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1.
Nat Commun ; 12(1): 822, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33547288

RESUMO

Optimising the balance between propene selectivity, propene/ethene ratio and catalytic stability and unravelling the explicit mechanism on formation of the first carbon-carbon bond are challenging goals of great importance in state-of-the-art methanol-to-olefin (MTO) research. We report a strategy to finely control the nature of active sites within the pores of commercial MFI-zeolites by incorporating tantalum(V) and aluminium(III) centres into the framework. The resultant TaAlS-1 zeolite exhibits simultaneously remarkable propene selectivity (51%), propene/ethene ratio (8.3) and catalytic stability (>50 h) at full methanol conversion. In situ synchrotron X-ray powder diffraction, X-ray absorption spectroscopy and inelastic neutron scattering coupled with DFT calculations reveal that the first carbon-carbon bond is formed between an activated methanol molecule and a trimethyloxonium intermediate. The unprecedented cooperativity between tantalum(V) and Brønsted acid sites creates an optimal microenvironment for efficient conversion of methanol and thus greatly promotes the application of zeolites in the sustainable manufacturing of light olefins.

2.
J Am Chem Soc ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33606937

RESUMO

Ammonia (NH3) is a promising energy resource owing to its high hydrogen density. However, its widespread application is restricted by the lack of efficient and corrosion-resistant storage materials. Here, we report high NH3 adsorption in a series of robust metal-organic framework (MOF) materials, MFM-300(M) (M = Fe, V, Cr, In). MFM-300(M) (M = Fe, VIII, Cr) show fully reversible capacity for >20 cycles, reaching capacities of 16.1, 15.6, and 14.0 mmol g-1, respectively, at 273 K and 1 bar. Under the same conditions, MFM-300(VIV) exhibits the highest uptake among this series of MOFs of 17.3 mmol g-1. In situ neutron powder diffraction, single-crystal X-ray diffraction, and electron paramagnetic resonance spectroscopy confirm that the redox-active V center enables host-guest charge transfer, with VIV being reduced to VIII and NH3 being oxidized to hydrazine (N2H4). A combination of in situ inelastic neutron scattering and DFT modeling has revealed the binding dynamics of adsorbed NH3 within these MOFs to afford a comprehensive insight into the application of MOF materials to the adsorption and conversion of NH3.

3.
Int J Nanomedicine ; 15: 10385-10399, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33376327

RESUMO

Gambogic acid (GA), a kind of dry resin secreted by the Garcinia hanburyi tree, is a natural active ingredient with various biological activities, such as anti-cancer, anti-inflammatory, antioxidant, anti-bacterial effects, etc. An increasing amount of evidence indicates that GA has obvious anti-cancer effects via various molecular mechanisms, including the induction of apoptosis, autophagy, cell cycle arrest and the inhibition of invasion, metastasis, angiogenesis. In order to improve the efficacy in cancer treatment, nanometer drug delivery systems have been employed to load GA and form micelles, nanoparticles, nanofibers, and so on. In this review, we aim to offer a summary of chemical structure and properties, anti-cancer activities, drug delivery systems and combination therapy of GA, which might provide a reference to promote the development and clinical application of GA.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Xantonas/administração & dosagem , Xantonas/farmacologia , Antineoplásicos Fitogênicos/administração & dosagem , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Garcinia/química , Humanos , Micelas , Nanoestruturas , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neovascularização Patológica/tratamento farmacológico , Xantonas/química
4.
Liver Cancer ; 9(5): 563-582, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33083281

RESUMO

Background: Liver cancer is one of the leading causes of cancer-related deaths worldwide. The primary causes of liver cancer include hepatitis B virus (HBV), hepatitis C virus (HCV), alcohol consumption, nonalcoholic fatty liver disease, and other factors. Aims: The objective of this study was to evaluate the global and sex-, age-, region-, country-, and etiology-related liver cancer burden, as well as the trends in liver cancer caused by different etiologies. Methods: The causes of liver cancer from 1990 to 2017, including global, regional, and national liver cancer incidence, mortality, and etiology, were collected from the Global Burden of Disease study 2017, and the time-dependent change in the trends of liver cancer burden was evaluated by annual percentage change. Results: The global liver cancer incidence and mortality have been increasing. There were 950,000 newly-diagnosed liver cancer cases and over 800,000 deaths in 2017, which is more than twice the numbers recorded in 1990. HBV and HCV are the major causes of liver cancer. HBV is the major risk factor of liver cancer in Asia, while HCV and alcohol abuse are the major risk factors in the high sociodemographic index and high human development index regions. The mean onset age and incidence of liver cancer with different etiologies have gradually increased in the past 30 years. Conclusions: The global incidence is still rising and the causes have national, regional, or population specificities. More targeted prevention strategies must be developed for the different etiologic types in order to reduce liver cancer burden.

5.
Drug Discov Today ; 25(12): 2080-2088, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33017690

RESUMO

The research and development (R&D) of new drugs indicates scientific progress and economic development. However, little is known regarding ongoing or recent clinical trials in China. We analyzed data from clinical trials published before December 31, 2019, and found that the annual registration numbers are increasing annually in the country. Based on clinical indications, most tested drugs target cancers, nervous system, infections, and the cardiovascular system. Furthermore, clinical trials are mostly concentrated in Beijing, Shanghai, and Jiangsu, and conducted by large pharmaceutical companies, with multiple trials for several generic drugs. Going forward, it will be necessary to promote R&D in China of clinically relevant innovative drugs, drug delivery systems, and novel traditional Chinese medicine (TCM) and biological products, as well as to have a balanced distribution of clinical trials to sustainably meet public health needs.

6.
J Am Chem Soc ; 142(36): 15235-15239, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32786806

RESUMO

Nitrogen dioxide (NO2) is a toxic air pollutant, and efficient abatement technologies are important to mitigate the many associated health and environmental problems. Here, we report the reactive adsorption of NO2 in a redox-active metal-organic framework (MOF), MFM-300(V). Adsorption of NO2 induces the oxidation of V(III) to V(IV) centers in MFM-300(V), and this is accompanied by the reduction of adsorbed NO2 to NO and the release of water via deprotonation of the framework hydroxyl groups, as confirmed by synchrotron X-ray diffraction and various experimental techniques. The efficient packing of {NO2·N2O4}∞ chains in the pores of MFM-300(VIV) results in a high isothermal NO2 uptake of 13.0 mmol g-1 at 298 K and 1.0 bar and is retained for multiple adsorption-desorption cycles. This work will inspire the design of redox-active sorbents that exhibit reductive adsorption of NO2 for the elimination of air pollutants.

7.
Int J Nanomedicine ; 15: 3251-3266, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32440122

RESUMO

Background: Peripheral neuropathy is a common and painful side effect that occurs in patients with cancer induced by Oxaliplatin (OXL). The neurotoxicity correlates with the damage of dorsal root ganglion (DRG) neurons and Schwann cells (SCs). Hydroxysafflor yellow A (HSYA), icariin, epimedin B and 3, 4-dihydroxybenzoic acid (DA) are the main neuroprotective ingredients identified in Wen-Luo-Tong (WLT), a traditional Chinese medicinal topical compound. The purpose of this study was to prepare and evaluate the efficacy of an ethosomes gel formulation loaded with a combination of HSYA, icariin, epimedin B and DA. However, the low LogP value, poor solubility and macromolecule are several challenges for topical delivery of these drugs. Methods: Ethosomes were prepared by the single-step injection technique. Particle size, entrapment efficiency and in vitro drug deposition studies were determined to select the optimum ethosomes. The optimized ethosomes were further incorporated into carbopol to obtain a gel. The rheological properties, morphology, in vitro drug release, in vitro gel application and skin distribution of the ethosomes gels were studied. A rat model of oxaliplatin-induced neuropathy was established to assess the therapeutic efficacy of the ethosomes gel. Results: Seventy percent (v/v) ethanol, cinnamaldehyde and Phospholipon 90G were employed to develop ethosomes a carrier system. This system had a high entrapment efficiency, carried large amounts of HSYA, epimedin B, DA and icarrin, and penetrated deep into the epidermis and dermis. The optimized ethosomes had the maximum deposition of icariin, HSYA, epimedin B and relative higher amount of DA in epidermis (2.00±0.13 µg/cm2, 5.72±0.75 µg/cm2, 1.97±0.27 µg/cm2 and 9.25±1.21 µg/cm2, respectively). 0.5% carbopol 980 was selected to develop the ethosomes gel with desirable viscoelasticity and spreadability, which was suitable for topical application. The mechanical allodynia and hyperalgesia induced by OXL in rats were significantly reduced after the new ethosomes gel was applied to rats compared to model group. Conclusion: Based on our findings, the ethosomes gel delivery system provided a new formulation for the topical delivery of HSYA, icariin, epimedin B and DA to counteract OXL-induced peripheral neuropathy.


Assuntos
Géis/química , Fármacos Neuroprotetores/uso terapêutico , Oxaliplatina/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Acroleína/análogos & derivados , Acroleína/química , Administração Tópica , Animais , Comportamento Animal , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Gânglios Espinais/citologia , Lipossomos , Masculino , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/farmacologia , Oxaliplatina/administração & dosagem , Tamanho da Partícula , Ratos Wistar , Reologia , Pele/metabolismo , Absorção Cutânea/efeitos dos fármacos
8.
Biomed Pharmacother ; 127: 110051, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32428832

RESUMO

Xiaosheng prescription (XSP) has been used for dry eye disease (DED) for more than 10 years in Eye Hospital of China Academy of Chinese Medicine Sciences. However, the effective ingredients involved have remained unclear, which was investigated in this study by the correlation of ingredient and therapeutic activity. Human corneal epithelial cells (HCEC) cultured with 110 mM NaCl solution in vitro and C57BL/6 mice injected subcutaneously with scopolamine hydrobromide were used to establish dry eye models, and the therapeutic effect of XSP extract 1 was better than that of XSP extract 2 significantly. Then, UPLC-Q-TOF/MS and data analysis program Progenesis QI and Makerlynx XS were used to analyze the potential effective ingredients of XSP, and 4 compounds were speculated and identified, in which Schisandrin and 1 µM of Schisantherin A could obviously increase the cell survival rate of injured cells on the cell model. It can be indicated that Schisandrin and Schisantherin A are probably the potential effective ingredients in XSP for DED.

9.
Int J Pharm ; 581: 119278, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32229284

RESUMO

Berberine chloride (BBR) and evodiamine (EVO) are two main active ingredients of "ZuoJinWan", a classical Chinese herbal medicine, and these compounds are known to have a synergistic inhibitory effect on various cancer cell lines. Several recent studies have reported anti-melanoma effects for both BBR and EVO. However, topical delivery of the two compounds has been challenging, due to their poor aqueous solubility and their low skin penetration. In the current study, we have combined BBR and EVO into an ethosomes delivery system with the future aim to design a novel topical anti-melanoma formulation. The ethosomes formulations were characterized using particle size, entrapment efficiency and an in vitro skin drug deposition study. The ethosome formulation displaying maximum drug deposition in the epidermis was selected for further study. This formulation contained ethosomes with mean size of 171 nm and 90% or above entrapment efficiency for both BBR and EVO. Cell viability tests proved the optimized ethosomes increased the inhibitory effect on B16 melanoma cells. These results corroborate that ethosomes containing a combination of BBR and EVO are a promising delivery system for potential use in melanoma therapy.

10.
Zhongguo Zhong Yao Za Zhi ; 45(3): 539-547, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32237511

RESUMO

To evaluate the traits and rheological properties of thermosensitive in situ gel of Yihuang Decoction and its common gel for vaginal use, and predict the release behavior of Yihuang Decoction in situ gel in vitro. Poloxamer was used as thermosensitive material to prepare Yihuang Decoction vaginal in situ gel, and Yihuang Decoction common gel was prepared with carbopol. Then the differences of the two gels before and after diluting with vaginal fluid were compared. The rheological parameters of Yihuang Decoction in situ gel and its common gel were determined with Anton Paar MCR102 rheometer. In addition, berberine hydrochloride was selected as an index component to evaluate the in vitro release properties of Yihuang Decoction vaginal thermosensitive in situ gel. Yihuang Decoction vaginal thermosensitive in situ gel was Newtonian fluid under low-temperature conditions, which was yellow and transparent. After reaching the gelling temperature of 24.5 ℃, it became semi-solid, pseudoplastic fluid. The gelling temperature was predicted to be 37 ℃, and the phase transition time was 30 s after diluting with simulated vaginal fluid. However, the rheological properties of Yihuang Decoction common gel had no significant changes with temperature. Compared with in situ gel, the color of common gel was darker and more translucent. Besides, its mobility was stronger after diluting with simulated vaginal fluid. The in vitro release study showed that the kinetic behavior of berberine hydrochloride in Yihuang Decoction vaginal thermosensitive in situ gel was matched with the Higuchi equation. Through simulation of vaginal administration, physical properties and dynamic rheological parameters were used to intuitively and scientifically evaluate the two gels. Compared with the common gel, the thermosensitive in situ gel could quickly attached to the vaginal mucosa and release drug, and thus was more suitable for developing vaginal administration of Yihuang Decoction, which also provides references for studying new vaginal preparation of Yihuang Decoction.


Assuntos
Administração Intravaginal , Medicamentos de Ervas Chinesas/química , Géis/química , Feminino , Humanos , Poloxâmero , Reologia , Temperatura , Viscosidade
11.
Nat Mater ; 19(1): 86-93, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31844281

RESUMO

The efficient production of light olefins from renewable biomass is a vital and challenging target to achieve future sustainable chemical processes. Here we report a hetero-atomic MFI-type zeolite (NbAlS-1), over which aqueous solutions of γ-valerolactone (GVL), obtained from biomass-derived carbohydrates, can be quantitatively converted into butenes with a yield of >99% at ambient pressure under continuous flow conditions. NbAlS-1 incorporates simultaneously niobium(V) and aluminium(III) centres into the framework and thus has a desirable distribution of Lewis and Brønsted acid sites with optimal strength. Synchrotron X-ray diffraction and absorption spectroscopy show that there is cooperativity between Nb(V) and the Brønsted acid sites on the confined adsorption of GVL, whereas the catalytic mechanism for the conversion of the confined GVL into butenes is revealed by in situ inelastic neutron scattering, coupled with modelling. This study offers a prospect for the sustainable production of butene as a platform chemical for the manufacture of renewable materials.


Assuntos
Alcenos/química , Lactonas/química , Zeolitas/química , Adsorção , Biomassa , Carboidratos/química , Catálise , Ligação de Hidrogênio , Teste de Materiais , Nêutrons , Espalhamento de Radiação , Espectroscopia de Infravermelho com Transformada de Fourier , Síncrotrons
12.
Zhongguo Zhong Yao Za Zhi ; 45(23): 5753-5761, 2020 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-33496116

RESUMO

The aim of this paper was to explore the potential molecular mechanism of Banxia Xiexin Decoction in the treatment of colon cancer through pharmacology network and molecular docking methods. The chemical constituents and action targets of 7 herbs from Banxia Xiexin Decoction were collected by using TCMSP database,Chinese Pharmacopoeia and literatures consultation. GeneCards database was used to predict the potential targets of colon cancer. GO biological process analysis and KEGG pathway enrichment analysis of the disease and drug intersection targets were carried out through DAVID database. "Component-target-pathway" network and protein-protein interaction(PPI) network were construction by using Cytoscape and STRING database,and then the core components and targets of Banxia Xiexin Decoction in the treatment of colon cancer were selected according to the topological parameters. Finally, Autodock Vina was used to realize the molecular docking of core components and key targets. The prediction results showed that there were 190 active compounds and 324 corresponding targets for Banxia Xiexin Decoction,involving 74 potential targets for colon cancer. Cytoscape topology analysis revealed 11 key targets such as STAT3,TP53,AKT1,TNF,IL6 and SRC, as well as 10 core components such as quercetin,ß-sitosterol,baicalein,berberine,and 6-gingerol.In bioinformatics enrichment analysis, 679 GO terms and 106 KEGG pathways were obtained, mainly involving PI3 K-AKT signaling pathway,TNF signaling pathway and TP53 signaling pathway. The results of molecular docking showed that baicalein,berberine,licochalcone A and 6-gingerol had a high affinity with SRC,STAT3,TNF and IL6. The results suggested that Banxia Xiexin Decoction could play an anti-colon cancer effect by inhibiting cell proliferation, regulating cell cycle, inducing apoptosis and anti-inflammatory function. The study revealed the multi-components,multi-targets and multi-pathways molecular mechanism of Banxia Xiexin Decoction,which could provide scientific basis and research ideas for the clinical application of Banxia Xiexin Decoction and the treatment of colon cancer with compound Chinese medicines.


Assuntos
Neoplasias do Colo , Medicamentos de Ervas Chinesas , Humanos , Simulação de Acoplamento Molecular , Tecnologia
13.
Biomed Pharmacother ; 120: 109531, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31648163

RESUMO

To better understand the hepatotoxicity of anthraquinone glycosides, the hepatotoxicity of six anthraquinone glycosides was evaluated. The results show that chrysophanol-8-O-glucoside(C8G) has strong hepatotoxicity and can lead to increased LDH leakage and ROS, decreased GSH and MMP in L-02 hepatocytes. The results of C8G hepatotoxicity proteomics shows that, a total of 773 differentially expressed proteins were screened and analyzed using GO analysis and Pathway enrichment analysis. Our results show that C8G can lead to abnormal oxidative phosphorylation by inhibiting the function of mitochondrial complexes, resulting in decreased mitochondrial membrane potential (MMP), increased reactive oxygen species (ROS), and eventually resulting in mitochondrial damage and apoptosis. Western blot results verified the accuracy of quantitative proteomic results, and also evaluated the expression of Bax, caspase-3, -8, -9, Bcl-2, Cyt C in the mitochondria and cytosolic. The mitochondrial respiratory chain complexes activity assay result also confirmed that C8G could inhibit the activity of all mitochondrial complexes. The results of this study indicate that the hepatotoxicity mechanism of C8G is related to mitochondrial dysfunction, especially the mitochondrial complex function.


Assuntos
Antraquinonas/toxicidade , Glucosídeos/toxicidade , Fígado/patologia , Antraquinonas/química , Linhagem Celular , Transporte de Elétrons/efeitos dos fármacos , Ontologia Genética , Glucosídeos/química , Humanos , L-Lactato Desidrogenase/metabolismo , Fígado/efeitos dos fármacos , Metaloproteinases da Matriz/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo
14.
J Hematol Oncol ; 12(1): 96, 2019 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-31511035

RESUMO

BACKGROUND AND AIMS: Cancer has become the second most serious disease threatening human health, followed by cardiovascular diseases. This study aimed to quantitatively estimate the mortality, morbidity, and analyze the trends of 29 cancer groups in 195 countries/regions between 1990 and 2017. METHODS: Detailed information of 29 cancer groups were collected from the Global Burden of Disease (GBD) study in 2017 and age-standardized incidence rates (ASIR) and age-standardized death rates (ASDR) of 29 cancer groups were calculated based on gender, age, region, and country. Trend analyses were conducted for major cancer types. RESULTS: In 2017, the global death population caused by cancer reached 9 million, which was nearly twice the number in 1990. The ASDR and ASIR of cancer in males were about 1.5 times those of females. Breast cancer showed the highest mortality rate in females in 2017. Individuals aged over 50 are at high risk of developing cancer and the number of cases and deaths in this age group accounted for more than 80% of all cancers in all age groups. Asia has the heaviest cancer burden due to its large population density. Different cancers in varied countries globally have their own characteristics. The ASDR and ASIR of some major cancers demonstrated changes from 1990 to 2017. CONCLUSIONS: Analyses of these data provided basis for future investigations to the common etiological factors, leading to the occurrence of different cancers, the development of prevention strategies based on local characteristics, socioeconomic and other conditions, and the formulation of more targeted interventions.


Assuntos
Carga Global da Doença/tendências , Neoplasias/epidemiologia , Neoplasias/mortalidade , Adolescente , Adulto , Idoso , Envelhecimento , Criança , Pré-Escolar , Feminino , Saúde Global , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/classificação , Fatores de Tempo , Adulto Jovem
15.
Cells ; 8(3)2019 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-30897821

RESUMO

Emodin is the main component of traditional Chinese medicines including rhubarb, Polygonum multiflorum, and Polygonum cuspidatum. It has confirmed hepatotoxicity and may be the main causative agent of liver damage associated with the above-mentioned traditional Chinese medicines. However, current research does not explain the mechanism of emodin in hepatotoxicity. In this study, L02 cells were used as a model to study the mechanism of emodin-induced hepatocyte apoptosis using quantitative proteomics, and the results were verified by Western blot. A total of 662 differentially expressed proteins were discovered and analyzed using Gene Ontology (GO) and pathway enrichment analysis. The results show that the oxidative phosphorylation pathway is highly represented. Abnormalities in this pathway result in impaired mitochondrial function and represent mitochondrial damage. This result is consistent with mitochondria membrane potential measurements. Analysis of differentially expressed proteins revealed that emodin mainly affects oxidative phosphorylation pathways by inhibiting the function of the mitochondrial respiratory chain complexes; the mitochondrial respiratory chain complex activity assay result also confirmed that emodin could inhibit the activity of all mitochondrial complexes. This results in an increase in caspase-3, a decrease in mitochondrial membrane potential (MMP,) an increase in reactive oxygen species (ROS), and disorders in ATP synthesis, etc., eventually leading to mitochondrial damage and hepatocyte apoptosis in vitro.


Assuntos
Emodina/toxicidade , Fígado/metabolismo , Fígado/patologia , Mitocôndrias/metabolismo , Proteômica/métodos , Apoptose/efeitos dos fármacos , Contagem de Células , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Transporte de Elétrons/efeitos dos fármacos , Ontologia Genética , Humanos , Fígado/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Modelos Biológicos , Fosforilação Oxidativa/efeitos dos fármacos , Proteoma/metabolismo , Transdução de Sinais/efeitos dos fármacos
16.
Pak J Pharm Sci ; 31(6): 2329-2332, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30473500

RESUMO

Isopropylidene shikimic acid (ISA), a new drug derviatived from Shikimic Acid, had been proved to be effective in the cerebral protection after cerebral ischemia and reperfusion. But there was little research on the physical pharmacy and biopharmaceutical properties about the drug. In order to provide some useful data for the pharmaceutical development of ISA, the solubility, stability and Oil/Water partition coefficient (LogP) were determined by the classic preformulation study method, and the transmembrane performance of ISA was studied by Franz -diffusion cell method in vitro. The results showed that ISA was water-soluble with a solubility 32.52mg/ml, which could be improved to 44.32 mg/ml by 1% (w/v) sodium dodecylsulfate; the LogP was -0.63; ISA was less stable in water but it was stable when pH greater than 6.0 and unstable when pH less than 6.0; the accumulated permeation rates at 1h were about 50% and more than 80% at 6h. Data obtained by the study indicated that the medium selection and pH control were important for liquid preparation of ISA, and avoiding dissolution and absorption in stomach was critical for the oral solid dosage forms. Mucosal drug delivery systems would be considered, according to the certain hydrophilic-lipophilic characters and good transmembrane capability.


Assuntos
Fármacos Neuroprotetores/química , Ácido Chiquímico/química , Composição de Medicamentos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Excipientes/química , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Fármacos Neuroprotetores/farmacologia , Permeabilidade , Ácido Chiquímico/análogos & derivados , Ácido Chiquímico/farmacologia , Dodecilsulfato de Sódio/química , Solubilidade , Solventes/química , Água/química
17.
Artigo em Inglês | MEDLINE | ID: mdl-30258467

RESUMO

Realgar and indigo naturalis are clinically combined to treat varieties of leukemia. Exploring the drug-drug interactions might be beneficial to find active substances and develop new targeted drugs. This study aimed at exploring the change of arsenic concentration in mice and across MDCK-MDR1 cells and the cytotoxicity on K562 cells when realgar and indigo naturalis were combined. In the presence or absence of indigo naturalis, pharmacokinetics and cell-based permeability assays were used to evaluate the change of arsenic concentration, and K562 cell line was applied to evaluate the change of cytotoxicity. The drug concentration-time profiles exhibited that the combination medication group generated higher AUC, thalf, and longer MRT for arsenic, compared with the single administration of realgar. The apparent permeability coefficients (Papp) of bidirectional transport in MDCK-MDR1 cell permeability experiments showed that arsenic permeability obviously went up when indigo naturalis was incubated together. The combination medication significantly decreased the cell viability of K562 cells when both the concentration of realgar and the concentration of indigo naturalis were nontoxic. The pharmacokinetic research, the MDCK-MDR1 based permeability study, and the K562 cytotoxicity study were united together to verify the combination medication of realgar and indigo naturalis enhanced the absorption and the permeability across cells for arsenic and effectively inhibited the proliferation of K562 cell line. The molecular binding of As4S4 and indirubin was analyzed by computational study. It is predicted that the formation of the complex [As4S4 …Indirubin] involves noncovalent interaction that changes the concentration of arsenic.

18.
Front Pharmacol ; 9: 505, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29887801

RESUMO

The liver injury induced by Polygonum multiflorum (PM) used for clinical treatment has recently received widespread attention. This study aimed to determine the hepatotoxicity of PM through pharmacokinetics studies. The extract of PM was separated to isolate the anthraquinone fraction, the tannin and polysaccharide fraction, the hydroxystilbene fraction, and the combined anthraquinone fraction. A rapid LC-MS/MS method was developed and validated to simultaneously analyze 2,3,5,4'-tetrahydroxystilbene-2-O-ß-glucoside (TSG), emodin-8-O-ß-D-glucopyranoside (EDG), and emodin in rat plasma, and was applied to the pharmacokinetics (PK) studies. The hepatotoxicity of different extracted parts of PM was evaluated through the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBil), direct bilirubin (DBil), and indirect bilirubin (IBil) in rat serum. The results showed that liver injury occurred in all the treated groups and that the hepatotoxicity performance of the total extract was different from other groups. The pharmacokinetic studies showed that the Cmax, Tmax, AUC, t1/2, and MRT of the major compounds of different extracted parts were significantly different in rat plasma at same dosage. Emodin-O-hex-sulfate, tetrahydroxystilbene-O-(galloyl)-hex, emodin (original and generated through EDG deglycosylation), and other free anthraquinones might be responsible for the hepatotoxicity of PM in vivo. PM extracts produced inhibitory effects on drug metabolic enzymes, include CYP3A4, CYP2C19, CYP2E1, UGT1A1, etc. And these effects may be related to its hepatotoxicity and pharmacokinetic behavior different. This information on hepatotoxicity and the pharmacokinetic comparison may be useful to understand the toxicological effects of PM.

19.
Artif Cells Nanomed Biotechnol ; 46(8): 1981-1991, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29130769

RESUMO

Chemotherapy induced neuropathy causes excruciating pain to cancer patients. Wen-Luo-Tong (WLT), a traditional Chinese medicinal compound, has been used to alleviate anti-cancer drug such as oxaliplatin-induced neuropathic pain for many years. However, the current route of administration of WLT is inconvenient and the active ingredients and mechanism of action of WLT are still unclear. To address these issues, we developed a novel formulation of WLT (W/O microemulsion) for the ease of application. New ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) methods were employed for analysis of the ingredients. We identified seven ingredients that penetrated through the skin into the Franz cell receptor solution and four of those ingredients were retained in skin tissue when WLT microemulsion was applied. We tested the microemulsion formulation on an oxaliplatin-induced neuropathy rat model and showed that this formulation significantly decreased oxaliplatin-induced mechanical hyperalgesia responses. Schwann cells (SCs) viability experiment in vitro was studied to test the protective effect of the identified seven ingredients. The result showed that Hydroxysafflor Yellow A, icariin, epimedin B and 4-dihydroxybenzoic acid significantly increased the viability of SCs after injured by Oxaliplatin. Our report presents the first novel formulation of WLT with neuroprotective effect and ease of use, which has potential for clinical applications.


Assuntos
Medicamentos de Ervas Chinesas , Fármacos Neuroprotetores , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Absorção Cutânea/efeitos dos fármacos , Pele/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/farmacologia , Emulsões , Masculino , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacocinética , Fármacos Neuroprotetores/farmacologia , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/farmacologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/metabolismo , Doenças do Sistema Nervoso Periférico/patologia , Piridinas/efeitos adversos , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
20.
Zhongguo Zhong Yao Za Zhi ; 42(10): 1964-1970, 2017 May.
Artigo em Chinês | MEDLINE | ID: mdl-29090558

RESUMO

To establish HPLC-MS/MS method for simultaneous determination of daphnetin, daphnoretin, and daphneticin in rat plasma after oral and intravenous administration of Daphne giraldii extract, and then use them in the calculation of pharmacokinetic parameters. Six sprague-dawley rats received intragastric administration of D. giraldii extract (daphnetin, daphnoretin and daphneticin were 88.40, 3.24 and 4.28 mg•kg⁻¹, respectively). Their drug plasma concentration was determined by LC-MS/MS with schisandrin as an internal standard to draw plasma concentration-time curve. The pharmacokinetic parameters were calculated by Kinetica 4.4. The results showed that the linear range was 5-1 000 µg•L⁻¹ for daphnetin, daphnoretin and daphneticin, and the method ological test showed conformance to the requirements.The intraday and inter-day variable coefficients (RSD) were both less than 15.0%, indicating that both of legitimate precise and accuracy were consistent with the analysis requirements of biological samples. For daphnetin, the pharmacokinetic parameters Tmax, Cmax, AUC0-t, T1/2 and MRT were 4 h, 858.96 µg•L⁻¹, 10 566.4 µg•L⁻¹â€¢h, 5.19 h and 9.43 h, respectively. For daphnoretin, the pharmacokinetic parameters Tmax, Cmax, AUC0-t, T1/2 and MRT were 2.92 h, 178.00 µg•L⁻¹, 905.89 µg•L⁻¹â€¢h, 3.50 h and 6.95 h, respectively. For daphneticin, the pharmacokinetic parameters Tmax, Cmax, AUC0-t, T1/2 and MRT were 2 h, 36.67 µg•L⁻¹, 355.11 µg•L⁻¹â€¢h, 4.95 h and 8.27 h, respectively. The LC-MS/MS analysis method established in this study was proved to be so accurate and sensitive that it can be applied to the pharmacokinetic study of daphnetin, daphnoretin and daphneticin.


Assuntos
Cumarínicos/sangue , Daphne/química , Extratos Vegetais/farmacocinética , Umbeliferonas/sangue , Animais , Cromatografia Líquida , Cumarínicos/farmacocinética , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Umbeliferonas/farmacocinética
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