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1.
Pharmacol Res ; : 106083, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35033647

RESUMO

The pathogenic hyper-inflammatory response has been revealed as the major cause of the severity and death of the Corona Virus Disease 2019 (COVID-19). Xuanfei Baidu Decoction (XFBD) as one of the "three medicines and three prescriptions" for the clinically effective treatment of COVID-19 in China, shows unique advantages in the control of symptomatic transition from moderate to severe disease states. However, the roles of XFBD to against hyper-inflammatory response and its mechanism remain unclear. Here, we established acute lung injury (ALI) model induced by lipopolysaccharide (LPS), presenting a hyperinflammatory process to explore the pharmacodynamic effect and molecular mechanism of XFBD on ALI. The in vitro experiments demonstrated that XFBD inhibited the secretion of IL-6 and TNF-α and iNOS activity in LPS-stimulated RAW264.7 macrophages. In vivo, we confirmed that XFBD improved pulmonary injury via down-regulating the expression of proinflammatory cytokines such as IL-6, TNF-α and IL1-ß as well as macrophages and neutrophils infiltration in LPS-induced ALI mice. Mechanically, we revealed that XFBD treated LPS-induced acute lung injury through PD-1/IL17A pathway which regulates the infiltration of neutrophils and macrophages. Additionally, one major compound from XFBD, i.e. glycyrrhizic acid, shows a high binding affinity with IL17A. In conclusion, we demonstrated the therapeutic effects of XFBD, which provides the immune foundations of XFBD and fatherly support its clinical applications.

2.
J Ethnopharmacol ; 283: 114701, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34606948

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Xuanfei Baidu Decoction (XFBD), one of the "three medicines and three prescriptions" for the clinically effective treatment of COVID-19 in China, plays an important role in the treatment of mild and/or common patients with dampness-toxin obstructing lung syndrome. AIM OF THE STUDY: The present work aims to elucidate the protective effects and the possible mechanism of XFBD against the acute inflammation and pulmonary fibrosis. METHODS: We use TGF-ß1 induced fibroblast activation model and LPS/IL-4 induced macrophage inflammation model as in vitro cell models. The mice model of lung fibrosis was induced by BLM via endotracheal drip, and then XFBD (4.6 g/kg, 9.2 g/kg) were administered orally respectively. The efficacy and molecular mechanisms in the presence or absence of XFBD were investigated. RESULTS: The results proved that XFBD can effectively inhibit fibroblast collagen deposition, down-regulate the level of α-SMA and inhibit the migration of fibroblasts. IL-4 induced macrophage polarization was also inhibited and the secretions of the inflammatory factors including IL6, iNOS were down-regulated. In vivo experiments, the results proved that XFBD improved the weight loss and survival rate of the mice. The XFBD high-dose administration group had a significant effect in inhibiting collagen deposition and the expression of α-SMA in the lungs of mice. XFBD can reduce bleomycin-induced pulmonary fibrosis by inhibiting IL-6/STAT3 activation and related macrophage infiltration. CONCLUSIONS: Xuanfei Baidu Decoction protects against macrophages induced inflammation and pulmonary fibrosis via inhibiting IL-6/STAT3 signaling pathway.


Assuntos
COVID-19/tratamento farmacológico , Medicamentos de Ervas Chinesas , Inflamação/tratamento farmacológico , Macrófagos/efeitos dos fármacos , SARS-CoV-2 , Transdução de Sinais/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Fibroblastos/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes , Humanos , Interleucina-6/antagonistas & inibidores , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células NIH 3T3 , Fitoterapia , Fibrose Pulmonar/patologia , Fibrose Pulmonar/prevenção & controle , Células RAW 264.7 , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo
3.
Virus Res ; 307: 198605, 2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-34662681

RESUMO

Japanese encephalitis virus (JEV) causes the most commonly diagnosed viral encephalitis in Asia. JEV is a highly neurotropic flavivirus that can replicate efficiently in the brain. Axl belongs to the TAM (Tyro3, Axl, Mer) family, a group of tyrosine kinase receptors involved in the viral entry, micked as apoptotic bodies and regulation of innate immunity. However, the underlying mechanisms on its regulation in the neurons for JEV are unclear. Here, we found that Axl was upregulated in neurons after JEV infection. Unexpectedly, Axl deficient (Axl-/-) mice were more susceptible to JEV infection with increased viral loads in neurons. The RNA-sequencing analysis between the wild type neurons and Axl-/- neurons infected with JEV showed that many interferon-stimulated genes were downregulated in the Axl-/- neurons which innate immunity was attenuated largely. The rescue experiment in Axl-/- neurons indicated that Axl may be positively involved in the regulation of antiviral immunity. Taken together, our data demonstrated that Axl may play an antiviral role in JEV replication within neurons by modulating neuronal innate immunity.

4.
J Chem Phys ; 155(22): 224301, 2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34911308

RESUMO

In an effort to extend the cold gas phase spectroscopic database of the cyclic formic acid dimer (FAD), we present and analyze the jet-cooled vibrational infrared and Raman spectrum of (HCOOH)2 in the monomer fingerprint region between 600 and 1500 cm-1. The present study bridges the gap between the intermolecular dimerization-induced and the carbonyl stretching fundamentals that have already been reexamined using jet-cooled or high-resolution spectroscopy. This completes the characterization of the jet-cooled vibrational (HCOOH)2 spectrum below the complex OH (CH) stretching fundamentals, and we report resonance-induced FAD combination/overtone transitions that will serve as a valuable reference for a theoretical modeling of its vibrational dynamics. As a by-product, several new formic acid trimer fundamentals are identified in the jet spectra and assigned with the help of second-order vibrational perturbation theory (VPT2). The polar formic acid dimer still eludes detection in a supersonic jet, but we are able to estimate an experimental upper-bound of the polar dimer-to-trimer-to-cyclic dimer intensity ratio to about 1:10:100 under typical expansion conditions. Using VPT2 with resonance treatment (VPT2+K), we reinvestigate the notorious ν22 resonance triad. Generally, we find that VPT2, which is, of course, inadequate for modeling the resonance-rich OH stretching spectrum of FAD, is performing very satisfactorily in predicting fundamental and two-quantum state term values for the slower modes below 1500 cm-1. As these modes are the building blocks for the ultrafast energy dissipation in the OH stretching region, the present work opens the door for its quantitative understanding.

5.
Front Pharmacol ; 12: 720873, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899290

RESUMO

Pulmonary arterial hypertension (PAH) is characterized by pulmonary artery remodeling that may subsequently culminate in right heart failure and premature death. Although there are currently both non-pharmacological (lung transplantation, etc.) and pharmacological (Sildenafil, Bosentan, and new oral drugs on trial) therapies available, PAH remains a serious and fatal pulmonary disease. As a unique medical treatment, traditional herbal medicine (THM) treatment has gradually exerted its advantages in treating PAH worldwide through a multi-level and multi-target approach. Additionally, the potential mechanisms of THM were deciphered, including suppression of proliferation and apoptosis of pulmonary artery smooth muscle cells, controlling the processes of inflammation and oxidative stress, and regulating vasoconstriction and ion channels. In this review, the effects and mechanisms of the frequently studied compound THM, single herbal preparations, and multiple active components from THM are comprehensively summarized, as well as their related mechanisms on several classical preclinical PAH models. It is worth mentioning that sodium tanshinone IIA sulfonate sodium and tetramethylpyrazine are under clinical trials and are considered the most promoting medicines for PAH treatment. Last, reverse pharmacology, a strategy to discover THM or THM-derived components, has also been proposed here for PAH. This review discusses the current state of THM, their working mechanisms against PAH, and prospects of reverse pharmacology, which are expected to facilitate the natural anti-PAH medicine discovery and development and its bench-to-bedside transformation.

7.
Virol Sin ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34558014

RESUMO

Japanese encephalitis virus (JEV) is a leading cause of viral encephalitis in endemic regions of Asia. The neurotropism of JEV and its high-efficiency replication in neurons are the key events for pathogenesis. Revealing the interplay between virus and host cells in metabolic facet is of great importance both for unraveling the pathogenesis mechanisms and providing novel antiviral targets. This study took advantage of the integration analysis of metabolomics and transcriptomics to depict the metabolic profiles of neurons during the early stage of JEV infection. Increased glycolysis and its branched pentose phosphate pathway (PPP) flux and impaired oxidative phosphorylation (OXPHOS) in glucose utilization, and the catabolic patterns of lipid metabolism were created to facilitate the biosynthesis of precursors needed for JEV replication in neurons. Pharmacological inhibitions of both glycolysis pathway and PPP in neurons suggested its indispensable role in maintaining the optimal propagation of JEV. In addition, analysis of metabolomic-transcriptomic regulatory network showed the pivotal biological function of lipid metabolism during JEV infection. Several pro-inflammatory lipid metabolites were significantly up-regulated and might partially be responsible for the progression of encephalitis. These unique metabolic reprogramming features might give deeper insight into JEV infected neurons and provide promising antiviral approaches targeting metabolism.

8.
Phytother Res ; 35(10): 5883-5898, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34427348

RESUMO

Efficient therapy of idiopathic pulmonary fibrosis (IPF) is still a major challenge. The current studies with single-target drug therapy are the pessimistic approaches due to the complex characteristics of IPF. Here, a combination therapy of Tanshinone IIA and Puerarin for IPF was proposed to alleviate IPF due to their antiinflammatory and anti-fibrotic effects. In vivo, the combination therapy could significantly attenuate the area of ground glass opacification that was presented by 85% percentile density score of the micro-CT images when compared to single conditions. In addition, the combination therapy enormously improved the survival rate and alleviated pathological changes in bleomycin (BLM)-induced IPF mice. By using a wide spectrum of infiltration biomarkers in immunofluorescence assay in pathological sections, we demonstrate that fewer IL6 related macrophage infiltration and fibrosis area after this combination therapy, and further proved that IL6-JAK2-STAT3/STAT1 is the key mechanism of the combination therapy. In vitro, combination therapy markedly inhibited the fibroblasts activation and migration which was induced by TGF-ß1 or/and IL6 through JAK2-STAT3/STAT1 signaling pathway. This study demonstrated that combination therapeutic effect of TanIIA and Pue on IPF may be related to the reduced inflammatory response targeting IL6, which could be an optimistic and effective approach for IPF.


Assuntos
Interleucina-6 , Fibrose Pulmonar , Abietanos , Animais , Bleomicina , Fibroblastos/metabolismo , Interleucina-6/metabolismo , Isoflavonas , Pulmão/metabolismo , Camundongos , Fibrose Pulmonar/tratamento farmacológico , Fator de Transcrição STAT1 , Transdução de Sinais
9.
Biomed Pharmacother ; 141: 111941, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34328102

RESUMO

BACKGROUND: Hypertension is a leading risk factor for developing kidney disease. Current single-target antihypertensive drugs are not effective for hypertensive nephropathy, in part due to its less understood mechanism of pathogenesis. We recently showed that QiShenYiQi (QSYQ), a component-based cardiovascular Chinese medicine, is also effective for ischemic stroke. Given the important role of the brain-heart-kidney axis in blood pressure control, we hypothesized that QSYQ may contribute to blood pressure regulation and kidney protection in Dahl salt-sensitive hypertensive rats. METHODS: The therapeutic effects of QSYQ on blood pressure and kidney injury in Dahl salt-sensitive rats fed with high salt for 9 weeks were evaluated by tail-cuff blood pressure monitoring, renal histopathological examination and biochemical indicators in urine and serum. RNA-seq was conducted to identify QSYQ regulated genes in hypertensive kidney, and RT-qPCR, immunohistochemistry, and Western blotting analysis were performed to verify the transcriptomics results and validate the purposed mechanisms. RESULTS: QSYQ treatment significantly decreased blood pressure in Dahl salt-sensitive hypertensive rats, alleviated renal tissue damage, reduced renal interstitial fibrosis and collagen deposition, and improved renal physiological function. RNA-seq and subsequent bioinformatic analysis showed that the expression of ADRA1D and SIK1 genes were among the most prominently altered by QSYQ in salt-sensitive hypertensive rat kidney. RT-qPCR, immunohistochemistry and Western blotting results confirmed that the mRNA and protein expression levels of alpha-1D adrenergic receptor (ADRA1D) in the kidney tissue of the QSYQ-treated rats were markedly down-regulated, while the mRNA and protein levels of salt inducible kinase 1 (SIK1) were significantly increased. CONCLUSION: QSYQ not only lowered blood pressure, but also alleviated renal damage via reducing the expression of ADRA1D and increasing the expression of SIK1 in the kidney of Dahl salt-sensitive hypertensive rats.

10.
Front Immunol ; 12: 613907, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33679754

RESUMO

Idiopathic pulmonary fibrosis (IPF) is serious chronic lung disease with limited therapeutic approaches. Inflammation and immune disorders are considered as the main factors in the initiation and development of pulmonary fibrosis. Inspired by the key roles of macrophages during the processes of inflammation and immune disorders, here, we report a new method for direct drug delivery into the in-situ fibrotic tissue sites in vitro and in vivo. First, liposomes containing dexamethasone (Dex-L) are prepared and designed to entry into the macrophages in the early hours, forming the macrophages loaded Dex-L delivery system (Dex-L-MV). Chemokine and cytokine factors such as IL-6, IL-10, Arg-1 are measured to show the effect of Dex-L to the various subtypes of macrophages. Next, we mimic the inflammatory and anti-inflammatory microenvironment by co-culture of polarized/inactive macrophage and fibroblast cells to show the acute inflammation response of Dex-L-MV. Further, we confirm the targeted delivery of Dex-L-MV into the inflammatory sites in vivo, and surprisingly found that injected macrophage containing Dex can reduce the level of macrophage infiltration and expression of the markers of collagen deposition during the fibrotic stage, while causing little systematic toxicity. These data demonstrated the suitability and immune regulation effect of Dex-L-MV for the anti-pulmonary process. It is envisaged that these findings are a step forward toward endogenous immune targeting systems as a tool for clinical drug delivery.


Assuntos
Microambiente Celular/efeitos dos fármacos , Microambiente Celular/imunologia , Dexametasona/administração & dosagem , Imunossupressores/administração & dosagem , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/imunologia , Animais , Biomarcadores , Movimento Celular/efeitos dos fármacos , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/etiologia , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/patologia , Lipossomos , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos Alveolares/metabolismo , Camundongos , Células NIH 3T3 , Células RAW 264.7
11.
Mini Rev Med Chem ; 20(13): 1258-1271, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32386491

RESUMO

Pulmonary pharmaceutical formulations are targeted for the treatment of respiratory diseases. However, their application is limited due to the physiological characteristics of the lungs, such as branching structure, mucociliary and macrophages, as well as certain properties of the drugs like particle size and solubility. Nano-formulations can ameliorate particle sizes and improve drug solubility to enhance bioavailability in the lungs. The nano-formulations for lungs reviewed in this article can be classified into nanocarriers, no-carrier-added nanosuspensions and polymer-drug conjugates. Compared with conventional inhalation preparations, these novel pulmonary pharmaceutical formulations have their own advantages, such as increasing drug solubility for better absorption and less inflammatory reaction caused by the aggregation of insoluble drugs; prolonging pulmonary retention time and reducing drug clearance; improving the patient compliance by avoiding multiple repeated administrations. This review will provide the reader with some background information for pulmonary drug delivery and give an overview of the existing literature about nano-formulations for pulmonary application to explore nano-strategies for improving the bioavailability of pulmonary pharmaceutical formulations.


Assuntos
Portadores de Fármacos/química , Nanopartículas/química , Preparações Farmacêuticas/química , Administração por Inalação , Anti-Infecciosos/química , Anti-Infecciosos/farmacocinética , Anti-Infecciosos/uso terapêutico , Disponibilidade Biológica , Composição de Medicamentos , Humanos , Pneumopatias/tratamento farmacológico , Pneumopatias/patologia , Preparações Farmacêuticas/metabolismo , Polímeros/química
12.
J Aerosol Med Pulm Drug Deliv ; 33(2): 73-82, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31660760

RESUMO

Background: Salvia miltiorrhiza polyphenolic acid (SMPA) is effective in the treatment of cardiovascular diseases and currently it is administered orally or intravenously. However, SMPA is poorly absorbed orally and quickly eliminated in vivo. A long-term frequent intravenous administration leads to poor patient compliance. Therefore, it is urgently demanded to find a new alternative route of noninjection drug delivery system for SMPA. Methods: Two dry powder inhalation (DPI) formulations of spray-dried SMPA formulation (P1) and spray-dried SMPA-L-leucine formulation (P2) were prepared by spray drying method and their physicochemical properties were assessed by thermogravimetric analysis, X-ray diffraction, scanning electron microscopy, particle size distribution analysis, and in vitro aerodynamic analysis. Moreover, In vitro cytotoxicity of SMPA and P2 was conducted with NR8383 cells. In vivo pharmacokinetics were carried out by Penn-Century endotracheal intubation technique to deliver P2 to the lungs of rats. Results and Conclusions: The moisture content of P1 and P2 were 5.81% ± 0.005%, and 4.08% ± 0.002%, respectively. P1 and P2 were in an amorphous state. Moreover, P1 had slightly corrugated surfaces, whereas P2 exhibited severely corrugated surfaces with invagination due to the presence of L-leucine. In addition, there were more hollow particles with smooth surface in P1 than that in P2. Compared with P1, P2 has shown optimal physical particle size and aerosolization behavior with D (v, 50) of 2.64 ± 0.01 µm and fine particle fraction of 37.55% ± 2.63%. The findings of in vitro cytotoxicity showed that P2 did not inhibit cell viability and could be safe for pulmonary administration. The absolute bioavailability of salvianolic acid B (Sal B) for pulmonary administration was 19.15% ± 7.44%, which is significantly higher than the oral bioavailability of Sal B (<5.56%). In this study, we have shown the feasibleness of pulmonary administration of SMPA in the form of DPIs for systemic delivery to treat cardiovascular diseases.


Assuntos
Sistemas de Liberação de Medicamentos , Leucina/administração & dosagem , Polifenóis/administração & dosagem , Salvia miltiorrhiza/química , Administração por Inalação , Aerossóis , Animais , Disponibilidade Biológica , Linhagem Celular , Leucina/isolamento & purificação , Leucina/farmacocinética , Pulmão/metabolismo , Masculino , Tamanho da Partícula , Polifenóis/isolamento & purificação , Polifenóis/farmacologia , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
13.
Int J Pharm ; 571: 118754, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31604118

RESUMO

In order to deliver Salvianolic acid B (Sal B) and Baicalin (BA) to the brain tissue to repair neuron damage and improve cerebral ischemia-reperfusion injury (IRI), in our previous study, a nanostructured lipid carrier (NLC) containing BA and Sal B, and modified by the transferrin receptor monoclonal antibody OX26 (OX26-BA/Sal B-NLC) was constructed. The present study is to evaluate its in vitro release behavior, in vitro and in vivo targeting ability, in vitro pharmacodynamics and brain pharmacokinetics. The results showed that the release mechanism of the formulation was in line with the Weibull model release equation. The in-vitro and in-vivo targeting ability study exhibited that OX26 modified formulations was obviously higher than that of non-modified and solution groups. The results of in vitro preliminary study to investigate the protective effect of OX26-BA/Sal B-NLC on oxygen-glucose deprivation/reperfusion injured cells showed that it could decrease the injury. Furthermore, the results of brain microdialysis study showed that the OX26-modified preparation group could significantly increase the content of BA in the brain. In the solution group and the unmodified group, Sal B can only be detected at few time points, while OX26-modified BA/Sal B-NLC could be detected within 4 h. These results indicating that OX26-modified NLC can promote the brain delivery of Sal B and BA combination.


Assuntos
Anticorpos Monoclonais/química , Benzofuranos/administração & dosagem , Portadores de Fármacos/química , Medicamentos de Ervas Chinesas/administração & dosagem , Flavonoides/administração & dosagem , Traumatismo por Reperfusão/tratamento farmacológico , Administração Intravenosa , Animais , Anticorpos Monoclonais/farmacologia , Benzofuranos/farmacocinética , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Encéfalo/patologia , Linhagem Celular , Modelos Animais de Doenças , Portadores de Fármacos/farmacologia , Combinação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Liberação Controlada de Fármacos , Medicamentos de Ervas Chinesas/farmacocinética , Flavonoides/farmacocinética , Humanos , Lipídeos/química , Masculino , Camundongos , Microdiálise , Nanopartículas/química , Permeabilidade , Receptores da Transferrina/antagonistas & inibidores , Traumatismo por Reperfusão/patologia , Distribuição Tecidual
14.
Molecules ; 24(11)2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31141901

RESUMO

A UHPLC-QQQ-MS/MS method was developed to quantify the significant constituents in Wen-Dan Decoction (WDD), a traditional Chinese medicine. Analysis of 19 compounds was conducted on an ACQUITY UPLC® BEH C18 Column (2.1 × 50 mm, 1.7 µm) using elution with a gradient elution of acetonitrile and 0.05% (v/v) formic acid in water. A triple quadrupole mass spectrometer was operated in negative ionization mode and positive ionization mode by multiple reaction monitoring (MRM), respectively. All calibration curves showed acceptable linearity (r ≥ 0.9950). The RSDs of intra- and inter-day precisions of low, mid and high concentrations were ≤ 8.88%. The repeatabilities (RSDs ≤ 7.17%) and stabilities (RSD ≤ 4.79%) of the samples were qualified. The recoveries were found in the range of 93.07 ± 3.86 to 103.98 ± 2.98% with the RSD varying between 1.30 and 7.86%. The final rapid, sensitive, precise, accurate and reliable UHPLC-QQQ-MS/MS method was used for the simultaneous quantification of 19 constituents in WDD and its commercial preparations. The strategy of combining the contents of the 19 chemicals in a daily dose of the WDD preparations with the hierarchical cluster analysis and the 3D principal component analysis was employed to effectively distinguish the WDD preparations provided by the different suppliers, which represents a contribution to the evaluation and control of the quality of WDD (or other decoctions consisting of the same herbs) and the preparations of WDD in other dosage forms such as tablets and granules.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Medicina Tradicional Chinesa , Compostos Fitoquímicos/análise , Análise por Conglomerados , Limite de Detecção , Compostos Fitoquímicos/química , Padrões de Referência , Espectrometria de Massas em Tandem
15.
Biomed Chromatogr ; 33(8): e4561, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31017297

RESUMO

A sensitive and accurate LC-MS/MS method was established for quantifying salvianolic acid B (Sal B), rosmarinic acid (Ros A) and Danshensu (DA) in rat plasma. Salvia miltiorrhiza polyphenolic acid (SMPA), active water-soluble ingredients isolated and purified from Salvia miltiorrhiza Bge included Sal B, Ros A and DA. The pharmacokinetic analysis of Sal B, Ros A and DA after pulmonary administration of SMPA solution to rat was performed by LC-MS/MS. Results from the pharmacokinetic studies showed that the peak concentration of DA was 21.85 ± 6.43 and 65.39 ± 3.83 ng/mL after pulmonary and intravenous administration, respectively. DA was not detected at 2 h after administration. The absolute bioavailabilities of Sal B and Ros A were respectively 50.37 ± 27.04 and 89.63 ± 12.16% after pulmonary administration of 10 mg/kg SMPA solution in rats. The absolute bioavailability of Sal B increased at least 10-fold after pulmonary administration, compared with oral administration. It was concluded that the newly established LC-MS/MS method was suitable for describing the pharmacokinetic characteristics of Sal B, Ros A and DA in rat after pulmonary administration of SMPA solution. The data from this study will provide a preclinical insight into the feasibility of pulmonary administration of SMPA.


Assuntos
Benzofuranos/farmacocinética , Cinamatos/farmacocinética , Depsídeos/farmacocinética , Medicamentos de Ervas Chinesas/administração & dosagem , Lactatos/farmacocinética , Salvia miltiorrhiza , Administração por Inalação , Animais , Benzofuranos/sangue , Benzofuranos/química , Disponibilidade Biológica , Cromatografia Líquida , Cinamatos/sangue , Cinamatos/química , Depsídeos/sangue , Depsídeos/química , Estabilidade de Medicamentos , Lactatos/sangue , Lactatos/química , Limite de Detecção , Modelos Lineares , Masculino , Polifenóis , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos
16.
Int J Nanomedicine ; 14: 10179-10194, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32021160

RESUMO

Nanoparticle drug formulations have enormous application prospects owing to achievement of targeted and sustained release drug delivery, improvement in drug solubility and reduction of adverse drug reactions. Recently, a variety of efficient drug nanometer carriers have been developed, among which carbon nanotubes (CNT) have been increasingly utilized in the field of cancer therapy. However, these nanotubes exert various toxic effects on the body due to their unique physical and chemical properties. CNT-induced toxicity is related to surface modification, degree of aggregation in vivo, and nanoparticle concentration. This review has focused on the potential toxic effects of CNTs utilized as anti-tumor drug carriers. The main modes by which CNTs enter target sites, the toxicity expressive types and the factors affecting toxicity are discussed.


Assuntos
Antineoplásicos/administração & dosagem , Portadores de Fármacos/efeitos adversos , Nanotubos de Carbono/toxicidade , Animais , Portadores de Fármacos/química , Portadores de Fármacos/toxicidade , Humanos , Nanotubos de Carbono/efeitos adversos , Nanotubos de Carbono/química , Solubilidade
17.
Mol Med Rep ; 12(5): 7749-55, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26460178

RESUMO

Disease biomarkers for diagnostic and prognostic purposes are most likely within an extremely low concentration range and are thus masked by the presence of high­abundance proteins. Therefore, removing high­abundance proteins is the main challenge for identifying disease biomarkers. In addition, the solution obtained from high­abundance protein depletion kits contains a rich array of compounds, which interfere with isoelectric focusing (IEF). In the present study, the effect of two commercial kits was evaluated and the downstream IEF protocol was optimized. High­resolution results could be obtained according to the following conditions: The ProteoPrep Blue Albumin and IgG Depletion kit depleted albumin and IgG; immobilized pH gradient strips (typically 18 cm) were rehydrated with sample buffer containing 250 µg serum proteins at 30 v for 6 h, 60 v for 6 h, 200 v for 2 h, 500 v for 2 h, 1,000 v for 2 h, 5,000 v for 2 h, 10,000 v for 2 h and then focusing at 10,000 v up to 110 k vhs. In addition, the protein spots identified by matrix­assisted laser desorption ionization time­of­flight mass spectrometry demonstrated that all proteins had a low abundance. The present study not only provides a definite and effective method for removing high­abundance proteins, but also provides a proper protocol (protocol C) for downstream IEF. The present study includes a comprehensive investigation of serum proteomics, which paves the way for serum protein research.


Assuntos
Proteínas Sanguíneas/análise , Imunoglobulina G/isolamento & purificação , Focalização Isoelétrica/métodos , Proteômica/métodos , Albumina Sérica/isolamento & purificação , Adulto , Neoplasias do Colo/sangue , Eletroforese em Gel de Poliacrilamida/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
18.
Rheumatol Int ; 35(8): 1351-60, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26007152

RESUMO

Background Vascular endothelial growth factor (VEGF) is an important angiogenic factor and may be connected with chronic immune-mediated inflammatory diseases (IMIDs) to some extent. However, previous researches about the relationship between the +405G>C (dbSNP: rs2010963) polymorphism in VEGF gene and the risk of IMIDs are controversial and inconsistent. So we conducted this meta-analysis to assess whether the relationship between the +405G>C polymorphism in the 5'-UTR region of VEGF gene and IMID susceptibility exists. Methods Our literature search was conducted on the PubMed, Embase, Web of science, Chinese National Knowledge Infrastructure, and Chinese Biomedical databases to retrieve for eligible studies. Odds ratios as well as their 95 % confidence intervals were utilized to deduce the possible relationship. Results A total number of 5175 patients with IMIDs and 7069 healthy controls from 27 case-control studies were included. For the overall eligible data collected in our meta-analysis, there was no marked relationship between +405G>C polymorphism and the risk of IMIDs. However, subgroup analysis by ethnicity suggested that +405C allele could be a protective factor for IMIDs in Asians, whereas an opposite conclusion was drawn in Caucasians. Conclusion Thus, we may come to the conclusion that the VEGF +405G>C polymorphism could be associated with IMIDs, and the correlation might vary with ethnic groups.


Assuntos
Doenças Autoimunes/genética , Fator A de Crescimento do Endotélio Vascular/genética , Alelos , Artrite Reumatoide/genética , Síndrome de Behçet/genética , Diabetes Mellitus Tipo 1/genética , Predisposição Genética para Doença , Arterite de Células Gigantes/genética , Doença de Graves/genética , Humanos , Lúpus Eritematoso Sistêmico/genética , Síndrome de Linfonodos Mucocutâneos/genética , Razão de Chances , Polimorfismo de Nucleotídeo Único , Psoríase/genética , Escleroderma Sistêmico/genética , /genética
19.
Phys Chem Chem Phys ; 16(21): 9849-58, 2014 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-24398903

RESUMO

Cold water oligomers (H2O)n and (D2O)n with n = 2-5 are assigned in spontaneous Raman scattering spectra of seeded rare gas expansions for the first time. Comparison with infrared spectra provides direct experimental insights into the hydrogen bond-mediated excitonic OH oscillator coupling, which is responsible for ultrafast energy transfer between water molecules, usually suppressed by isotopic dilution in femtosecond experiments for the condensed phase. The experimental coupling constants are compared to those in state-of-the-art full-dimensional water potential energy hypersurfaces, leaving room for improvement in the description of the coupled dynamics in water. Evidence for intensified Fermi resonance between OH stretching and OH bending motion beyond water trimers is collected.

20.
J Am Chem Soc ; 133(50): 20194-207, 2011 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-21961479

RESUMO

Aggregation in hydroxyacetone (HA) is studied using low-temperature FTIR, supersonic jet expansion, and X-ray crystallographic (in situ cryocrystallization) techniques. Along with quantum chemical methods (MP2 and DFT), the experiments unravel the conformational preferences of HA upon aggregation to dimers and oligomers. The O-H···O═C intramolecular hydrogen bond present in the gas-phase monomer partially opens upon aggregation in supersonic expansions, giving rise to intermolecular cooperatively enhanced O-H···O-H hydrogen bonds in competition with isolated O-H···O═C hydrogen bonds. On the other hand, low-temperature IR studies on the neat solid and X-ray crystallographic data reveal that HA undergoes profound conformational changes upon crystallization, with the HOCC dihedral angle changing from ~0° in the gas phase to ~180° in the crystalline phase, hence giving rise to a completely new conformation. These conclusions are supported by theoretical calculations performed on the geometry derived from the crystalline phase.

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