FOLIA MICROBIOLOGICA
·
2015
·Vol. 61
·期 3
·249-253
·
IF 1
Hu Ruixue,Du Na,Chen Nan,Lin Li,Zhai Yanhua,Gu Zemao
The mechanisms of resistance to levofloxacin for Aeromonas hydrophila isolated from diseased fish and selected in vitro were examined in this study. Levofloxacin-resistant mutants were obtained by selection of A. hydrophila in vitro. The quinolone resistance-determining regions (QRDRs) of the gyrA and parC genes were sequenced in Lev R strains and reverse mutation strains. All Lev R strains carried a point mutation at codon 83 (Ser → Ile), and one strain (25 %) harbored a mutation at position 92 (Leu → Met) in the GyrA-QRDR. After being transferred in a levofloxacin-free medium, one strain of the mutants was successfully reversed and the reversion was related with mutations o f GyrA-QRDR at positions 81 (Gly → Asp) and 83 (Ile → Ser). No amino acid alteration was found in the ParC-QRDR. In addition, the minimum inhibitory concentration (MIC) of levofloxacin for the mutants was lower in the presence of reserpine, and all mutants were also resistant to some of the other quinolones. It was found that the mechanism of levofloxacin resistance of A. hydrophila selected in vitro was related to gyrA of type II topoisomerase, and an efflux mechanism was involved in the resistance as well.
研究领域:
微生物学
·
分子生物学
·
药理学
·
水产病害防治
·
抗菌药物耐药性
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DOI
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2016
·Vol. 12
·期 2
·202-208
·
IF 0
Huiyan Shi,Chenzhi Hou,Liqiang Gu,Zhe Wei,Hang Xing,Meiyu Zhang,Shixiao Wang,Longshan Zhao,Kaishun Bi,Xiaohui Chen
The present study was designed to investigate the influence of the pretreatment of piperazine ferulate on pharmacokinetic parameters of methotrexate in methotrexate-induced renal injury rats. A simple and efficient high performance liquid chromatography coupled with mass spectrometry (HPLC-MS) method was developed to determine methotrexate in rat plasma. Methotrexate and syringic acid (internal standard) were extracted from rat plasma samples by protein precipitation with acetonitrile. The analysis was performed on a CAPCELL PAK C 18 column (150 mm × 4.6 mm, 5 µm) with acetonitrile and 5 mmol/l ammonium acetate aqueous (10:90, v/v ). The linear range was 5.0 × 10 −2 to 100.0 µg/ml for methotrexate. Other parameters were all within the acceptance criteria. The validated method was successfully applied the pharmacokinetic study of methotrexate between two methotrexate treated groups (with and without the pretreatment of piperazine ferulate). Compared with the methotrexate treated alone group, the pharmacokinetic parameters in the methotrexate with the pretreatment of piperazine ferulate group showed significantly lower MRT (0-t) , MRT (0-∞) and T 1/2 . Results suggested that methotrexate can be rapidly eliminated, cleared or metabolized in rat blood, which might be related to the pretreatment of piperazine ferulate. The method provided deeper insights into rational clinical use of methotrexate with the pretreatment of piperazine ferulate on cancer patients with renal dysfunction.
研究领域:
药理学
·
药物代谢
·
肾脏病学
·
肿瘤学
·
临床药学
·
分析化学
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DOI
JOURNAL OF FOOD BIOCHEMISTRY
·
2021
·Vol. 46
·期 1
·e14007
·
IF 2.72
Jing Liu,Zhongan Zhu,Yuhang Yang,Michael Adu-Frimpong,Lin Chen,Hao Ji,Elmurat Toreniyazov,Qilong Wang,Jiangnan Yu,Ximing Xu
A liposome of Licochalcone A (LCA-Liposomes) was purposively prepared to ameliorate the low in vivo availability and efficacy of LCA. Physical characterization of LCA-Liposomes was carried out mainly by determining particle size, morphology, zeta potential (Z-potential), and efficiency of LCA encapsulation (EE) via appropriate techniques. Also, the rate of LCA release in vitro and distribution in vivo (plasma and tissues) was evaluated. Evaluation of the antirenal activity of LCA-liposomes was carried out by establishing chronic renal failure (CRF) model in mice through intragastric administration of adenine (200 mg/kg) and subsequent determination of biochemical parameters and examination of tissue sections. Respectively, the mean size of liposomal particles, Z-potential and EE of LCA-Liposomes were 71.78 ± 0.99 nm, −38.49 ± 0.06 mV, and 97.67 ± 1.72%. Pharmacokinetic and tissue distribution studies showed that LCA-Liposomes could improve the availability of LCA in the blood and tissues, whereas during pharmacodynamics studies, the liposome effectively improved the therapeutic effect of LCA on CRF mice by potentially protecting the renal tissues while exhibiting antioxidant activity. In conclusion, LCA-Liposomes could effectively improve the bioavailability of LCA and provide platform for the development of LCA-related functional products. Practical applications As a traditional Chinese medicine, licorice is widely used in food and pharmaceutical industries. LCA is a small molecule flavonoid extracted from the root of licorice. In this study, LCA was loaded on liposome carriers, which significantly improved the water solubility and oral bioavailability, and proved that LCA-Liposomes have certain therapeutic effects on chronic renal failure, thereby providing a basis for the development of LCA into drugs or functional food in the future.
研究领域:
药剂学
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药理学
·
分子药理学
·
药物代谢
·
纳米医学
·
中药药理学
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DOI
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2015
·Vol. 2015
·期 1
·239749
·
IF 1.88
Zhiping Wang,Junbiao Wu,Qun Zhou,Yifei Wang,Tongsheng Chen
Berberine (Ber), an isoquinoline derivative alkaloid and active ingredient of Coptis, has been demonstrated to possess antidiabetic activities. However its low oral bioavailability restricts its clinical application. In this report, Ber nanosuspension (Ber-NS) composed of Ber and D- α -tocopheryl polyethylene glycol 1000 succinate (TPGS) was prepared by high pressure homogenization technique. Antidiabetic effects of Ber-NS relative to efficacy of bulk Ber were evaluated in streptozotocin (STZ) induced diabetic C57BL/6 mice. The particle size and zeta potential of Ber-NS were 73.1 ± 3.7 nm and 6.99 ± 0.17 mV, respectively. Ber-NS (50 mg/kg) treatment via oral gavage for 8 weeks resulted in a superior hypoglycemic and total cholesterol (TC) and body weight reduction effects compared to an equivalent dose of bulk Ber and metformin (Met, 300 mg/kg). These data indicate that a low dosage Ber-NS decreases blood glucose and improves lipid metabolism in type 2 diabetic C57BL/6 mice. These results suggest that the delivery of Ber as a nanosuspension is a promising approach for treating type 2 diabetes.
研究领域:
药剂学
·
药理学
·
分子药理学
·
药物递送系统
·
糖尿病研究
·
药物代谢
·
纳米医学
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DOI
高影响因子
JOURNAL OF MOLECULAR RECOGNITION
·
2016
·Vol. 30
·期 1
·e2566
·
IF 2.091
Hua-jin Zeng,Min Miao,Ran Yang,Ling-bo Qu
In this study, the fibrillation of hen egg-white lysozyme (HEWL) in the absence and presence of different concentrations of silybin was studied by thioflavin T spectroscopy, Congo red binding assays, 8-anilino-1-naphthalenesulfonic acid (ANS) fluorescence assay, circular dichroism, and transmission electron microscopy. The experimental results indicated that not only the fibrillation of HEWL at high temperature (65°C) and low pH (pH = 2.0) could be inhibited effectively by silybin but also the inhibition of HEWL by silybin followed a dose-dependent manner. Molecular docking studies indicated that 2 possible binding modes could be found in the interaction between silybin and HEWL via van der Waals forces and electrostatic forces as well as hydrogen bonding. One of these 2 conformations was directly entered into the cavity of HEWL (binding site I); the other was bound to the surface of HEWL (binding site II). In this way, silybin could not only increase the hydrophobicity of the cavity or the surface of HEWL but also influence the microenvironment of the binding site, which was able to stabilize the structure of HEWL and delay the process of HEWL fibrosis.
研究领域:
生物化学
·
分子生物学
·
蛋白质科学
·
药理学
·
结构生物学
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DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Hong-Bo Yang,Jie-Yu Song,Chan Xu,Jin Li,Chan Zhang,Sun Xie,Chun-li Teng
Pueraria lobata, commonly known as kudzu, is a medicinal and food plant widely used in the food, health food, and pharmaceutical industries. It has clinical pharmacological effects, including hypoglycemic, antiinflammatory, and antioxidant effects. However, its mechanism of hypoglycemic effect on type 2 diabetes mellitus (T2DM) has not yet been elucidated. In this study, we prepared a Pueraria lobata oral liquid (POL) and conducted a comparative study in a T2DM rat model to evaluate the hypoglycemic effect of different doses of Pueraria lobata oral liquid. Our objective was to investigate the hypoglycemic effect of Puerarin on T2DM rats and understand its mechanism from the perspective of metabolomics. In this study, we assessed the hypoglycemic effect of POL through measurements of FBG, fasting glucose tolerance test, plasma lipids, and liver injury levels. Furthermore, we examined the mechanism of action of POL using hepatic metabolomics. The study's findings demonstrated that POL intervention led to improvements in weight loss, blood glucose, insulin, and lipid levels in T2DM rats, while also providing a protective effect on the liver. Finally, POL significantly affected the types and amounts of hepatic metabolites enriched in metabolic pathways, providing an important basis for revealing the molecular mechanism of Pueraria lobata intervention in T2DM rats. These findings indicate that POL may regulate insulin levels, reduce liver damage, and improve metabolic uptake in the liver. This provides direction for new applications and research on Pueraria lobata to prevent or improve T2DM.
研究领域:
药理学
·
代谢组学
·
内分泌学
·
天然产物研究
·
中医药
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DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2015
·
IF 2.912
Jianbo Xiao,Petra Högger
Most data of bioactivity from dietary polyphenols have been derived from in vitro cell culture experiments. In this context, little attention is paid to potential artifacts due to chemical instability of these natural antioxidants. An early degradation time (CT10) and half-degradation time (CT50) were defined to characterize the stability of 53 natural antioxidants incubated in Dulbecco’s modified Eagle’s medium (DMEM) at 37 °C. The degree of hydroxylation of flavones and flavonols significantly influenced the stability in order resorcinol-type > catechol-type > pyrogallol-type, with the pyrogallol-type being least stable. In contrast, any glycosylation of polyphenols obviously enhanced their stability. However, the glycosylation was less important compared to the substitution pattern of the nucleus rings. Methoxylation of flavonoids with more than three hydroxyl groups typically improved their stability as did the hydrogenation of the C2═C3 double bond of flavonoids to corresponding flavanoids. There was no significant correlation between the antioxidant potential of polyphenols and their stability. Notably, the polyphenols were clearly more stable in human plasma than in DMEM, which may be caused by polyphenol–protein interactions. It is strongly suggested to carry out stability tests in parallel with cell culture experiments for dietary antioxidants with catechol or pyrogallol structures and pyrogallol-type glycosides in order to avoid artifacts.
研究领域:
食品科学
·
分子生物学
·
生物化学
·
营养生物化学
·
药理学
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DOI
高影响因子
Chemical Biology & Drug Design
·
2020
·Vol. 97
·期 3
·565-571
·
IF 2.548
Bin Sun,Jiahao Wang,Luohua Liu,Longfei Mao,Lizeng Peng,Yuwei Wang
A series of indirubin derivatives hydrochloride were obtained using a convenient and mild method from indirubin. The newly synthesized compounds and their derivatives were characterized by 1 H NMR, 13 C NMR, and MS. Furthermore, we tested their IDO1 enzyme inhibitory activity and anti-proliferative activities in K562 tumor cells. The experimental results revealed that some of the compounds showed potential anti-enzyme and anti-tumor activity. Among of them, compound 4b exhibited certain inhibitory activity on IDO1 (IC 50 : 29.52 μmol/L), and compound 4a displayed activity similar to indirubin in K562 tumor cells (IC 50 : 24.96 μmol/L). This type of indirubin derivative is expected to have the potential to act as an immunologically active anti-tumor drug, indicating that further research will be worthwhile.
研究领域:
药物化学
·
肿瘤学
·
药理学
·
药物发现
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DOI
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2021
·Vol. 2021
·期 1
·5574413
·
IF 2.63
Cui He,Lihua Yu,Wenran Dan,Surong Deng,Haidong Ma,Beizhong Liu,Yuan Li
This study aimed to develop a simple microfluidic chip analysis technology to study the inhibitory effect of protocatechuic acid on shear-induced platelet aggregation. The microfluidic chip designed in this study simulates 80% fixed narrow microchannels. This microchannel narrow model uses the finite element analysis module of the three-dimensional modeling software solidwork to analyze fluid dynamic behavior. Blood treated with protocatechuic acid at 1, 2, 4, 8, or 16 µ g/mL was passed through the microchannel stenosis model at a shear rate of 10,000 s −1 . The platelet adhesion and aggregation behaviors were then measured using fluorescence microscopy and observed in real time. Simultaneously, the antiplatelet aggregation effect of protocatechuic acid was analyzed using thromboelastography and photoelectric turbidimetry. The designed stenosis model of the microfluidic chip can produce a gradient of fluid shear rate, and the gradient of fluid shear rate can induce platelet aggregation. Under this model, the degree of platelet adhesion and aggregation increased as the shear rate increased. In the experimental concentration range of 0–8 µ mol/mL, protocatechuic acid exerted a concentration-dependent inhibition of platelet aggregation. In contrast, thromboelastography and photoelectric turbidimetry failed to demonstrate an inhibitory effect. The microfluidic chip analysis technology developed in this study can be used to study the effect of protocatechin in inhibiting platelet aggregation induced by shear rate in vitro. This technology is simple to operate and can be used as a new type of antiplatelet aggregation analysis technology for screening studies of novel potential antiplatelet aggregation drugs.
研究领域:
生物医学工程
·
血液学
·
药理学
·
微流控技术
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DOI
高影响因子
Journal of Global Antimicrobial Resistance
·
2016
·
IF 1.087
Dongmei Wu,Ruochen Lu,Yuquan Chen,Jie Qiu,Chaocheng Deng,Qiang Tan
This study aimed to determine whether selection by antibiotics, chlorhexidine (CHX) and Rhizoma coptidis extract (RCE) would lead to cross-resistance or decreased susceptibility in Staphylococcus aureus . The S. aureus reference strain ATCC 25923 as well as 14 clinical isolates were exposed to antibiotics, CHX and RCE at sublethal doses for up to 14 days. Changes in susceptibility were determined by analysis of minimum inhibitory concentrations (MICs). All isolates were cross-resistant to more than one other antibiotic following tetracycline exposure, and increased resistance (≥4-fold MIC increase) to RCE and CHX was observed in six and three isolates, respectively. Following selection by CHX, most of the treated strains showed no significant change in sensitivity to CHX. However, all strains developed cross-resistance to at least one antibiotic, and decreased susceptibility (≥4-fold MIC increase) to RCE appeared in seven strains. Following exposure to RCE, 11 isolates showed cross-resistance to at least one antibiotic. In addition, three RCE-exposed strains showed reduced susceptibility to CHX (4- or 8-fold MIC increase). The results obtained in this study imply that antibiotics, biocides and antimicrobial Chinese herbs might employ some of the same mechanisms of action against bacteria, triggering mutual cross-resistance to further foster the development of bacterial resistance.
研究领域:
微生物学
·
感染病学
·
药理学
·
分子生物学
·
抗菌药物耐药性
·
天然药物学
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DOI
高影响因子
RSC Advances
·
2015
·Vol. 5
·期 100
·82153-82158
·
IF 3.84
Wei-ping Hu,Guo-dong Cao,Jin-hua Zhu,Jia-zhong Li,Xiu-hua Liu
Batatasins are endogenous plant hormones found in yams and other related plant species. These plants are widely consumed as botanical dietary supplements in many parts of the world. This study investigated the inhibitory effects and mechanisms of Batatasin I, III, IV, V against α-glucosidase regarding their antidiabetic activities. The results revealed that Batatasin I, III, IV inhibited α-glucosidase in a reversible and noncompetitive manner, with IC50 values of 2.55, 1.89 and 2.52 mM respectively, while Batatasin V completely abolished its inhibitory activity even at the highest concentrations tested. Furthermore, a class of Batatasin-derived compounds with different substitution patterns was synthesized and subjected to the assay to clarify the structure–activity relationships, which suggested that the hydroxyl at the C-2′ position may play a significant role in improving the inhibitory activities. Their probable binding modes and the specificity of the binding sites were studied using molecule docking simulation. It was concluded that Batatasins, especially Batatasin III and IV, are promising α-glucosidase inhibitors, which therefore could be used as functional food to alleviate postprandial hyperglycemia and as potential candidates for the development of antidiabetic agents.
研究领域:
天然产物化学
·
药理学
·
分子生物学
·
药物代谢
·
功能食品
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DOI
高影响因子
Journal of Analytical Methods in Chemistry
·
2022
·Vol. 2022
·期 1
·2565494
·
IF 2.594
Qiulong Zhao,Chunxue Wang,Jiaxin Cheng,Hui Yan,Ling Wang,Dawei Qian,Jinao Duan
According to the sixth edition of China’s “New Coronavirus Diagnosis and Treatment Plan (NCDTP),” ReDuNing injection (RDN) was firstly introduced to treat severe and critical COVID-19, whereas its combination with broad-spectrum antibiotics was suggested to take with extreme caution and full reasons. Therefore, we aim to describe the pharmacokinetics of seven active phytochemicals and semiquantification of nine relevant metabolites in ReDuNing injection (RDN) after combining with cefuroxime sodium (CNa) for injection in rat plasma. Male Sprague–Dawley rats were randomly assigned to six groups, and they were intravenously administered, respectively, with different prescriptions of RDN (2 mL/kg) and CNa (225 mg/kg). At different time points (0.03, 0.08, 0.17, 0.24, 0.33, 0.50, 0.67, 1, and 6 h) after administration, the drug concentrations of iridoids glycosides, organic acids, and metabolites in rat plasma were determined using ultrahigh-pressure liquid chromatography coupled with linear ion rap-orbitrap tandem mass spectrometry (UHPLC–LTQ–Orbitrap–MS), and main pharmacokinetic parameters were estimated by noncompartment model. The results showed that there were differences in pharmacokinetic parameters, AUC (0-t) , T 1/2 , C max , CL of iridoids glycosides, and organic acids, after the intravenous administration of the different combinations of RDN and CNa. Moreover, different combinations of the injections also resulted in different curves of relative changes of each metabolite. The obtained results suggested that RDN and CNa existed pharmacokinetic drug–herb interactions in rats. The findings not only lay the foundation for evaluating the safety of RDN injection combined with CNa but also make contributions to clinically applying RDN injection combined with CNa, which works potentially against severe forms of COVID-19.
研究领域:
药理学
·
药物代谢
·
中药学
·
临床药学
·
分析化学
·
病毒学
·
转化医学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）