RESUMO
Photodynamic therapy (PDT) is a well-established treatment modality, typically conducted with single-wavelength irradiation, which may not always be optimal for varying tumor locations and sizes. To address this, photosensitizers with absorption wavelengths ranging from 550 to 760 nm are being explored. Herein, a series of 5,15-diaryltetrabenzoporphyrins (Ar2TBPs) were synthesized. All compounds displayed obvious absorption at 550-700 nm (especially at â¼668 nm), intense fluorescence, efficient generation of singlet oxygen and good photodynamic antitumor effects. Notably, compound I3 (5,15-bis[(4-carboxymethoxy)phenyl]tetrabenzoporphyrin) showed excellent cytotoxicity against Eca-109 cell line upon red light irradiation, with an IC50 value of 0.45 µM, and phototherapeutic index of 25.8. Flow cytometry revealed that I3 could induce distinct cell apoptosis. In vivo studies revealed that compound I3 selectively accumulated at tumor site and exhibited outstanding PDT effect with antitumor activity under single-time administration and light irradiation, and revealed more efficiency than the clinical photosensitizer Verteporfin. These findings underscore the considerable promise of I3 as a robust theranostic agent, offering capabilities in real-time fluorescence imaging and serving as a potent photosensitizer for personalized and precise photodynamic therapy of tumors.
RESUMO
The synthesis of ideal photosensitizers (PSs) is considered to be the most significant bottleneck in photodynamic therapy (PDT). To discover novel PSs with excellent photodynamic anti-tumor activities, a series of novel photosensitizers 5,15-diaryl-10,20-dibromoporphyrins (I1-6) were synthesized by a facile method. Compared with hematoporphyrin monomethyl ether (HMME) as the representative porphyrin-based photosensitizers, it is found that not only the longest absorption wavelength of all compounds was red-shifted to therapeutic window (660 nm) of photodynamic therapy, but also the singlet oxygen quantum yields were significantly increased. Furthermore, all compounds exhibited lower dark toxicity (except I2) and stronger phototoxicity (except I4) against Eca-109 tumor cells than HMME. Among them, I3 possessed the highest singlet oxygen quantum yield (ΦΔ = 0.205), the lower dark toxicity and the strongest phototoxicity (IC50 = 3.5 µM) in vitro. The findings indicated the compounds I3 had the potential to become anti-tumor agents for PDT.
Assuntos
Neoplasias , Fotoquimioterapia , Porfirinas , Humanos , Fármacos Fotossensibilizantes/química , Oxigênio Singlete/química , Porfirinas/química , Neoplasias/tratamento farmacológicoRESUMO
Three new diterpenoids with an unusual carbon skeleton, pedilanins A-C (1-3), and nine new jatrophane diterpenoids, pedilanins D-L (4-12), along with five known ones (13-17), were isolated from Pedilanthus tithymaloides. Compounds 1-3 characterize an unprecedented tricyclo[10.3.0.02,9]pentadecane skeleton. Compounds 4-8 are rare examples of the jatrophanes bearing a cyclic hemiketal substructure. Their structures were determined by an extensive analysis of HRESIMS, NMR, quantum-chemical calculation, DP4+ probability, and X-ray crystallographic data. In the bioassay, compounds 1-12 dramatically reversed multidrug resistance in cancer cells with the fold-reversals ranging from 17.9 to 396.8 at the noncytotoxic concentration of 10 µM. The mechanism results indicated that compounds 2 and 3 inhibited the P-glycoprotein (Pgp) transporter function, thus reversing the drug resistance.
Assuntos
Diterpenos , Euphorbia , Estrutura Molecular , Euphorbia/química , Resistência a Múltiplos Medicamentos , Compostos Radiofarmacêuticos/farmacologia , Diterpenos/farmacologia , Diterpenos/químicaRESUMO
A photosensitizer with high phototoxicity, suitable amphipathy and low dark toxicity could play a pivotal role in photodynamic therapy (PDT). In this study, a facile and versatile approach was adopted to synthesize a series of novel fluorinated hematoporphyrin ether derivatives (I1-I5 and II1-II4), and the photodynamic activities of these compounds were studied. Compared to hematoporphyrin monomethyl ether (HMME), all PSs showed preferable photodynamic activity against A549 lung tumor cells. The longest visible absorption wavelength of these compounds was approximately 622 nm. Among them, II3 revealed the highest singlet oxygen yield (0.0957 min-1), the strongest phototoxicity (IC50 = 1.24 µM), the lowest dark toxicity in vitro, and exhibited excellent anti-tumor effects in vivo. So compound II3 could act as new drug candidate for photodynamic therapy.
Assuntos
Antineoplásicos/uso terapêutico , Éteres/uso terapêutico , Hematoporfirinas/uso terapêutico , Hidrocarbonetos Fluorados/uso terapêutico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Células A549 , Animais , Antineoplásicos/síntese química , Antineoplásicos/efeitos da radiação , Teoria da Densidade Funcional , Éteres/síntese química , Éteres/efeitos da radiação , Feminino , Hematoporfirinas/síntese química , Hematoporfirinas/efeitos da radiação , Humanos , Hidrocarbonetos Fluorados/síntese química , Hidrocarbonetos Fluorados/efeitos da radiação , Luz , Camundongos Endogâmicos BALB C , Camundongos Nus , Modelos Químicos , Neoplasias/patologia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/efeitos da radiação , Oxigênio Singlete/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
We designed a photon-counting receiver system for long-distance underwater wireless laser communication at different code rate Reed-Solomon (RS) and low-density parity check (LDPC) codes. The symbol error rate (SER) performance of the LDPC and RS codes with different signal-to-noise ratios was analyzed. The effects of the background noise, pulse stretching, and frame synchronization were considered in our receiver system. A water tank experiment confirmed that the 1/2-code-rate RS (255,127) is an excellent coding strategy for communication distances in the range of 90-130 m in Jerlov II water. We constructed a communication link with a SER of 6.31 × 10-4 in a distance of 120-m distance in Jerlov II water for RS (255,127) with 256-pulse-position modulation (PPM) at bandwidth of 13.7 MHz. The maximum link loss was -136.8 dB at λ = 532 nm. The attenuation lengths Natt were 35.88, which were equal at link distances up to 249.2 m in clear ocean water (Jerlov IB water type). The photon counting receiver system can achieve a receiving performance of 3.32 bits/photon. To the best of our knowledge, this is the longest communication attenuation length ever reported under 1 mJ single pulse energy for a narrow field-of-view photon-counting receiver system.
RESUMO
Deficiency in petroleum resources and increasing environmental concerns have pushed a bio-based economy to be built, employing a highly reproducible, metal contaminant free, sustainable and green biomanufacturing method. Here, a chiral drug intermediate L-pipecolic acid has been synthesized from biomass-derived lysine. This artificial bioconversion system involves the coexpression of four functional genes, which encode L-lysine α-oxidase from Scomber japonicus, glucose dehydrogenase from Bacillus subtilis, Δ1-piperideine-2-carboxylase reductase from Pseudomonas putida, and lysine permease from Escherichia coli. Besides, a lysine degradation enzyme has been knocked out to strengthen the process in this microbe. The overexpression of LysP improved the L-pipecolic acid titer about 1.6-folds compared to the control. This engineered microbial factory showed the highest L-pipecolic acid production of 46.7 g/L reported to date and a higher productivity of 2.41 g/L h and a yield of 0.89 g/g. This biotechnological L-pipecolic acid production is a simple, economic, and green technology to replace the presently used chemical synthesis.
Assuntos
Biomassa , Química Farmacêutica/métodos , Escherichia coli/metabolismo , Microbiologia Industrial/métodos , Lisina/química , Engenharia Metabólica/métodos , Ácidos Pipecólicos/química , Aminoácido Oxirredutases/química , Bacillus subtilis/genética , Química Farmacêutica/economia , Escherichia coli/genética , Fermentação , Glucose 1-Desidrogenase/genética , Química Verde/economia , Química Verde/métodos , Microbiologia Industrial/economia , Engenharia Metabólica/economia , Plasmídeos/genética , Pseudomonas putida/genética , EstereoisomerismoRESUMO
Two engineered Escherichia coli strains, DQ101 (MG1655 fadD -)/pDQTES and DQ101 (MG1655 fadD -)/pDQTESZ were constructed to investigate the free fatty acid production using ionic liquid-based acid- or enzyme-catalyzed bamboo hydrolysate as carbon source in this study. The plasmid, pDQTES, carrying an acyl-ACP thioesterase 'TesA of E. coli in pTrc99A was constructed firstly, and then (3R)-hydroxyacyl-ACP dehydratase was ligated after the TesA to give the plasmid pDQTESZ. These two strains exhibited efficient fatty acid production when glucose was used as the sole carbon source, with a final concentration of 2.45 and 3.32 g/L, respectively. The free fatty acid production of the two strains on xylose is not as efficient as that on glucose, which was 2.32 and 2.96 g/L, respectively. For mixed sugars, DQ101 (MG1655 fadD -)-based strains utilized glucose and pentose sequentially under the carbon catabolite repression (CCR) regulation. The highest total FFAs concentration from the mixed sugar culture reached 2.81 g/L by DQ101 (MG1655 fadD -)/pDQTESZ. Furthermore, when ionic liquid-based enzyme-catalyzed bamboo hydrolysate was used as the carbon source, the strain DQ101 (MG1655 fadD -)/pDQTESZ could produce 1.23 g/L FFAs with a yield of 0.13 g/g, and while it just produced 0.65 g/L free fatty acid with the ionic liquid-based acid-catalyzed bamboo hydrolysate as the feedstock. The results suggested that enzymatic catalyzed bamboo hydrolysate with ionic liquid pretreatment could serve as an efficient feedstock for free fatty acid production.
Assuntos
Ácidos Graxos não Esterificados/biossíntese , Líquidos Iônicos/química , Poaceae/química , Carboidratos/química , Meios de Cultura/química , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Fermentação , Glucose/química , Engenharia Metabólica , Microrganismos Geneticamente Modificados , Plasmídeos/genética , Plasmídeos/metabolismo , Tioléster Hidrolases/genética , Tioléster Hidrolases/metabolismoAssuntos
Dermatite , Ácido gama-Linolênico , Humanos , Ácidos Linoleicos , Oenothera biennis , Óleos de PlantasRESUMO
In this study, a simple in-situ preparation method for coating on Mg-Zn alloy in a carbonic acid solution was investigated. The formation of a precursor carbonate layer on the alloy surface was observed. As the soaking time increased, the solution gradually turned alkaline, leading to the transformation of the precursor into a basic carbonate coating with a layered hydroxide structure. The corrosion potential (Ecorr) of the coated samples initially decreased and then increased with increasing the soaking time. After 2 h of soaking, the lowest corrosion potential observed was approximately -1.5105 V. At 12 h, the corrosion potential reached around -1.4645 V, which was comparable to that of the ZK61M magnesium alloy. After 48 h, the corrosion potential was measured to be approximately -1.3507 V.
RESUMO
In the pursuit of new potent photosensitizers (PSs) for photodynamic therapy (PDT) with better efficacy, a series of 5,15-diaryltetranaphtho [2,3]porphyrins (Ar2TNPs) with two or four carboxyalkoxy groups were designed, synthesized, and evaluated. These new compounds exhibited strong, broad and red-shifted UV-vis absorptions at 729 nm and other strong absorptions at 446, 475, 650, 659, 714 nm for tumors and other diseases of varying sizes and depths. They possess high molar extinction coefficients (0.95 × 105-1.48 × 105 M-1 cm-1), good singlet oxygen quantum yields and photodynamic antitumor effects towards Eca-109 cells in vitro. It is suggested that the extension of porphyrin with naphthalene into Ar2TNP results into remarkable improvement of photophysical characteristics, while the introduction of carboxyalkoxy groups on meso-phenyl can significantly improve the solubility and photodynamic effects in vitro and in vivo. Notably, compound II3 can localize primarily in lysosomes of Eca-109 cells and induce substantial cell apoptosis after PDT. It can also selectively accumulate in tumor tissues and be traced real-timely through in vivo fluorescence imaging with distinctive inhibition of tumor growth. Therefore, compound II3 deserves to be considered as a promising PDT drug candidate for individualized tumor real-time tracing and treatment.
Assuntos
Neoplasias , Fotoquimioterapia , Porfirinas , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Porfirinas/farmacologia , ApoptoseRESUMO
OBJECTIVE: To explore the expression of microRNA-3162-3p in different clinical stages of childhood primary immune thrombocytopenia (ITP) and its significance. METHODS: Ninety-six children with ITP were enrolled and divided into new diagnosis group (n=40), persistent group (n=30) and chronic group (n=26) according to the course of disease. 80 healthy children were selected as the control group. Peripheral blood mononuclear cells (PBMNC) of ITP children and healthy children were isolated and cultured, and the expression of microRNA-3162-3p in PBMNC of subjects was detected by real-time fluorescence quantitative PCR. The contents of IL-17, IL-23, IL-10 and TGF-ß in PBMNC of subjects were determined by ELISA. The correlation between microRNA-3162-3p and platelet count, IL-17, IL-23, IL-10 and TGF-ß was analyzed. RESULTS: Compared with the control group, the expression of microRNA-3162-3p and IL-10 in PBMNC and platelet count of ITP children were significantly decreasedï¼P < 0.05ï¼, while IL-17, IL-23 and TGF-ß were significantly increased (P < 0.05). With the prolongation of the disease course, the expressions of microRNA-3162-3p and IL-10 in PBMNC and platelet count were significantly decreasedï¼P < 0.05ï¼, while the expressions of IL-17, IL-23 and TGF-ß were significantly increased (P < 0.05). The expression of microRNA-3162-3p in PBMNC was positively correlated with platelet count and IL-10 (r =0.716, 0.667), and negatively correlated with IL-17, IL-23, and TGF-ß (r =-0.540, -0.641, -0.560). CONCLUSION: MicroRNA-3162-3p expression is significantly reduced in PBMNC of children with ITP, and is involved in the regulation of Th17/Treg imbalance, which can be used as a potential therapeutic target of ITP.
Assuntos
MicroRNAs , Púrpura Trombocitopênica Idiopática , Criança , Humanos , Púrpura Trombocitopênica Idiopática/genética , Interleucina-10 , Interleucina-17 , Leucócitos Mononucleares , Fator de Crescimento Transformador beta , Interleucina-23RESUMO
In quest for new photosensitizers (PSs) with remarkable antitumor photodynamic efficacy, a series of fifteen quaternary ammonium (QA) cations conjugated 5,15-diaryltetranaphtho[2,3]porphyrins (Ar2TNPs) was synthesized and evaluated in vitro and in vivo to understand how variations in the length of the alkoxy group and the kind of QA cations on meso-phenyl influence the photodynamic antitumor activity. All final compounds (I1-5, II1-5, and III1-5) exhibited robust absorption at 729 nm with significant bathochromic shift and high molar extinction coefficients (1.16 × 105-1.41 × 105 M-1 cm-1), as well as other absorptions at 445, 475, 651, and 714 nm for tumors and other diseases of diverse sizes and depths. Upon exposure to 474 nm light, they displayed intense fluorescence emission with fluorescence quantum yields ranging from 0.32 to 0.43. The ability to generate reactive oxygen species (ROS) was also quantified, attaining a maximum rate of up to 0.0961 s-1. The IC50 values of all the compounds regarding phototoxicity and dark toxicity were determined using KYSE-150 cells, and the phototoxicity indices were calculated. Among these compounds, III1 demonstrated the highest phototoxic index with minimal dark toxicity, and suppressed successfully the growth of esophageal carcinoma xenograft with favorable tolerance in vivo. Furthermore, the histological results showed III1-mediated PDT had a significant cytotoxic effect on the tumor. These outcomes underscore the potential of III1 as a highly effective antitumor photosensitizer drug in photodynamic therapy (PDT).
Assuntos
Compostos de Amônio , Fotoquimioterapia , Porfirinas , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Porfirinas/farmacologia , CátionsRESUMO
OBJECTIVE: To explore the effect of dichloromethane extraction phase of ethanol extract from stem of Patrinia scabiosaefolia Fisch.(DPSS) on proliferation and differentiation of K562 cells and its related mechanism. METHODS: MTT assay was used to detect the effects of DPSS at 0, 25, 50, 100 and 200 µg/ml on the proliferation of K562 cells at 24, 48 and 72 hours. Flow cytometry was used to analyze the changes of cell cycle and apoptosis at 24 and 48 hours. Wright-Giemsa staining was used to observe the morphological changes of K562 cells. The cell surface antigens CD33 and CD11b were detected by flow cytometry. RESULTS: The proliferation of K562 cells treated with different concentrations of DPSS was inhibited in a time-dose dependent manner (r=-0.96). Cell cycle analysis showed that with the increase of DPSS concentration, cells in G2/M phase increased (r=0.88), and cells were blocked in G2/M phase. Flow cytometry results showed that with the apoptosis rate of K562 cells was the highest when treated with 200 µg/ml DPSS for 48 h. Morphological observation showed that the K562 cell body increased, the amount of cytoplasm increased, the ratio of nucleus to cytoplasm decreased, and the nuclear chromatin was rough after DPSS treatment. Cell differentiation antigen, CD33 and CD11b, were positively expressed after treated with DPSS. CONCLUSION: DPSS can induce apoptosis through cell cycle arrest, inhibit the proliferation of K562 cells, and induce K562 cells to differentiate into monocytes, which has a potential anti-leukemia effect.
Assuntos
Patrinia , Humanos , Células K562 , Cloreto de Metileno/farmacologia , Apoptose , Proliferação de Células , Diferenciação CelularRESUMO
OBJECTIVE: To investigate the effect of phorbol-12-myristate-13-ace-tate (TPA) on the proliferation and apoptosis of acute promyelocytic leukemia cell line NB4 and its molecular mechanism. METHODS: The effect of different concentrations of TPA on the proliferation of NB4 cells at different time points was detected by CCK-8 assay. The morphological changes of NB4 cells were observed by Wright-Giemsa staining. The cell cycle and apoptosis of NB4 cells after TPA treatment were detected by flow cytometry. The mRNA expressions of NB4 cells after TPA treatment were analyzed by high-throughput microarray analysis and real-time quantitative PCR. Western blot was used to detect the protein expression of CDKN1A, CDKN1B, CCND1, MYC, Bax, Bcl-2, c-Caspase 3, c-Caspase 9, PIK3R6, AKT and p-AKT. RESULTS: Compared with the control group, TPA could inhibit the proliferation of NB4 cells, induce the cells to become mature granulocyte-monocyte differentiation, and also induce cell G1 phase arrest and apoptosis. Differentially expressed mRNAs were significantly enriched in PI3K/AKT pathway. TPA treatment could increase the mRNA levels of CCND1, CCNA1, and CDKN1A, while decrease the mRNA level of MYC. It could also up-regulate the protein levels of CDKN1A, CDKN1B, CCND1, Bax, c-Caspase 3, c-Caspase 9, and PIK3R6, while down-regulate MYC, Bcl-2, and p-AKT in NB4 cells. CONCLUSION: TPA induces NB4 cell cycle arrest in G1 phase and promotes its apoptosis by regulating PIK3/AKT signaling pathway.
Assuntos
Leucemia Promielocítica Aguda , Humanos , Caspase 3/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Caspase 9/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína X Associada a bcl-2/metabolismo , Linhagem Celular Tumoral , Divisão Celular , Apoptose , RNA Mensageiro , Proliferação de CélulasRESUMO
PURPOSE: Esophageal cancer is the most common gastrointestinal tumor and is difficult to be eradicated with conventional treatment. Porphyrin-based photosensitizers (PSs) mediated photodynamic therapy (PDT) could kill tumor cells with less damage to normal cells. As the most widely used porphyrin-based photosensitizer in clinics, Photofrin II has excellent anti-tumor effect. However, it has some disadvantages such as weak absorption at near infrared region, the complexity of components and prolonged skin photosensitivity. Here series novel 5,15-diaryl-10,20-dihalogeno porphyrin derivatives were afforded and evaluated to develop more effective and safer photosensitizers for tumor therapy. METHODS: The photophysical properties and singlet oxygen generation rates of 5,15-diaryl-10,20-dihalogeno porphyrins (I1-6, II1-4) were tested. The cytotoxicity of I1-6 and II1-4 were measured by MTT assay. The pathway of cell death was studied by flow cytometry. In vivo photodynamic efficacy of I3 and II2-4 in Eca-109 tumor-bearing BABL/c nude mice were measured and histopathological analysis were examined. RESULTS: 5,15-Diaryl-10,20-dihalogeno porphyrins I1-6 and II1-4 were synthesized. The longest absorption wavelength of these halogenated porphyrins (λmax = 660 nm) displayed a red shift around 30 nm compared to the unhalogenated porphyrins PS1 (λmax = 630 nm). The singlet oxygen generation rates of I1-6 and II1-4 were significantly higher than PS1 and HMME. All PSs mediated PDT showed obvious cytotoxic effect against Eca-109 cells compared to HMME in vitro and in vivo. Among these PSs, II4 exhibited appropriate absorption in the phototherapeutic window, higher 1O2 generation rate (k = 0.0061 s-1), the strongest phototoxicity (IC50 = 0.4 µM), lower dark toxicity, high generation of intracellular ROS in Eca-109 cells and excellent photodynamic anti-tumor efficacy in vivo. Besides, cell necrosis was induced by compound II4 mediated PDT. CONCLUSION: All new compounds have obvious photodynamic anti-esophageal cancer effects. Among them, the photosensitizer II4 showed excellent efficacy in vitro and in vivo, which has the potential to become a photodynamic anti-tumor drug.
Assuntos
Antineoplásicos , Neoplasias Esofágicas , Fotoquimioterapia , Porfirinas , Animais , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Neoplasias Esofágicas/patologia , Camundongos , Camundongos Nus , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Porfirinas/uso terapêutico , Oxigênio Singlete/uso terapêuticoRESUMO
The determination of lumbopelvic alignment is essential for planning adult spinal deformity surgery and for ensuring favorable surgical outcomes. This prospective study investigated the correlation between the lumbar section of lumbar spine lordosis and increasing pelvic incidence in 324 Asian adults with a mean age of 55 ± 13 years (range: 20-80 years), comprising 115 male and 209 female volunteers. Participants were divided into three groups based on pelvic incidence (G1, G2, and G3 had pelvic incidence of < 45°, 45-55°, and ≥ 55°, respectively). We determined that distal and proximal lumbar lordosis contributed differentially to the increase in pelvic incidence, whereas the lordosis ratio of the L3-L4 and L4-L5 segments mostly remained constant. The mean contribution ratio of the segmental lordosis from L1 to S1 was as follows: L1-L2, 2.3%; L2-L3, 11.7%; L3-L4, 18.1%; L4-L5, 25.2%; and L5-S1, 42.7%. Pelvic incidence had a stronger correlation with proximal lumbar lordosis than did distal lumbar lordosis. The ratios of proximal lumbar lordosis to distal lumbar lordosis were 37.8% in G1, 45.8% in G2, and 55.9% in G3. These findings serve as a reference for future lumbar spine correction or fusion surgery for Asian adults.
Assuntos
Lordose , Fusão Vertebral , Adulto , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Lordose/diagnóstico por imagem , Lordose/epidemiologia , Lordose/cirurgia , Estudos Prospectivos , Posição Ortostática , Radiografia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Estudos RetrospectivosRESUMO
Cu-based catalysts have been widely used for water-gas shift reaction (WGS, CO + H2O â CO2 + H2), and α-MoC support also shows the good performance for the reaction. Therefore, WGS reaction is systematically studied over Cu/α-MoC by using density functional theory (DFT). DFT result shows the strong metal-support interaction between Cu and α-MoC(111) support. As a result, an extensive tensile strain is introduced in the Cu lattice due to α-MoC support, and Cu 3d band center shifts to Fermi level. However, the strong metal-support interaction does not lead to significant polarization of the Cu/α-MoC surface due to the less charge transfer from Mo to Cu. For the WGS reaction, small Cu particles on α-MoC(111) are likely to facilitate the reaction. At the interface of Cu-α-MoC(111), oxygen stabilizes the dissociated *H, which is benefit of H2O scission. Then, the activity increases compared with Cu(111) surface. In general, small Cu particles on α-MoC support also have good activity for WGS reaction compared with Au deposition on α-MoC. Graphical abstract.
RESUMO
BACKGROUND: Acacia catechu (L.f.) Willd (ACW) and Scutellaria baicalensis Georgi (SBG) are two famous herbs and often used in many traditional Chinese compound prescriptions. In clinical practice, ACW-SBG couple as a famous traditional herb couple, was widely used for treating infantile cough, phlegm and fever which caused by pulmonary infection. Meanwhile, a standardized bioflavonoid composition-UP446 with ACW extract and SBG extract has been used in both special nutritional products and joint care dietary supplements. However, its herb-herb interactions based on absorption, distribution, metabolism and excretion (ADME) study had not been investigated. PURPOSE: The aim of this study was to evaluate potential pharmacokinetic, tissue distribution and excretion interactions between ACW and SBG, and to provide useful information for the development of suitable dosage forms and clinical applications. STUDY DESIGN AND METHODS: A sensitive and reliable LC-MS/MS method was established to the quantification of four major bioactive components in rat biological samples. The method was validated for accuracy, precision, linearity, range, selectivity, lower limit of quantification (LLOQ), recovery, and matrix effect. All validation parameters met the acceptance criteria according to regulatory guidelines. Based on this, we obtained and compared the parameters about pharmacokinetics, tissue distribution and excretion of four major bioactive components in this study. RESULTS: This work revealed that the parameters including plasma pharmacokinetics, tissue distribution and excretion of (+)-catechin (C), (-)-epicatechin (EC), baicalin (BL) and baicalein (BLE) in single administration had significant differences compared co-administration. The results illustrated that interactions between two herbs are related to the effect of competitive gastrointestinal absorption inhibition and drug metabolism by liver metabolic enzymes. Moreover, the alteration of C and EC in the tissue of lung maybe could enhance the pharmacological activity for treating pulmonary infection. CONCLUSION: This is the first report to evaluate the pharmacokinetics, tissue distribution and excretion of co-administration of ACW or SBG to rats and compared its properties of four major bioactive components. The results demonstrate that herb -herb interactions occurred in this herb couple.
Assuntos
Acacia/química , Medicamentos de Ervas Chinesas/farmacocinética , Extratos Vegetais/química , Extratos Vegetais/farmacocinética , Animais , Catequina/análise , Catequina/farmacologia , Cromatografia Líquida , Interações Medicamentosas , Medicamentos de Ervas Chinesas/química , Flavanonas/análise , Flavanonas/farmacocinética , Flavonoides/análise , Flavonoides/farmacocinética , Limite de Detecção , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Scutellaria baicalensis , Espectrometria de Massas em Tandem/métodos , Distribuição TecidualRESUMO
Currently, patients with co-infection with HIV and tuberculosis are treated with more than one drug. PA-824 a new chemical entity and a member of a class of compounds known as nitroimidazo-oxazines, has significant antituberculosis activity and a unique mechanism of action. Darunavir (PrezistaTM) is a new protease inhibitor of HIV-1. A simple, sensitive and rapid LC-MS-MS method has been developed and validated for simultaneous determination of PA-824 and darunavir. Chromatographic separation was achieved on Agilent Eclipse plus C18 column (100 mm × 2.1 mm, 3.5 µm) using gradient elution of acetonitrile-water (90:10, v/v) with fast gradient elution at a flow rate of 0.6 mL/min and run time of 4.5 min. The mass spectrometer was run in positive electrospray ionization mode using multiple reaction monitoring to monitor the mass transitions. The method was validated for accuracy, precision, linearity, range, selectivity, lower limit of quantification, recovery and matrix effect. All validation parameters met the acceptance criteria according to regulatory guidelines. The method had been successfully applied to a pharmacokinetic study of fixed dose administration of PA-824, darunavir and their combination in rats. The results indicated that when co-administration of darunavir could decrease the amount of PA-824 in vivo and extend the elimination half-life.
Assuntos
Cromatografia Líquida/métodos , Darunavir/farmacocinética , Nitroimidazóis/farmacocinética , Espectrometria de Massas em Tandem/métodos , Animais , Darunavir/sangue , Darunavir/química , Interações Medicamentosas , Modelos Lineares , Nitroimidazóis/sangue , Nitroimidazóis/química , Ratos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
The present study investigated the possible antiobesity and hypoglycemic effects of phloretin (Ph). In an attempt to discover the hypoglycemic effect and potential mechanism of Ph, we used the streptozotocin-induced diabetic rats and (L6) myotubes. Daily oral treatment with Ph for 4 weeks significantly (P<0.05) reduced postprandial blood glucose and improved islet injury and lipid metabolism. Glucose consumption and glucose tolerance were improved by Ph via GOD-POD method. Western blot results revealed that the expression of Akt, PI3K, IRS-1, and GLUT4 were upregulated in skeletal muscle of type 2 diabetes (T2D) rats and in L6 myotubes by Ph. The immunofluorescence studies confirmed that Ph improved the translocation of GLUT4 in L6 myotubes. Ph exerted hypoglycemic effects in vivo and in vitro, hence it may play an important role in the management of diabetes.