PHARMAZIE
·
2018
·Vol. 73
·期 6
·329-334
·
IF 1.016
Darbalaei Sanaz,Zhang Xinlin,Wang Nanxi,Qin Yanjie,Han Xuemei,Rang Ying,Zhai Xuejia,Lu Yongning
Aprepitant (APT), an antiemetic drug belonging to the class of substance P antagonists is efficiently used in both acute and delayed chemotherapy-induced nausea and vomiting. Nausea and vomiting induced by imatinib (IMA) as a chemotherapeutic drug could be reduced by APT. This study
investigated the effect of APT on the pharmacokinetics of IMA and its major metabolite N-desmethyl imatinib (N-D IMA) in rats and the mechanism of this drug-drug interaction. The results indicated that after 3 days of pretreatment with APT (10 mg/kg), the blood concentration of IMA was decreased
in both of oral and intravenous routes of IMA administration compared to vehicle treated rats, whereas the blood concentration of N-D IMA was not significantly changed. The total clearance (CL/F) of oral and intravenous given IMA was increased by 1.41 and 1.32-fold, and the bioavailability
was greatly decreased about 30.43% and 24.40% respectively. At this time, the P-gp and the hepatic CYP3A1 were increased at both the mRNA and protein levels. These results demonstrated that ingestion of APT will decrease the bioavailability of IMA to a significant extent in rats and the drug-drug
interaction between APT and IMA appears to be due to modulation of P-gp and CYP3A1.
研究领域:
药理学
·
肿瘤学
·
药学
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产品关联
DOI
PubMed
高影响因子
PHARMAZIE
·
2016
·Vol. 71
·期 3
·134-138
·
IF 1.264
Ning Yuming,Rao Yuefeng,Yu Zhenwei,Liang Wenquan,Li Fanzhu
The aim of this study was to evaluate the skin permeability of anemonin, which was extracted from the Chinese herb weilingxian , and its potency of relieving the inflammation caused by rheumatoid arthritis (RA). To optimize the formulation, the solubility of anemonin in water
and selected concentration of ethanol-water vehicles was determined. The effect of ethanol on the permeation of anemonin through human skin was then studied. Additionally, the influences of hydroxypropyl methylcellulose E50 (HPMC) and Carbomer 934 in different concentrations on the permeation
of drug were investigated. Finally, the anti-inflammatory effect of the optimized formulation was assessed by murine model of xylene-induced ear edema. The results showed that the solubility and transdermal permeation of anemonin in ethanol-water vehicles linearly depended on the ethanol concentration.
The combination of 30% ethanol and 3% Azone had a synergistic enhancement effect and was therefore selected for gel preparation. The 0.14% anemonin gel prepared with 1% HPMC exhibited the highest transdermal flux. The xylene-induced ear edema inhibitory rate of the optimized formulation was
48.85%. The results indicated that transdermal administration of anemonin is a potential modality for combating inflammation caused by RA.
研究领域:
药理学
·
中药学
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产品关联
DOI
高影响因子
PHARMAZIE
·
2021
·Vol. 76
·期 10
·499-502
·
IF 1.267
Tao Lijun,Chen Lina,Pei Yanmin,Ma Ping,Xu Qingbin,Wang Jialing,Yu Yang,Cheng Jiang,Zhou Ru
The aim of this study was to investigate the vasodilatory effects of betaine, an alkaloid isolated from Lycium barbarum, on isolated pulmonary artery rings in rats and its possible mechanisms. Pulmonary vessels of normal Sprague–Dawley rats were isolated and pre-contracted
using norepinephrine. Then, betaine was cumulatively added in differing concentrations (0.02-0.14 mg/mL), and the tension curve was observed and recorded. Changes in the tension of the pulmonary artery rings with an intact endothelium and a dissected endothelium were recorded. The interactions
among betaine and NG-nitro-L-arginine methyl ester, indomethacin, 4-aminopyridine, barium chloride, and glibenclamide were evaluated. The experimental results show that betaine can relax the pulmonary artery rings pre-contracted by norepinephrine. Furthermore, pre-incubation with NG-nitro-L-arginine
methyl ester and indomethacin did not inhibit betaine vasodilation, demonstrating that vasodilation by betaine is endothelium-dependent. Additionally, pretreatment of pulmonary artery rings with 4-aminopyridine and glibenclamide had no effect on betaine. However, pretreatment of pulmonary
artery rings with barium chloride attenuated the effects of betaine. In conclusion, the vasodilatory effects of betaine on pulmonary artery rings is associated with inward rectifier potassium channels.
研究领域:
药理学
·
心血管研究
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DOI
PubMed
高影响因子
PHARMAZIE
·
2021
·Vol. 76
·期 10
·503-506
·
IF 1.267
Pan Liuliu,Zhang Xiaodan,Wang Danhan,Huang Min,Huang Qiusui,Duan Ping,Mei Jie
Discovering compounds with anti-cervical cancer effect and clarifying their targets will help promoting the precise treatment of cervical cancer. The present study intended to clarify the effect of osthole on cervical cancer cells, and to explore the possibility of DCLK1 as its target.
Annexin V-PE staining and flow cytometry methods were used to determine cell apoptosis. Meanwhile, apoptosis related biomarkers were probed by immunoblotting. The MTT assay was employed to study the effect of osthole in combined with or without LRRK2-IN-1 (a DCLK1 inhibitor) on cell proliferation.
Then, combination index was determined. To examine the interaction of osthole with DCLK1, molecular docking was carried out. Based on the biological database from cBioPortal, the association between DCLK1 and clinical manifestations of cervical cancer were evaluated. The results showed that
osthole can significantly induce apoptosis of HeLa and Me-180. When combined with LRRK2-IN-1, the effect of osthole on cell proliferation was antagonized, suggesting that it might competitive binding to DCLK1. Furthermore, molecular docking showed that osthole interacts with Val468 residues
of DCLK1 to form hydrogen bonds. The analysis of database showed that DCLK1 frequently mutant and deleted in cervical cancer, and is related to cell survival, tumor progression and recurrence. However, no obvious correlations were found between DCLK1 and lymphatic metastasis/differentiation.
In conclusion, osthole significantly inhibits the survival of cervical cancer cells. It's probably target DCLK1 mechanistically via interacting with Val468. DCLK1 could be a potential therapeutic target for cervical cancer.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
PHARMAZIE
·
2021
·Vol. 76
·期 11
·544-550
·
IF 1.267
Lu Mengru,Liang Junli,Liang Jinyu,Li Hepeng,Yang Peng
The neurotoxicity of amyloid-β (Aβ) and its deposition in neurons plays a critical role in the occurrence and development of Alzheimer's disease (AD). Several preclinical experiments have found that the renin inhibitor aliskiren has a wide range of physiological effects, including
hindering the progression of atherosclerosis and anti-inflammatory. This study is aimed to explore the effect of aliskiren on neuronal toxic damage and the underlying mechanism. This study established an in vitro nerve injury model through Aβ 1-42 induction; the effects
of aliskiren on the viability, inflammatory damage and apoptosis of SH-SY5Y cells were examined. For the sake of explore the underlying mechanism; SwissTargetPrediction website and molecular docking were utilized to predict the target of aliskiren. Then the impacts of the target protein overexpression
were determined to verify its mediation. The results of the current study demonstrate that aliskiren has no effect on the viability of SH-SY5Y cells while Aβ1-42accumulation could significantly downregulate cell viability. In addition, aliskiren could alleviate neuronal inflammatory
damage and apoptosis arise from Aβ 1-42accumulation. Following confirming the high expression level of the predicted target PDE4B in damaged cells, it was found that PDE4B overexpression can reverse the influence of aliskiren on cell viability, inflammatory damage and apoptosis.
In conclusion, aliskiren upregulates cell viability, reduces inflammatory damage and apoptosis induced by Aβ accumulation in AD via inhibiting PDE4B. These findings have expanded the scope of future application of aliskiren and provided a theoretical basis.
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DOI
PubMed
高影响因子
PHARMAZIE
·
2018
·Vol. 73
·期 12
·729-732
·
IF 1.016
Wang YB.,Sun B.,Han B.
Malignant melanoma is a highly lethal disease, and advanced stages of melanoma have proven to be resistant to many chemotherapeutic drugs including temozolomide and paclitaxel. Cancer stem cells (CSCs) have been identified and isolated in different cancers including melanoma, and have
been proven playing important role in the drug resistance. Retinoic acid (RA) is a promising anticancer agent, which can induce differentiation of CSCs. The main purpose of the present study was to evaluate the possible RA-induced differentiation of melanoma CSCs and sensitization of melanoma
CSCs to paclitaxel. Our results show that CSCs of human melanoma A375 cells was more tolerant to paclitaxel than other non-CSCs melanoma cells. On the contrary, RA had stronger inhibitory effect on melanoma CSCs than on non-CSCs. At the same time, RA could arrest the cell cycle of CSCs and
reduce the expression of Sox-2, Oct-4 in CSCs of melanoma, thereby induced the differentiation of CSCs and increased its sensitivity to paclitaxel. With this study we concluded that RA increases the anticancer effect of paclitaxel by inducing differentiation of cancer stem cells in melanoma,
and the combined application of RA and paclitaxel may be more effective in the treatment of melanoma.
研究领域:
肿瘤学
·
细胞生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
PHARMAZIE
·
2023
·Vol. 78
·期 5
·31-36
·
IF 1.6
Xiaowei J.,Lijuan Y.,Yanling L.,Qiuxiao L.,Bohong G.
The purpose of this study was to combine carbon nanotube with ethosomes in order to obtain hybrid nanocarriers for transdermal delivery of ketoprofen (KP). KP-loaded functionalized single-walled carbon nanotube (f-SWCNTs) composite ethosomes (f-SWCNTs-KP-ES) were designed and were verified
by a series of characterizations. The particle size of the preparation is less than 400 nm. DSC and XRD experiments showed that KP existed in an amorphous state after it was adsorbed and loaded on f-SWCNTs. TEM experiments showed that the structure of SWCNTs remained intact after oxidation
and modification by PEI. FTIR results showed that PEI were successfully modified on the surface of SWCNT-COOH, and KP was successfully loaded on f-SWCNTs. In vitro release characteristics showed that the preparation had sustained release behavior and conformed to the first-order kinetic
equation model. In addition, f-SWCNTs-KP-ES gel were prepared and in vitro skin permeation and in vivo pharmacokinetics were studied. The results showed that f-SWCNTs-KP-ES gel could enhance the skin permeation rate of KP and increase the drug retention of drugs in the skin.
The characterization results consistently showed f-SWCNTs is a promising drug carrier. The hybrid nanocarrier prepared by the combination of f-SWCNTs and ethosomes can enhance the transdermal absorption of drugs and improve the bioavailability of drugs, which has a certain significance for
the development of advanced hybrid nano-preparations.
研究领域:
药剂学
·
纳米医学
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
PHARMAZIE
·
2023
·
IF 1.6
Yan Weifeng,Cui Zhe,Li Wenxin,An Xin,Cheng Xu,Wang Sihong,Jin Chunmei
New anti- Toxoplasma gondii agents are in demand due to the emergence of high toxicity. Ginseng polysaccharides and saponins can be used to treat the replication of Toxoplasma gondii in an attempt to determine whether the medicinal uses of ginseng are supported by pharmacological
effects. Anti- Toxoplasma gondii activities of ginseng polysaccharides and saponins were examined in vitro and in vivo. The findings are the survival time and rate of Toxoplasma gondii infected mice after the intake of the total polysaccharides and saponins increased
compared to untreated control mice. The survival rate of mice treated with ginseng saponins was the highest at 83.3%, the phenomenon of splenomegaly of mice was decreased especially ( p < 0.05) treated with ginseng polysaccharides. Accordingly, ginseng polysaccharides and saponins
have a potential application in anti-Toxoplasma gondii treatments.
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DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2018
·
IF 4.556
Mingliang Pei,Xu Jia,Guoping Li,Peng Liu
Facile approach has been developed for the versatile polymeric microspheres with tumor microenvironment bioreducible degradation, pH-activated surface charge reversal, pH-triggered “off-on” fluorescence, and drug release via emulsion copolymerization of glycidyl methacrylate (GMA), poly(ethylene glycol) methyl ether methacrylate (PEGMA), and N-rhodamine 6G-ethyl-acrylamide (Rh6GEAm) with N,N-bis(acyloyl)cystamine) (BACy) as disulfide cross-linker and functionalization. The final PGMA-DMMA microspheres showed excellent cytocompatibility, pH-triggered surface charge reversal at pH 5–6, strong fluorescence only in acidic media, and bioreducible degradation with high reductant level, indicating their promising application as theranostic nanoplatforms for precise imaging-guided diagnosis and chemotherapy. The DOX-loaded PGMA-DMMA microspheres with a drug-loading capacity of 18% and particle size of about 150 nm possessed unique pH/reduction dual-responsive controlled release, with a cumulative DOX release of 60.5% within 54 h at the simulated tumor microenvironment but a premature leakage of <8.0% under the simulated physiological condition. Enhanced inhibition efficacy against HepG2 cells was achieved compared to free DOX.
研究领域:
生物材料
·
肿瘤学
·
纳米医学
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产品关联
DOI
PubMed
高影响因子
CLEAN-Soil Air Water
·
2015
·Vol. 44
·期 1
·72-77
·
IF 1.945
Qun He,Ruijuan Qu,Xinghao Wang,Zhongbo Wei,Ping Sun,Zunyao Wang
Although it has been widely known that arsenic poses great threat to organisms and arsenic species account for the toxic effect of the metalloid, relatively little attention has been given to the arsenic toxicity to different organisms at different pH values. Three kinds of aquatic organisms including Photobacterium phosphoreum , Daphnia magna , and Danio rerio were used to study the effects of pH on the toxicity of arsenic. Toxicity test results were analyzed by calculating EC 50 values and for arsenic species at five different pH values (5.0, 6.0, 7.0, 8.0, and 9.0). As a result, As(III) is more toxic to the tested organisms than As(V), and P. phosphoreum was more sensitive to the toxicity of arsenic than D. magna and D. rerio . The toxicity of As(III) species is different for different organisms: dihydrogen arsenite, H 2 AsO 3 – , is more toxic to P. phosphoreum and D. rerio than arsenous acid, H 3 AsO 3 , while H 3 AsO 3 is more toxic to D. magna . As for As(V), arsenate, HAsO 4 2− , is the most toxic to P. phosphoreum , whereas dihydrogen arsenate, H 2 AsO 4 – , may be responsible for the toxicity to D. magna and D. rerio . As(III) and As(V) are more toxic to P. phosphoreum in an alkaline environment, while for D. magna in an acidic environment and As(III) is more toxic to D. rerio in an alkaline environment and As(V) in an acidic environment.
研究领域:
环境生物学
·
毒理学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Sensor and Energy Materials
·
2022
·
IF 0
Jia Gao,Rui-Yang Zhao,Yi-Guang Wang,Ruo-Chen Xie,Wei Wang
We present a fluorescent microscopic method using an ultra-pH-sensitive polymeric probe to rapidly map within subsecond the pH distribution resulting from oxygen reduction reaction electrocatalysed by an array of platinum nanoparticles. Upon voltammetry of the surface-supported Pt catalysts, fluorescent quenching waves are observed to depend on the electrode potential. The spatiotemporal fluorescent evolution is then confirmed under a constant potential control to be due to the local pH change as a function of diffusing time by an estimation of the proton diffusion coefficient ( L α t 1 / 2 ) . On these bases, the fluorescent measurements at short reaction times can provide quantitative information regarding the one and two dimensional pH distributions, which are shown to exhibit the expected shape of a typical diffusion-driven concentration gradient. Such imaging of proton/pH profiles may find important applications such as efficient screening of different micro/nanoscale electrocatalysts.
研究领域:
分析化学
·
电化学
·
材料科学
·
生物传感器
✓ 已验证
DOI
Nanoscale
·
2016
·Vol. 9
·期 1
·314-325
·
IF 7.76
Lijia Li,Wei Sun,Lian Li,Yuanyuan Liu,Lei Wu,Fengling Wang,Zhou Zhou,Zhirong Zhang,Yuan Huang
Cationic materials have been reported as promising tools for targeting to mitochondria which are the “power houses” and “metabolic garbage keepers” of cells. However, their positive nature also restricts their in vivo application due to the quick clearance. Herein, we fabricated a nanohybrid consisting of the pH-responsive N-(2-hydroxypropyl)methacrylamide (HPMA) co-polymer (R-P) shells and positive mesoporous silica nanoparticle cores via electrostatic interaction. The anticancer drug, docetaxel (DTX), was encapsulated in the positive MSN cores (MSN–DTX). Once concealed by the anionic R-P shield, the assembled nanohybrid R-P@MSN–DTX will achieve prolonged blood circulation thereby leading to an enhanced EPR effect. At mildly acidic tumor environmental pH, first-stage charge reversion took place due to the hydrolysis of the amide bond on HPMA co-polymers. The de-attachment of the HPMA co-polymer occurred because of the positive charge repulsion and partial exposure of the positively charged MSN core promoted the cell internalization. The second-stage pH-responsiveness in the endo/lysosomes with a more acidic environment accelerates the disassembly of the nanohybrid and the leakage of the core facilitated the endo/lysosome escape and mitochondrial targeting with the help of intracellular compartmental acidity. Gathering up the characteristics of neutralized charge and stepwise pH-responsiveness, the R-P@MSN–DTX acquired a good tumor inhibition rate of 72.6% on nude mice. Our report provided a reference for systemic mitochondrial targeting achieved by the union of “assembly–disassembly”.
研究领域:
药学
·
纳米技术
·
癌症研究
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DOI
PubMed
高影响因子
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