried) and Ziziphus jujuba Mill. (ZJ), is usually used for treating malignant pleural effusions (MPE), but the toxicity of EK and EP limits its clinical safe application. It was reported that vinegar processing can reduce the toxicity of EK and EP. Whether EK and EP processing with vinegar can cause the reduced toxicity and retained pharmacological effects of SZT, it still remains unknown. AIM OF THE STUDY: We aimed to evaluate whether using vinegar processed EK and EP would reduce toxicity and preserve water expelling effect of SZT. MATERIALS AND METHODS: Network pharmacology and qualitative analysis of SZT/VSZT were used to construct compound-target-pathway network of their effects and toxicity. Pleural fluid weight, urine volume, uric electrolyte, pH, pro-inflammatory cytokines in pleural fluid, serum Renin-Angiotensin-Aldosterone System (RAAS), anti-diuretic hormone (ADH) and intestinal aquaporin 8 (AQP8) protein were used to evaluate the effect mechanisms involved in rats experiments. And liver damage, oxidative damage and HE staining (liver, stomach, and intestine) were used to determine the toxicity. RESULTS: Network pharmacology analysis reviewed inflammation-related pathways of the effect and toxicity of SZT/VSZT: VEGF-PI3K-AKT pathway inhibited MPE by changing the vasopermeability; PI3K-Akt/Mitogen-activated protein kinase (MAPK)/TNF-NF-κB signaling pathway inhibited MPE by up-regulating expression of AQP8 protein. In vivo experiments displayed that SZT/VSZT could reduce pleural fluid, increase urine volume, lower pro-inflammatory cytokines levels and up-regulate AQP8 protein expression significantly (P < 0.05, P < 0.01). In addition, disorders on electrolyte (Na+, K+ and Cl-) and pH were ameliorated (P < 0.05, P < 0.01). The levels of RAAS and ADH were significantly dose-dependently called back (P < 0.01). These findings were partly consistent with the results of network pharmacology analysis. Results of toxicity experiments demonstrated that SZT and VSZT exhibited certain toxicity on normal rats, and VSZT had lower toxicity than that of SZT. Interestingly, SZT and VSZT exerted alleviation effect to the liver damage and oxidative damage on model rats. CONCLUSION: SZT/VSZT improved MPE by regulating associated inflammation pathways. Besides, compared to SZT, VSZT showed lower toxicity and equivalent expelling MPE effect. This study may provide scientific basis for guiding the clinical application of SZT.

7.
Brief Bioinform ; 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33253353

RESUMO

The outbreak and pandemic of SARS-CoV-2 in 2019 has caused a severe public health burden and will challenge global health for the future. The discovery and mechanistic investigation of drugs against Coronavirus disease 2019 (COVID-19) is in deadly demand. The paper published by Li and colleagues proposed the hypothesis that vitamin C combined with glycyrrhizic acid in treating COVID-19 and its mechanistic investigation was performed by a database-based network pharmacology. In this letter, we present critical comments on the limitations and insufficiencies involved, from both the perspective of network pharmacology and current evidence on COVID-19.

8.
J Ethnopharmacol ; : 113507, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33098970

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Malignant ascites (MA) effusion is mainly caused by hepatocellular, ovarian, and breast cancer etc. It has been reported that Euphorbia kansui (EK), the root of Euphorbia kansui S.L.Liou ex S.B.Ho, possessing a therapeutic effect on MA. However, the clinical applications of EK are seriously restricted for its severe toxicity. Although studies demonstrated that vinegar-processing can reduce the toxicity and retain the water expelling effect of EK, its specific mechanism remains unknown. AIM OF THE STUDY: This study aims to explore the underlying mechanisms of toxicity reduction without compromising the pharmacological effects of EK stir-fried with vinegar (VEK). MATERIALS AND METHODS: 3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol (3-O-EZ), a major diterpenoid of EK, could convert into ingenol after processing EK with vinegar. The H22 mouse hepatoma ascites model was replicated, and were given 3-O-EZ and ingenol seven days (110.14, 50.07 and 27.54 mg/kg). The histopathological observation, serum liver enzymes, serum Renin-Angiotensin-Aldosterone System (RAAS) levels, ascites volumes, pro-inflammatory cytokines levels and H22 cells apoptosis in ascites were examined. Then the intestine (Aquaporin 8, AQP8) and kidney (Aquaporin 2, AQP2; Vasopressin type 2 receptor, V2R) protein expression were detected, as well as the metabolomics of serum were analyzed. Finally, the content of 3-O-EZ and ingenol in EK and VEK were investigated. RESULTS: 3-O-EZ and ingenol can relieve hepatic and gastrointestinal injuries, reduce ascites volumes, enhance the H22 cells apoptosis, ameliorate abnormal pro-inflammatory cytokines and RAAS levels, and down-regulate the expression of AQP8, AQP2, V2R. The involved metabolic pathways mainly included glycerophospholipid metabolism and arachidonic acid metabolism. And the decreasing rate of 3-O-EZ in VEK was 19.14%, the increasing rate of ingenol in VEK was 92.31%. CONCLUSION: 3-O-EZ and ingenol possess significant effect in treating MA effusion, while ingenol has lower toxicity compared with 3-O-EZ. And provide evidence for the mechanism of attenuation in toxicity without compromising the pharmacological effects of VEK.

9.
Front Pharmacol ; 11: 01265, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33117148

RESUMO

The incidence rate of cardio-cerebrovascular diseases (CCVDs) is increasing worldwide, causing an increasingly serious public health burden. The pursuit of new promising treatment options is thus becoming a pressing issue. Hydroxysafflor yellow A (HSYA) is one of the main active quinochalcone C-glycosides in the florets of Carthamus tinctorius L., a medical and edible dual-purpose plant. HSYA has attracted much interest for its pharmacological actions in treating and/or managing CCVDs, such as myocardial and cerebral ischemia, hypertension, atherosclerosis, vascular dementia, and traumatic brain injury, in massive preclinical studies. In this review, we briefly summarized the mode and mechanism of action of HSYA on CCVDs based on these preclinical studies. The therapeutic effects of HSYA against CCVDs were presumed to reside mostly in its antioxidant, anti-inflammatory, and neuroprotective roles by acting on complex signaling pathways.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33029181

RESUMO

The present study aims to investigate the roles of herb pairs containing Angelicae Sinensis Radix (Danggui) in Xin-Sheng-Hua Granule (XSHG) on hemolytic and aplastic anemia (HAA) mice. HAA model mice were induced by acetyl phenylhydrazine and cyclophosphamide; then the samples of XSHG and its decomposed recipes (DY, DC, DT, DH, DJ, and DZ) were orally administrated to these mice. Indicators of peripheral blood routine, organ index, and ATPase activities were tested. Moreover, the main effective components in these samples were also analyzed by UHPLC-TQ-MS/MS. Clear separation between the control and model groups from score plot of principal component analysis (PCA) was easily seen, indicating that HAA model was successfully conducted. Afterwards, relative distance calculation method between dose groups and control group from PCA score plot was adopted to evaluate the integrated effects of hematinic function of different samples. And the orders of hematinic effects were as follows: XHSG > DJ > DT > DZ > DH > DC > DY. Further analysis of these samples by UHPLC-TQ-MS/MS revealed that XSHG underwent complicated changes when herb pairs containing Danggui were excluded from XSHG, respectively. Compared with XSHG, the vast majority of active compounds in sample DY (formula minus herb pair Danggui-Yimucao) decreased significantly, which could partly explain why herb pair Danggui-Yimucao made great contribution to XSHG. These findings showed that withdrawal analysis method is a valuable tool to analyze the impacts of herb pairs containing Danggui on XSHG, which could lay foundation to reveal the compatibility rules of this formula.

11.
J Pharm Biomed Anal ; 191: 113638, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32980794

RESUMO

Rubiae Radix et Rhizoma (called "Qiancao", QC), the root and rhizome of Rubia cordifolia L., has been widely used in clinical practice for its excellent performance in removing blood stasis and haemostasis. However, after carbonization processing, significant changes occurred in chemical components of the charcoal of Rubiae Radix et Rhizoma (called "Qiancaotan", QCT), which enhanced the performance in haemostasis and weakened the performance in removing blood stasis in clinic. In order to study the material basis of function variation during processing, a rapid, reliable, accurate and validated UPLC-MS/MS approach was established to determine twelve quinones in QC and QCT simultaneously. Meanwhile, the antithrombotic effect of target components on zebrafish thrombus model induced by phenylhydrazine (PHZ) was investigated. Chromatographic separation was accomplished on an ACQUITY UPLC C18column with acetonitrile-water containing 0.2 % (v/v) formic acid as mobile phase, at a flow rate of 0.30 mL/min. Quantitation was performed using multiple reaction monitoring (MRM) in positive and negative ion electrospray ionization (ESI). Furthermore, the activity evaluation studies showed that the reduction of removing blood stasis effect of QCT was due to the decrease of dehydro-α-lapachone, lapachol, rubioncolin C and mollugin. This study demonstrated that the method has been successfully applied to determine the content of twelve quinones responsible for the function variation of QCT, and provided a new insight into the material basis and the effect of eliminating stasis before and after processing of QC.

12.
Ther Adv Chronic Dis ; 11: 2040622320944802, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32843956

RESUMO

Aims: Interstitial lung disease (ILD) is the most common type of pulmonary involvement of extraglandular complication in patients with primary Sjögren's syndrome (pSS), but the diagnosis of pSS-associated ILD (pSS-ILD) is still challenging. This study aimed to investigate the levels of serum tumor markers in pSS patients with or without ILD (pSS-non-ILD) and explore its diagnostic value for pSS-ILD. Methods: A total of 168 pSS-ILD patients and age- and sex-matched 538 pSS-non-ILD were recruited. The levels of peripheral tumor markers, including carbohydrate antigen (CA)153, CA125, CA19-9, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), ß-human chorionic gonadotropin, alpha fetoprotein, CA724, and complexed prostate specific antigen, the clinical manifestations, and general laboratory indicators were measured and collected. Results: Compared with pSS-non-ILD, pSS-ILD patients had higher levels of disease activity indicators, such as EULAR Sjögren's syndrome disease activity index, ESR, and CRP, and elevated serum levels of tumor markers: NSE, CEA, CA125, and CA153. The serum levels of CA153 [odds ratio (OR) = 4.521, 95% confidence interval (CI) = [1.871, 10.928)] and CEA [OR = 2.879, 95% CI = (1.305, 6.353)] were significantly correlated with the onset of SS-ILD. CA153 was the only tumor marker with area under receiver operating characteristic curve (AUC) over 0.7 [AUC = 0.743, 95% CI = (0.70, 0.79)]. Conclusion: Tumor markers increased in serum of pSS-ILD patients. Higher CA153 levels are significantly correlated to the increased risk of ILD in patients with pSS and may be directly involved in the pathogenesis of pSS-ILD. Serum CA153 had the best diagnostic value in those tumor markers for pSS-ILD without malignancy.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32802140

RESUMO

Objective: To systematically evaluate the efficacy of Chinese herbal medicine Qiju Dihuang Decoction (QDD) for hypertension. Methods: A comprehensive literature search of randomized controlled trials using QDD to treat hypertension was conducted in 7 electronic databases, including Chinese databases. Subjects and abstracts of the trials were read in NoteExpress for preliminary screening, and the full text was read for further screening. The data extraction table was made for the selected 19 trials, and risk of bias was assessed by using the Cochrane collaboration tool, followed by data analysis using Rev Man 5.3. Results: The antihypertensive efficacy of QDD is 1.45 times that of antihypertensive drugs and 1.56 times that of conventional therapies, which can also reduce the endothelin level. QPAD exhibits an antihypertensive effect, and its clinical efficacy is 1.34 times and 1.61 times that of antihypertensive drugs, which can not only significantly lower the diastolic blood pressure but also reduce the 24 h mean ambulate blood pressure. At the same time, it can decrease the TCM syndrome score, inhibit the inflammation, protect the renal function, reduce the insulin resistance, and improve the life quality of patients. Conclusion: QDD can effectively reduce blood pressure and improve the life quality of patients with hypertension, which plays a certain role in preventing hypertension complications. However, due to the methodological deficiencies, more rigorous randomized controlled trials will be needed in the future to provide stronger evidence.

14.
J Ethnopharmacol ; 261: 113000, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-32663590

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui Buxue Decoction (DBD), as a classical Chinese medicine prescription, is composed of Danggui (DG) and Huangqi (HQ) at a ratio of 1:5, and it has been used clinically in treating anemia for hundreds of years. AIM OF THE STUDY: The aim of this study was to explore the treatment mechanisms of DBD in anemia rats from the perspective of thymus and spleen. MATERIALS AND METHODS: In this study, a successful hemorrhagic anemia model was established, and metabolomics (UPLC-QTOF-MS/MS) and proteomics (label-free approach) together with bioinformatics (Gene Ontology analysis and Reactome pathway enrichment), correlation analysis (pearson correlation matrix) and joint pathway analysis (MetaboAnalyst) were employed to discover the underlying mechanisms of DBD. RESULTS: DBD had a significant blood enrichment effect on hemorrhagic anemia rats. Metabolomics and proteomics results showed that DBD regulated a total of 10 metabolites (lysophosphatidylcholines, etc.) and 41 proteins (myeloperoxidase, etc.) in thymus, and 9 metabolites (L-methionine, etc.) and 24 proteins (transferrin, etc.) in spleen. With GO analysis and Reactome pathway enrichment, DBD mainly improved anti-oxidative stress ability of thymocyte and accelerated oxidative phosphorylation to provide ATP for splenocyte. Phenotype key indexes were strongly and positively associated with most of the differential proteins and metabolites, especially nucleosides, amino acids, Fabp4, Decr1 and Ndufs3. 14 pathways in thymus and 9 pathways in spleen were obtained through joint pathway analysis, in addition, the most influential pathway in thymus was arachidonic acid metabolism, while in spleen was the biosynthesis of phenylalanine, tyrosine and tryptophan. Furthermore, DBD was validated to up-regulate Mpo, Hbb and Cp levels and down-regulate Ca2+ level in thymus, as well as up-regulate Fabp4, Ndufs3, Tf, Decr1 and ATP levels in spleen. CONCLUSION: DBD might enhance thymus function mainly by reducing excessive lipid metabolism and intracellular Ca2+ level, and promote ATP production in spleen to provide energy.

15.
J Ethnopharmacol ; 260: 113050, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-32502651

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Neuropathic pain, the incidence of which ranges from 5 to 8% in the general population, remains challenge in the treatment. Shaoyao Gancao decoction (SGD) is a Chinese classical formula used to relieve pain for thousands of years and has been applied for neuropathic pain nowadays. However, the effective components of SGD for the treatment of neuropathic pain remains unclear. AIMS OF STUDY: To investigate the effect and potential mechanism of SGD against neuropathic pain and further reveal the effective components of SGD in the treatment of neuropathic pain. MATERIALS AND METHODS: Spared nerve injury (SNI) model rats of neuropathic pain were orally given SGD to intervene, the components in vivo after SGD administration were determined, behavior indicators, biochemical parameters, and metabolomics were applied for assessing the efficacy. Then correlation between components and biomarkers was analyzed by pearson correlation method. To further measure the contribution of components to efficacy, the combination of partial least-squares regression (PLSR) and multi-index comprehensive method was carried out, according to the corresponding contribution degree of the results, the components with large contribution degree were considered as the effective components. RESULTS: SGD exhibited a significant regulatory effect on neuropathic pain, which could increase the pain threshold and decrease the levels of SP, ß-EP, PGE2 and NO. With the high resolution of UPLC-Q-TOF/MS technology, a total of 128 compounds from SGD were identified and 44 of them were absorbed in blood. Besides, 40 serum biomarkers were identified after intervention of SGD and the metabolic pathways were constructed. The key metabolic pathways including Glycerophospholipid metabolism, Linoleic acid metabolism, Alpha-linolenic acid metabolism, Glycosylphosphatidylinositol-anchor biosynthesis and Arachidonic acid metabolism may be related to the regulation of neuropathic pain. Metabolomics combined with PLSR and multi-index comprehensive method was utilized to discover 5 components including paeonol, DL-Arabinose, benzoic acid, hispaglabridin A and paeonilactone C as effective components of SGD in the treatment of neuropathic pain. This strategy was used to explore the effective components of SGD and elucidate its possible analgesic mechanism. CONCLUSION: This study demonstrate that SGD significantly relieved neuropathic pain and elucidated the effective components of SGD for treating neuropathic pain, the strategy as an illustrative case study can be applied to other classical formula and is beneficial to improve the quality and efficacy.

16.
J Sep Sci ; 43(16): 3170-3182, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32506800

RESUMO

Safflower has both medicinal and edible values but research on its nutrient composition is still lacking. This study was established for the quantitative determination of 28 nucleosides, nucleobases, and amino acids based on the ultra-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry. Analysis of 30 batches of safflower from different producing areas indicated that the contents of l-proline, l-asparagine, l(+)-arginine, l-serine, l-histidine, uracil, guanosine, and uridine was high in safflower. Principle component analysis and cluster analysis found that samples from different regions could be distinguished well, and samples from the same area could be clustered into one class, different geographical environments may cause the differences of nucleosides, nucleobases, and amino acids in safflower. The analysis of principal component analysis, cluster analysis, and counter propagation artificial neural network show similar results. Then the content of nucleosides, nucleobases, and essential amino acids were compared, and found that the content in safflower from Gansu was higher than those from other regions, and there was a little difference between the samples from Xinjiang, Sichuan, and Yunnan. This research revealed the composition of nucleosides, nucleobases, and amino acids in safflower, and provided a theoretical basis for utilization of safflower.

18.
J Physiol ; 598(13): 2719-2739, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32306402

RESUMO

KEY POINTS: Muscle-derived neurotrophic factors may offer therapeutic promise for treating neuromuscular diseases. We report that a muscle-derived neurotrophic factor, BDNF, rescues synaptic and muscle function in a muscle-type specific manner in mice modelling Kennedy's disease (KD). We also find that BDNF rescues select molecular mechanisms in slow and fast muscle that may underlie the improved cellular function. We also report for the first time that expression of BDNF, but not other members of the neurotrophin family, is perturbed in muscle from patients with KD. Given that muscle BDNF had divergent therapeutic effects that depended on muscle type, a combination of neurotrophic factors may optimally rescue neuromuscular function via effects on both pre- and postsynaptic function, in the face of disease. ABSTRACT: Deficits in muscle brain-derived neurotrophic factor (BDNF) correlate with neuromuscular deficits in mouse models of Kennedy's disease (KD), suggesting that restoring muscle BDNF might restore function. To test this possibility, transgenic mice expressing human BDNF in skeletal muscle were crossed with '97Q' KD mice. We found that muscle BDNF slowed disease, doubling the time between symptom onset and endstage. BDNF also improved expression of genes in muscle known to play key roles in neuromuscular function, including counteracting the expression of neonatal isoforms induced by disease. Intriguingly, BDNF's ameliorative effects differed between muscle types: synaptic strength was rescued only in slow-twitch muscle, while contractile strength was improved only in fast-twitch muscle. In sum, muscle BDNF slows disease progression, rescuing select cellular and molecular mechanisms that depend on fibre type. Muscle BDNF expression was also affected in KD patients, reinforcing its translational and therapeutic potential for treating this disorder.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32190085

RESUMO

Background: Qixuehe capsule (QXH), a Chinese patent medicine, has been demonstrated to be effective in the treatment of menstrual disorders. In traditional Chinese medicine (TCM) theory, qi stagnation and blood stasis syndrome (QS-BSS) is the main syndrome type of menstrual disorders. However, the pharmacodynamic effect of QXH in treating QS-BSS is not clear, and the main active compounds and underlying mechanisms remain unknown. Methods: A rat model of QS-BSS was established to evaluate the pharmacodynamic effect of QXH. Thereafter, a network pharmacology approach was performed to decipher the active compounds and underlying mechanisms of QXH. Results: QXH could significantly reduce the rising whole blood viscosity (WBV) and plasma viscosity (PV) but also normalize prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB) content in QS-BSS rats. Based on partial least-squares-discriminant analysis (PLS-DA), the low-dose QXH-intervened (QXH-L) and the high-dose QXH-intervened (QXH-H) groups seemed the most effective by calculating the relative distance to normality. Through network pharmacology, QXH may improve hemorheological abnormality mainly via 185 compounds-51 targets-28 pathways, whereas 184 compounds-68 targets-28 pathways were associated with QXH in improving coagulopathy. Subsequently, 25 active compounds of QXH were verified by UPLC-Q/TOF-MS. Furthermore, 174 active compounds of QXH were shared in improving hemorheological abnormality and coagulopathy in QS-BSS, each of which can act on multiple targets to be mainly involved in complement and coagulation cascades, leukocyte transendothelial migration, PPAR signaling pathway, VEGF signaling pathway, and arachidonic acid metabolism. The attribution of active compounds indicated that Angelicae Sinensis Radix (DG), Paeoniae Radix Rubra (CS), Carthami Flos (HH), Persicae Semen (TR), and Corydalis Rhizoma (YHS) were the vital herbs of QXH in treating QS-BSS. Conclusion: QXH can improve the hemorheology abnormality and coagulopathy of QS-BSS, which may result from the synergy of multiple compounds, targets, and pathways.

20.
Anal Chim Acta ; 1107: 74-84, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32200904

RESUMO

A sensitive, rapid, precise and specific analytical method of hydrophilic interaction ultra-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry (HILIC-UHPLC-QTRAP®/MS2) combined with a high-efficiency and easy sample preparation technology of ultrasound-assisted ionic liquid dispersive liquid-liquid microextraction (UA-IL-DLLME) was developed to investigate neurotransmitters (NTs) in mild cognitive impairment, mild dementia and moderate dementia patients' urine samples. Firstly, the UA-IL-DLLME parameters were optimized using Plackett-Burman screening and rotatable central composite design, and the main optimal conditions were obtained: ultrasound power of 307 W, ultrasound time of 4.3 min and agitation time of 4.8 min. Secondly, HILIC-UHPLC-QTRAP®/MS2 method was developed to simultaneously determine 15 underivatized NTs in urine samples. The analysis results of clinical samples showed that some NTs such as γ-aminobutyric acid (GABA), acetylcholine (Ach) and glutamic acid (Glu) presented significant differences in different dementia stages. Finally, multivariate analysis based on the combination of principal component analysis and supervised counter propagation artificial neural network was developed for comprehensive analysis of the obtained clinical data sets. As a result, GABA and Glu were simultaneously presented meaningful contribution for classification of samples, and might be considered as potential differential compounds to the urine samples from cluster patients with different dementia stages. In summary, the presented strategy of preparation, analysis and statistics might be used to investigate NTs in different clinical biological fluids.

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