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1.
Ann Am Thorac Soc ; 21(3): 393-401, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37962906

ABSTRACT

Rationale: The relationship between symptoms, measured using a validated disease-specific questionnaire, and longitudinal exacerbation risk has not been demonstrated in bronchiectasis. Objectives: The aim of this study is to investigate whether baseline symptoms, assessed using the Quality-of-Life Bronchiectasis Respiratory Symptom Scale (QoL-B-RSS) and its individual component scores, could predict future exacerbation risk in patients with bronchiectasis. Methods: The study included 436 adults with bronchiectasis from three tertiary hospitals. Symptoms were measured using the QoL-B-RSS, with scores ranging from 0 to 100, where lower scores indicated more severe symptoms. We examined whether symptoms as continuous measures were associated with the risk of exacerbation over 12 months. The analysis was also repeated for individual components of the QoL-B-RSS score. Results: The baseline QoL-B-RSS score was associated with an increased risk of exacerbations (rate ratio, 1.25 for each 10-point decrease; 95% confidence interval [CI], 1.15-1.35; P < 0.001), hospitalizations (rate ratio, 1.24; 95% CI, 1.05-1.43; P = 0.02), and reduced time to the first exacerbation (hazard ratio, 1.12; 95% CI, 1.03-1.21; P = 0.01) over 12 months, even after adjusting for relevant confounders, including exacerbation history. The QoL-B-RSS score was comparable to exacerbation history in its association with future frequent exacerbations (defined as three or more exacerbations per year) and hospitalization (area under the curve, 0.86 vs. 0.84; P = 0.46; and area under the curve, 0.81 vs. 0.83; P = 0.41, respectively). Moreover, patients with more severe symptoms in the majority of individual components of the QoL-B-RSS were more likely to experience exacerbations. Conclusions: Symptoms can serve as useful indicators for identifying patients at increased risk of exacerbation in bronchiectasis. Beyond relying solely on exacerbation history, a comprehensive assessment of symptoms could facilitate timely and cost-effective implementation of interventions for exacerbation prevention.


Subject(s)
Bronchiectasis , Quality of Life , Adult , Humans , Prospective Studies , Bronchiectasis/complications , Hospitalization , Tertiary Care Centers
2.
J Sci Food Agric ; 104(3): 1668-1678, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37847204

ABSTRACT

BACKGROUND: Hemp protein isolates (HPIs), which provide a well-balanced profile of essential amino acids comparable to other high-quality proteins, have recently garnered significant attention. However, the underutilized functional attributes of HPIs have constrained their potential commercial applications within the food and agriculture field. This study advocates the utilization of dynamic-high-pressure-microfluidization (DHPM) for the production of stable high-internal-phase emulsions (HIPEs), offering an efficient approach to fully exploit the potential of HPI resources. RESULTS: The findings underscore the effectiveness of DHPM in producing HPI as a stabilizing agent for HIPEs with augmented antioxidant activity. Microfluidized HPI exhibited consistent adsorption and anchoring at the oil-water interface, resulting in the formation of a dense and compact layer. Concurrently, the compression of droplets within HIPEs gave rise to a polyhedral framework, conferring viscoelastic properties and a quasi-solid behavior to the emulsion. Remarkably, HIPEs stabilized by microfluidized HPI demonstrated superior oxidative and storage stability, attributable to the establishment of an antioxidative barrier by microfluidized HPI particles. CONCLUSION: This study presents an appealing approach for transforming liquid oils into solid-like fats using HPI particles, all without the need for surfactants. HIPEs stabilized by microfluidized HPI particles hold promise as emerging food ingredients for the development of emulsion-based formulations with enhanced oxidative stability, thereby finding application in the food and agricultural industries. © 2023 Society of Chemical Industry.


Subject(s)
Cannabis , Emulsions/chemistry , Excipients , Oxidation-Reduction , Antioxidants/metabolism , Oxidative Stress , Particle Size
3.
Front Med (Lausanne) ; 10: 1058001, 2023.
Article in English | MEDLINE | ID: mdl-36824611

ABSTRACT

Background: The high-resolution computed tomography (HRCT) score is an important component of the severity and prognosis score of pulmonary alveolar proteinosis (SPSP). However, the HRCT score in SPSP only considers the extent of opacity, which is insufficient. Methods: We retrospectively evaluated HRCT scores for 231 patients with autoimmune pulmonary alveolar proteinosis (APAP) from three centers of the China Alliance for Rare Diseases. The SPSPII was created based on the overall density and extent, incorporating the SPSP. The severity of APAP patients was assessed using disease severity scores (DSS), SPSP, and SPSPII to determine the strengths and weaknesses of the different assessment methods. We then prospectively applied the SPSPII to patients before treatment, and the curative effect was assessed after 3 months. Results: The HRCT overall density and extent scores in our retrospective analysis were higher than the extent scores in all patients and every original extent score severity group, as well as higher related to arterial partial oxygen pressure (PaO2) than extent scores. The mild patients accounted for 61.9% based on DSS 1-2, 20.3% based on SPSP 1-3, and 20.8% based on SPSPII 1-3. Based on SPSP or SPSPII, the number of severe patients deteriorating was higher in the mild and moderate groups. When applied prospectively, arterial PaO2 differed between any two SPSPII severity groups. The alveolar-arterial gradient in PaO2 (P[A-a]O2), % predicted carbon monoxide diffusing capacity of the lung (DLCO), and HRCT score were higher in the severe group than in the mild and moderate groups. After diagnosis, mild patients received symptomatic treatment, moderate patients received pure whole lung lavage (WLL) or granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy, and severe patients received WLL and GM-CSF therapy. Importantly, the SPSPII in mild and severe groups were lower than baseline after 3 months. Conclusion: The HRCT density and extent scores of patients with APAP were better than the extent score. The SPSPII score system based on smoking status, symptoms, PaO2, predicted DLCO, and overall HRCT score was better than DSS and SPSP for assessing the severity and efficacy and predicting the prognosis. Trial registration: ClinicalTrial.gov, identifier: NCT04516577.

5.
Eur J Clin Microbiol Infect Dis ; 42(2): 141-152, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36469164

ABSTRACT

The aim of this study was to explore the potential mechanisms responsible for the different manifestations of bronchiectasis in patients with pulmonary non-tuberculous mycobacteria (pNTM) infection. We found that the necroptosis level increased significantly after NTM infection. Further, the 31 pNTM-infected patients were classified into two subtypes based on necroptosis-related genes (NRGs) by unsupervised cluster analysis. After that, we compared the differences in clinical parameters, immune cell infiltration, and gene expression between the two subtypes. We observed that the high-necroptosis subtype possessed higher CT scores for bronchiectasis extent (P = 0.008) and severity (P = 0.023). And, more neutrophil infiltration in the high-necroptosis subtype was demonstrated both by the CIBERSORT algorithm and by blood neutrophil count (P = 0.001). Next, 688 differentially expressed genes (DEGs) between two subtypes were identified. To explore the portion in DEGs that might contribute to bronchiectasis, we intersected the DEGs with two gene modules. These two gene modules were identified as the most associated with CT scores for bronchiectasis extent and severity by weighted gene co-expression network analysis (WGCNA). Ninety-three intersection genes were obtained. Finally, 7 hub genes including ACSL1, ANXA3, DYSF, HK3, SLC11A1, STX11, and TLR4 were further screened out by machine learning algorithms and protein-protein interaction network analysis. These results suggested that the differential levels of necroptosis in pNTM patients might lead to differential extent and severity of bronchiectasis on radiographic imaging. This process might be associated with neutrophil infiltration and the involvement of seven hub genes.


Subject(s)
Bronchiectasis , Necroptosis , Humans , Transcriptome , Bronchiectasis/complications , Bronchiectasis/genetics , Algorithms , Nontuberculous Mycobacteria
6.
Brain Behav ; 8(6): e00990, 2018 06.
Article in English | MEDLINE | ID: mdl-29745050

ABSTRACT

PURPOSE: This study examines anesthetic/hypnotic effects of ketamine in AQP4 knockout (KO) and wild-type (WT) mice with the particular focus on neurotransmission. MATERIALS AND METHODS: Ketamine (100 mg/kg) was intraperitoneally injected in 16 WT and 16 KO mice. The hypnotic potencies were evaluated by the loss of the righting reflex (LORR). The amino acids neurotransmitter levels in prefrontal cortex were measured by microdialysis. RESULTS: This study demonstrated that AQP4 knockout significantly shortened the latency compared with WT mice (98.0 ± 4.2 vs. 138.1 ± 15.0 s, p < .05) and prolonged duration of LORR (884.7 ± 58.6 vs. 562.0 ± 51.7 s, p < .05) compared with WT mice in LORR induced by ketamine. Microdialysis showed that lack of AQP4 markedly decreased glutamate level within 20 min (p < .05) and increased γ-aminobutyric acid (GABA) level within 30-40 min (p < .05) after use of ketamine. Moreover, the levels of taurine were remarkably higher in KO mice than in WT mice, but no obvious differences in aspartate were observed between two genotypes. CONCLUSION: AQP4 deficiency led to more susceptibility of mice to ketamine, which is probably due to the modulation of specific neurotransmitters, hinting an essential maintenance of synaptic activity mediated by AQP4 in the action of ketamine.


Subject(s)
Aquaporin 4/deficiency , Excitatory Amino Acid Antagonists/pharmacology , Hypnotics and Sedatives/pharmacology , Ketamine/pharmacology , Amino Acids/metabolism , Animals , Male , Mice, Knockout , Microdialysis/methods , Neurotransmitter Agents/metabolism , Prefrontal Cortex/drug effects , Prefrontal Cortex/metabolism , Reflex, Righting/drug effects , gamma-Aminobutyric Acid
7.
Cancer Med ; 6(5): 1036-1048, 2017 May.
Article in English | MEDLINE | ID: mdl-28401709

ABSTRACT

The biological roles of miRNAs in the development of malignant pleural effusion (MPE) are unclear. In this study, the miRNA microarray analysis was performed in two different prognosis groups of lung adenocarcinoma patients. Expression profiles of miRNAs in MPEs were identified. With the help of quantification PCR, we confirmed the expression differences of miRNAs and further analyzed their biological functions and relative target genes in vitro. The target gene of miR-93 was estimated by online database, and also, the protein was tested. The target gene and the binding sites of specific miRNA were estimated by online database. The combining capacity of binding sites was verified by luciferase reporter gene assay, and the target gene protein was tested by western blot. We detected 107 miRNAs with expression differences (n = 10) and confirmed significant expression differences in miR-93 and miR-146a in two groups of patients (n = 84). By manipulating miR-93 expression of human lymphatic endothelial cells (HLEC) and human umbilical vein endothelial cells (HUVEC), we discovered that high expression of miR-93 inhibited migration, proliferation, and angiogenesis. And also, miR-93 increased not only apoptosis, but also G1 phase cell block. By using luciferase reporter gene assay and western blot, we confirmed that angiopoietin2 (Ang2) was the target of miR-93. The data showed that miR-93 has an inhibiting effect on pleural effusion. By targeting Ang2, miR-93 regulates angiogenesis and lymphangiogenesis and plays a role in pathogenetic mechanism of MPE. MiR-93/Ang2 may shed light on potential new targets in cancer treatment.


Subject(s)
MicroRNAs/genetics , Vesicular Transport Proteins/genetics , 3' Untranslated Regions , Adenocarcinoma , Adenocarcinoma of Lung , Apoptosis , Cell Cycle , Cell Line, Tumor , Cell Movement , Cell Proliferation , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , HEK293 Cells , Human Umbilical Vein Endothelial Cells , Humans , Lung Neoplasms , Male , Oligonucleotide Array Sequence Analysis , Pleural Effusion, Malignant
8.
J Sep Sci ; 40(9): 1928-1941, 2017 May.
Article in English | MEDLINE | ID: mdl-28317248

ABSTRACT

A metabolomics method based on ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry was developed to evaluate the influence of processing times on the quality of raw and processed Polygoni Multiflora Radix. Principal component analysis and partial least-squares discriminant analysis was used to screen the potential maker metabolites that were contributed to the quality changes. Then these marker metabolites were selected as variables in Fisher's discriminant analysis to establish the models that were used to distinguish the raw and processed Polygoni Multiflora Radix in the markets. Additionally, 36 compounds were identified. Twelve raw Polygoni Multiflora Radix samples and 23 processed Polygoni Multiflora Radix samples were distinguished. The results showed that the 12 raw Polygoni Multiflora Radix samples belonged to the group of processing time of 0 h, and two processed Polygoni Multiflora Radix samples were part of the group of processing times of 4 h, 12 samples belonged to group of processing times of 8 to 16 h, and nine samples were the group of processing times of 24 to 48 h. The results demonstrated that the method could provide scientific support for the processing standardization of Polygoni Multiflora Radix.


Subject(s)
Drugs, Chinese Herbal/chemistry , Metabolomics , Polygonum/chemistry , Chromatography, High Pressure Liquid , Mass Spectrometry , Plant Roots/chemistry , Time Factors
9.
J Neurosurg ; 126(1): 45-51, 2017 01.
Article in English | MEDLINE | ID: mdl-27015404

ABSTRACT

OBJECTIVE Large vertebrobasilar fusiform aneurysms (VFAs) represent a small subset of intracranial aneurysms and are often among the most difficult to treat. Current surgical and endovascular techniques fail to achieve a complete or acceptable result because of complications, including late-onset basilar artery thrombosis and perforator infarction. The parallel-stent placement technique was established in the authors' department, and this study reports the application of this technique in the treatment of unruptured VFAs. METHODS Eight patients with 8 unruptured VFAs who underwent parallel stent placement between April 2011 and August 2012 were included. The diameters of the VFAs ranged from 7.9 to 14.0 mm, and the lengths from 27.5 to 54.4 mm. Of the 8 patients with unruptured VFAs, 3 received double or triple parallel stents and 5 patients received a series-connected stent with another 1 or 2 stents deployed parallel to them. Outcomes for these patients were tabulated, based on the modified Rankin Scale (mRS) score and angiographic results. RESULTS All of the 25 stents were successfully placed without any treatment-related complications. During follow-up, 5 patients had decreased mRS scores, 2 were unchanged, and 1 was increased for subarachnoid hemorrhage. Immediate and follow-up clinical outcome was completely or partially recovered in most patients. Follow-up angiograms revealed 2 aneurysms were reduced in size and 6 were unchanged after stent placement. No in-stent stenosis, occlusion of the posterior inferior cerebellar artery, or perforators jailed by the stent occurred in any of the aneurysms. CONCLUSIONS These results provide encouraging support for the parallel-stent placement technique, which can be envisaged as an alternative strategy against unruptured VFAs. However, testing in more patients is needed.


Subject(s)
Basilar Artery/surgery , Intracranial Aneurysm/surgery , Stents , Vertebral Artery/surgery , Adult , Aged , Basilar Artery/diagnostic imaging , Follow-Up Studies , Humans , Intracranial Aneurysm/diagnostic imaging , Male , Middle Aged , Neurosurgical Procedures , Treatment Outcome , Vertebral Artery/diagnostic imaging
11.
Free Radic Biol Med ; 101: 163-175, 2016 12.
Article in English | MEDLINE | ID: mdl-27746262

ABSTRACT

In the pathophysiology of asthma, structural cell dysfunction and concomitant microenvironment changes in airways are crucial to pathological progression, which involves oxidative stress. Caffeic acid phenethyl ester (CAPE) is an active anti-oxidative component obtained from propolis, and has been shown to have beneficial effects on several respiratory disorders, such as chronic obstructive pulmonary disease and lung cancer. However, the impact of CAPE on asthma is not well understood. Therefore, this study investigated the advantages of using CAPE to treat asthma and demonstrated the roles of CAPE in the regulation of airway microenvironments. In ovalbumin (OVA)-sensitized mice, CAPE treatments notably reduced airway hyperresponsiveness, attenuated extensive inflammatory cell infiltration and inhibited goblet cell hyperplasia and collagen deposition and fibrosis. In addition, CAPE improved the airway microenvironment in a dose-dependent manner by inhibiting OVA-induced increases in immunoglobulin E, tumor necrosis factor alpha (TNF-α), transforming growth factor-ß1 (TGF-ß1), interleukin (IL)-4 and IL-13 and suppressing matrix metalloproteinase-9 and alpha-smooth muscle actin expression as well as malondialdehyde production. To determine the underlying mechanisms responsible for these effects, we used TNF-α-stimulated BECs and TGF-ß1-challenged human ASMCs to explore the impacts of CAPE on pro-inflammatory proteins and ASMC proliferation. The results indicated that CAPE significantly limited the secretion of eotaxin-1, monocyte chemoattractant protein-1, IL-8 and intercellular adhesion molecule-1 and dramatically inhibited the proliferation of ASMCs. These effects were shown to be associated with decreased reactive oxidant species (ROS) levels. The phosphorylation of Akt and Mitogen-Activated Protein Kinase (MAPK) caused by increased ROS was significantly decreased by CAPE, which implied a contribution of ROS-MAPK/Akt signaling to the attenuation of asthma. Our findings indicated for the first time that CAPE alleviates airway inflammation and remodeling in chronic asthma by balancing the airway microenvironment, which highlights a novel profile of CAPE as a potent agent for asthma management.


Subject(s)
Anti-Asthmatic Agents/pharmacology , Asthma/drug therapy , Caffeic Acids/pharmacology , Mitogen-Activated Protein Kinases/immunology , Phenylethyl Alcohol/analogs & derivatives , Proto-Oncogene Proteins c-akt/immunology , Reactive Oxygen Species/immunology , Airway Remodeling/drug effects , Airway Remodeling/immunology , Animals , Asthma/chemically induced , Asthma/immunology , Asthma/pathology , Chemokine CCL11/genetics , Chemokine CCL11/immunology , Chemokine CCL2/genetics , Chemokine CCL2/immunology , Female , Gene Expression Regulation , Humans , Immunoglobulin E/genetics , Intercellular Adhesion Molecule-1/genetics , Intercellular Adhesion Molecule-1/immunology , Interleukin-13/genetics , Interleukin-13/immunology , Interleukin-4/genetics , Interleukin-4/immunology , Lung/drug effects , Lung/immunology , Lung/pathology , Mice , Mice, Inbred BALB C , Mitogen-Activated Protein Kinases/genetics , Ovalbumin , Phenylethyl Alcohol/pharmacology , Proto-Oncogene Proteins c-akt/genetics , Reactive Oxygen Species/antagonists & inhibitors , Reactive Oxygen Species/metabolism , Transforming Growth Factor beta1/genetics , Transforming Growth Factor beta1/immunology , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/immunology
12.
Life Sci ; 153: 1-8, 2016 May 15.
Article in English | MEDLINE | ID: mdl-27101925

ABSTRACT

AIMS: Epithelial-mesenchymal transition (EMT) plays a critical role in airway repair and remodeling in many respiratory diseases such as asthma and pulmonary fibrosis. The flavone aglycone, diosmetin, possesses anti-remodeling activity in a murine model of chronic asthma, but little is known about its effects on EMT. Herein, we investigated whether diosmetin inhibits transforming growth factor-ß1 (TGF-ß1)-induced EMT with underlying mechanisms in human bronchial epithelial (HBE) cells. MAIN METHODS: HBE cells were incubated with TGF-ß1 (10ng/ml), either alone or in combination with diosmetin for indicated times. We measured reactive oxygen species (ROS) levels using FACScan and immunofluorescent assays. We assessed protein expression of NADPH oxidase 4 (NOX4), superoxide dismutase (SOD), catalase, Akt, Erk, p38, and phosphorylation levels of Akt, Erk and p38 by Western blot analysis. KEY FINDINGS: TGF-ß1 promoted EMT and ROS generation in HBE cells. Diosmetin significantly suppressed TGF-ß1-induced increases in cell migration and altered N-cadherin, E-cadherin, and α-smooth muscle actin expression. In addition, diosmetin prevented TGF-ß1-induced intracellular ROS generation, down-regulated NOX4, and up-regulated SOD and catalase expression. Furthermore, diosmetin remarkably inhibited TGF-ß1-induced phosphorylation of phosphoinositide 3-kinase (PI3K)/Akt and mitogen activated protein kinase (MAPK) pathways in HBE cells. SIGNIFICANCE: Our results demonstrate for the first time that diosmetin alleviates TGF-ß1-induced EMT by inhibiting ROS generation and inactivating PI3K/Akt and MAPK pathways. Our findings revealed a new role for diosmetin in reducing airway remodeling and fibrogenesis.


Subject(s)
Epithelial-Mesenchymal Transition/physiology , Flavonoids/physiology , MAP Kinase Signaling System , Reactive Oxygen Species/metabolism , Transforming Growth Factor beta1/physiology , Cell Line , Humans , Phosphorylation
13.
Article in English | MEDLINE | ID: mdl-26925151

ABSTRACT

Traditional Chinese medicine (TCM) has been used for the treatment of many complex diseases. However, the bioactive components are always undefined. In this study, a bioactivity-based method was developed and validated to screen lipase inhibitors and evaluate the effects of processing on the lipase inhibitory activity of TCM by ultrahigh performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry and fraction collector (UHPLC/Q-TOF-MS-FC). The results showed that both Polygonum multiflorum and processed P. multiflorum extracts had inhibitory effect against lipase with IC50 values of 38.84 µg/mL and 190.6 µg/mL, respectively. Stilbenes, phenolic acid, flavonoids, and anthraquinones were considered to be the potential lipase inhibitors. Eleven potential lipase inhibitors were simultaneously determined by UHPLC. Principal component analysis (PCA) was employed in exploring the effects of processing time on lipase inhibitory activity of P. multiflorum. Compared with conventional methods, a bioactivity-based method could quantitatively analyze lipase inhibitory activity of individual constituent and provide the total lipase inhibitory activity of the samples. The results demonstrated that the activity integrated UHPLC/Q-TOF-MS-FC method was an effective and powerful tool for screening and identifying lipase inhibitors from traditional Chinese medicines.

14.
Oxid Med Cell Longev ; 2016: 5843672, 2016.
Article in English | MEDLINE | ID: mdl-26783416

ABSTRACT

Asthma is one of the most common inflammatory diseases characterized by airway hyperresponsiveness, inflammation, and remodeling. Morin, an active ingredient obtained from Moraceae plants, has been demonstrated to have promising anti-inflammatory activities in a range of disorders. However, its impacts on pulmonary diseases, particularly on asthma, have not been clarified. This study was designed to investigate whether morin alleviates airway inflammation in chronic asthma with an emphasis on oxidative stress modulation. In vivo, ovalbumin- (OVA-) sensitized mice were administered with morin or dexamethasone before challenge. Bronchoalveolar lavage fluid (BALF) and lung tissues were obtained to perform cell counts, histological analysis, and enzyme-linked immunosorbent assay. In vitro, human bronchial epithelial cells (BECs) were challenged by tumor necrosis factor alpha (TNF-α). The supernatant was collected for the detection of the proinflammatory proteins, and the cells were collected for reactive oxygen species (ROS)/mitogen-activated protein kinase (MAPK) evaluations. Severe inflammatory responses and remodeling were observed in the airways of the OVA-sensitized mice. Treatment with morin dramatically attenuated the extensive trafficking of inflammatory cells into the BALF and inhibited their infiltration around the respiratory tracts and vessels. Morin administration also significantly suppressed goblet cell hyperplasia and collagen deposition/fibrosis and dose-dependently inhibited the OVA-induced increases in IgE, TNF-α, interleukin- (IL-) 4, IL-13, matrix metalloproteinase-9, and malondialdehyde. In human BECs challenged by TNF-α, the levels of proteins such as eotaxin-1, monocyte chemoattractant protein-1, IL-8 and intercellular adhesion molecule-1, were consistently significantly decreased by morin. Western blotting and the 2',7'-dichlorofluorescein assay revealed that the increases in intracellular ROS and MAPK phosphorylation were abolished by morin, implying that ROS/MAPK signaling contributes to the relief of airway inflammation. Our findings indicate for the first time that morin alleviates airway inflammation in chronic asthma, which probably occurs via the oxidative stress-responsive MAPK pathway, highlighting a novel profile of morin as a potent agent for asthma management.


Subject(s)
Flavonoids/therapeutic use , MAP Kinase Signaling System/drug effects , Oxidative Stress/drug effects , Pneumonia/drug therapy , Pneumonia/enzymology , Animals , Bronchi/pathology , Bronchoalveolar Lavage Fluid , Collagen/metabolism , Cytokines/metabolism , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Fibrosis , Flavonoids/pharmacology , Goblet Cells/drug effects , Goblet Cells/pathology , Humans , Hyperplasia , Immunization , Immunoglobulin E/metabolism , Inflammation/pathology , Malondialdehyde/metabolism , Matrix Metalloproteinase 9/metabolism , Mice, Inbred BALB C , Ovalbumin , Pneumonia/pathology , Reactive Oxygen Species/metabolism , Th2 Cells/metabolism , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/pharmacology
15.
J Pharm Biomed Anal ; 117: 1-10, 2016 Jan 05.
Article in English | MEDLINE | ID: mdl-26340557

ABSTRACT

A rapid, sensitive and selective high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of four phenolic acids (neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid and ferulic acid) and seven alkaloids (berberine, epiberberine, coptisine, magnoflorine, berberubine, palmatine and jatrorrhizine) in rat plasma. After mixing with the internal standards tetrahydropalmatine (IS1) and rosmarinic acid (IS2), plasma samples were pretreated by protein precipitation using acetonitrile. The HPLC analysis was performed on an Agilent Eclipse plus C18 (4.6 mm×100 mm, 1.8 µm) column with mobile phase consisting of 0.1% formic acid aqueous solution and acetonitrile at a flow rate of 0.3 mL min(-1). The detection was accomplished for the analytes and internal standards using positive electrospray ionization for the alkaloids and negative electrospray ionization for the phenolic acids in multiple-reaction monitoring mode. The method showed a good linearity over a wide concentration range (r(2)>0.99). The lower limit of quantification of seven alkaloids was lower than 2 ng mL(-1) and that of four phenolic acids was less than 20 ng mL(-1). The developed method was applied to the pharmacokinetic study of 11 components after oral administration of traditional Chinese medicinal preparation Jinqi Jiangtang Tablet in rats.


Subject(s)
Alkaloids/blood , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/analysis , Hydroxybenzoates/blood , Spectrometry, Mass, Electrospray Ionization/methods , Tandem Mass Spectrometry/methods , Administration, Oral , Animals , Chromatography, Liquid/methods , Male , Rats , Rats, Sprague-Dawley , Tablets
16.
Sci Rep ; 5: 11758, 2015 Jul 09.
Article in English | MEDLINE | ID: mdl-26156213

ABSTRACT

Galangin, a natural flavonol, has attracted much attention for its potential anti-inflammatory properties. However, its role in the regulation of airway remodelling in asthma has not been explored. The present study aimed to elucidate the effects of galangin on chronic inflammation and airway remodelling and to investigate the underlying mechanisms both in vivo and in vitro. Ovalbumin (OVA)-sensitised mice were administered with galangin 30 min before challenge. Our results showed that severe inflammatory responses and airway remodelling occurred in OVA-induced mice. Treatment with galangin markedly attenuated the leakage of inflammatory cells into bronchoalveolar lavage fluid (BALF) and decreased the level of OVA-specific IgE in serum. Galangin significantly inhibited goblet cell hyperplasia, collagen deposition and α-SMA expression. Lowered level of TGF-ß1 and suppressed expression of VEGF and MMP-9 were observed in BALF or lung tissue, implying that galangin has an optimal anti-remodelling effect in vivo. Consistently, the TGF-ß1-induced proliferation of airway smooth muscle cells was reduced by galangin in vitro, which might be due to the alleviation of ROS levels and inhibition of MAPK pathway. Taken together, the present findings highlight a novel role for galangin as a promising anti-remodelling agent in asthma, which likely involves the TGF-ß1-ROS-MAPK pathway.


Subject(s)
Airway Remodeling/drug effects , Asthma/metabolism , Asthma/pathology , Flavonoids/pharmacology , Mitogen-Activated Protein Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Reactive Oxygen Species/metabolism , Transforming Growth Factor beta1/metabolism , Actins/metabolism , Animals , Asthma/immunology , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , Cell Proliferation/drug effects , Collagen/metabolism , Disease Models, Animal , Female , Fibrosis , Goblet Cells/metabolism , Goblet Cells/pathology , Humans , Hyperplasia , Immunoglobulin E/blood , Immunoglobulin E/immunology , Matrix Metalloproteinase 9/metabolism , Mice , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/metabolism , Ovalbumin/adverse effects , Oxidation-Reduction/drug effects , Phosphorylation , Signal Transduction/drug effects , Vascular Endothelial Growth Factor A/metabolism
17.
Acta Biochim Biophys Sin (Shanghai) ; 47(8): 604-11, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26033789

ABSTRACT

Bronchial asthma, one of the most common allergic diseases, is characterized by airway hyperresponsiveness (AHR), inflammation, and remodeling. The anti-oxidant flavone aglycone diosmetin ameliorates the inflammation in pancreatitis, but little is known about its impact on asthma. In this study, the effects of diosmetin on chronic asthma were investigated with an emphasis on the modulation of airway remodeling in BALB/c mice challenged with ovalbumin (OVA). It was found that diosmetin significantly relieved inflammatory cell infiltration, goblet cell hyperplasia, and collagen deposition in the lungs of asthmatic mice and notably reduced AHR in these animals. The OVA-induced increases in total cell and eosinophil counts in bronchoalveolar lavage fluid were reversed, and the level of OVA-specific immunoglobulin E in serum was attenuated by diosmetin administration, implying an anti-Th2 activity of diosmetin. Furthermore, diosmetin remarkably suppressed the expression of smooth muscle actin alpha chain, indicating a potent anti-proliferative effect of diosmetin on airway smooth muscle cells (ASMCs). Matrix metallopeptidase-9, transforming growth factor-ß1, and vascular endothelial growth factor levels were also alleviated by diosmetin, suggesting that the remission of airway remodeling might be attributed to the decline of these proteins. Taken together, our findings provided a novel profile of diosmetin with anti-remodeling therapeutic benefits, highlighting a new potential of diosmetin in remitting the ASMC proliferation in chronic asthma.


Subject(s)
Airway Remodeling/drug effects , Asthma/drug therapy , Asthma/physiopathology , Flavonoids/pharmacology , Animals , Anti-Inflammatory Agents/pharmacology , Bronchial Hyperreactivity , Chronic Disease , Disease Models, Animal , Mice , Mice, Inbred BALB C , Ovalbumin/metabolism
18.
J Ethnopharmacol ; 164: 210-22, 2015 Apr 22.
Article in English | MEDLINE | ID: mdl-25698248

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Jinqi Jiangtang Tablet is a traditional Chinese anti-diabetic formula containing three ingredients: Coptis chinensis Franch. (dried rhizome of C. chinensis Franch., Coptis deltoidea C. Y. Cheng et Hsiao and Coptis teeta Wall.), Astragalus membranaceus (Fisch.) Bunge. (dried root of A. membranaceus (Fisch.) Bge. var. mongholicus (Bge. ) Hsiao and A. membranaceus (Fisch.) Bge. ) and Lonicera japonica Thunb. (dried alabastrum or with nascent flowers of L. japonica Thunb. ). Free radicals, α-glucosidase, α-amylase, aldose reductase and lipase are different targets related with diabetes. However, there are no chromatographic methods employed in screening the anti-diabetic compounds from natural products basing on these targets simultaneously. The present study was aimed at the establishment of a multi-targets integrated fingerprinting to clarify the possible mechanism of the action of Traditional Chinese Medicines which simultaneously contained multiple chemical characteristics and effects of constitutions. MATERIALS AND METHODS: The multi-targets integrated fingerprinting was developed and validated to screen anti-diabetic compounds from natural products by using ultra-high-performance liquid chromatography/quadruple-time-of-flight mass spectrometry, fraction collector and microplate reader. Ultra performance liquid chromatography was employed to separate the components in Jinqi Jiangtang Tablet, which were identified by quadruple-time-of-flight mass spectrometry to acquire their structural information and collected by the fraction collector. Finally the active fractions were tested for scavenging 1, 1-diphenyl-2-picrylhydrazyl radical and inhibition of α-glucosidase, α-amylase, aldose reductase, and lipase activities in vitro by microplate reader. RESULTS: Our tests revealed that the Jinqi Jiangtang Tablet showed inhibitory activity against α-glucosidase, α-amylase, aldose reductase and lipase with IC50 values of 0.80 ± 0.02 mg/mL, 1.28 ± 0.13 mg/mL, 0.80 ± 0.02 mg/mL, 1.90 ± 0.18 mg/mL respectively and the scavenging activity with IC50 value of 1.71 ± 0.178 mg/mL. The bioactive fractions were identified to be alkaloids, flavonoids and phenolic acids. The phenolic acids possessed antioxidant activities, namely the scavenging effect on 1, 1-diphenyl-2-picrylhydrazyl rull;). The alkaloids exhibited inhibitory activity against α-glucosidase, aldose reductase, α-amylase, and lipase. The flavonoids also showed mild inhibition on α-glucosidase, aldose reductase, α-amylase and lipase. CONCLUSIONS: The results demonstrate that Jinqi Jiangtang Tablet can scavenge free radicals and inhibit α-glucosidase, aldose reductase, α-amylase and lipase, which may be the possible mechanism of action of Jinqi Jiangtang Tablet for the treatment of diabetes and associated complications. Compared with conventional chromatographic separation and activity assays, the multi-targets integrated fingerprinting, which simultaneously contains the chemical characteristics and multiple effects of constitutions could comprehensively and properly reveal the activity of Jinqi Jiangtang Tablet. The results also show that the multi-targets integrated fingerprinting is a novel and powerful tool for screening and identifying active ingredients from Traditional Chinese Medicines.


Subject(s)
Aldehyde Reductase/antagonists & inhibitors , Drugs, Chinese Herbal/pharmacology , Glycoside Hydrolase Inhibitors/pharmacology , Hypoglycemic Agents/pharmacology , Lipase/antagonists & inhibitors , alpha-Amylases/antagonists & inhibitors , Biphenyl Compounds/chemistry , Drugs, Chinese Herbal/chemistry , Glycoside Hydrolase Inhibitors/chemistry , Hypoglycemic Agents/chemistry , Medicine, Chinese Traditional , Picrates/chemistry , Tablets , alpha-Glucosidases/metabolism
19.
J Food Drug Anal ; 23(2): 267-278, 2015 Jun.
Article in English | MEDLINE | ID: mdl-28911382

ABSTRACT

A method with few markers to determine multicomponents was established and validated to evaluate the quality of Shenfu injection by ultraperformance liquid chromatography coupled with a photodiode array detector. The separations were performed on an ACQUITY UPLC BEH C18 (2.1 × 50 mm2, 1.7 µm) column. Methanol and 0.1% formic acid aqueous solution were used as the mobile phase. The flow rate was 0.3 mL/min. 2 aconitum alkaloids and 12 ginsenosides could be perfectly separated within 15 minutes. Ginsenoside Rg1 and benzoylmesaconine, the easily available active components, were employed as the maker components to calculate the relative correction factors of other components in Shenfu injection, Panax ginseng and Aconitum carmichaeli. The external standard method was also established to validate the feasibility of the method with few markers to determine multicomponents. Parameter p and the principal component analysis method were employed to investigate the disparities among batches for the effective quality control of Shenfu injection. The results demonstrated that the ultraperformance liquid chromatography coupled with a photodiode array detector method with few markers to determine multicomponents could be used as a powerful tool for the quality evaluation of traditional Chinese medicines and their preparations.

20.
J Ethnopharmacol ; 157: 292-308, 2014 Nov 18.
Article in English | MEDLINE | ID: mdl-25281912

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Cuscuta chinensis Lam. has found its use as a traditional medicine in China, Korea, Pakistan, Vietnam, India and Thailand. It is commonly used as an anti-aging agent, anti-inflammatory agent, pain reliever and aphrodisiac. To provide an overview of the ethnopharmacology, phytochemistry, pharmacokinetics, pharmacology and clinical applications of Cuscuta chinensis, as well as being an evidence base for further research works of the plant. MATERIALS AND METHODS: The present review covers the literature available from 1985 to 2014. The information was collected from journals, books, theses and electronic search (Google Scholar, PubMed, ScienceDirect, ESBCO, Springerlink and CNKI). Literature abstracts and full-text articles were analyzed and included in the review. RESULTS: Many phytochemicals have been isolated, identified and published to date, including: at least 18 flavonoids; 13 phenolic acids; 2 steroids; 1 hydroquinone; 10 volatile oils; 22 lignans; 9 polysaccharides; 2 resin glycosides; 16 fatty acids. These phytochemicals and plant extracts exhibit a range of pharmacological activities that include hepatoprotective, renoprotective, antiosteoporotic, antioxidant, anti-aging, antimutagenic, antidepressant, improve sexual function, abortifacient effects, etc. CONCLUSION: This present review offers primary information for further studies of Cuscuta chinensis. The in vitro studies and in vivo models have provided a bioscientific explanation for its various ethnopharmacological uses and pharmacological activities (most notably antioxidant effects) especially in the prevention of hepatic disease and renal failure. It is necessary and important to do more pharmacokinetic and toxicological research works on human subjects in order to inform the possible active compounds in the body and validate its safety in clinical uses.


Subject(s)
Cuscuta/chemistry , Medicine, Traditional , Plant Extracts/pharmacology , Animals , Ethnopharmacology , Humans , Plant Extracts/chemistry , Plant Extracts/pharmacokinetics
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