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Content comparison on quercetin from different parts and HPLC fingerprint of Lespedeza cuneata(Dum.Cours.)G.Don.

Hua FENG ; Yingbo LIU ; Liang LIU ; Niansong PAN ; Dequan ZHOU

Journal of International Pharmaceutical Research.2016;43(5):980-984. doi:10.13220/j.cnki.jipr.2016.05.033

Objective To establish a HPLC method for the determination of quercetin from different parts of L. cuncata(Dum. Cours.)G.Don.,including roots,old branches,young shoots,leaves and seeds,and to build the fingerprints. Methods The HPLC method determination of quercetin and fingerpints were establised. Results The restults showed that there were great differences be?tween the quercetin contents from different parts,with the highest contents found in seeds,followed by young shoots,leaves,old branches,and roots. The similarities of HPLC fingerprints of the medicinal material were quite different from the parts of L. cuncata (Dum.Cours.)G.Don.. The similarities were all above 0.95 for L. cuncata(Dum.Cours.)G.Don. samples,roots,old branches and young shoots below 0.85,leaves and seeds similarities below 0.60. Conclusion It was concluded that different parts(such as roots, old branches,young shoots,leaves,seeds)of L. cuncata(Dum.Cours.)G.Don. should be divided in clinical and productive practice so as to supply the scientific basis for enhancing the curative effect and reasonable utilization of the resource of L. cuncata(Dum.Cours.)G. Don.

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Establishment of LC-MS/MS method for the determination of forsklin in rat plasma and its pharmacokinetics

Dianwei SONG ; Decai WANG ; Zhiyun MENG ; Ruolan GU ; Meihui SHI ; Zhuona WU ; Jingze WANG ; Guifang DOU

Journal of International Pharmaceutical Research.2012;(2):149-153. doi:10.3969/j.issn.1674-0440.2012.02.010

Objective To develop a sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the determination of forsklin in rat plasma.Methods After extraction with methyl tert-butyl ether,chromatographic separation was performed on a C18 column with the mobile phase consisting of water ( 0.1％ formic acid)-acetonitrile in a gradient elution mode.A tandem mass spectrometer equipped with electrospray ionization (ESI) source was used as detector in the positive ion mode.Quantification was performed using multiple reaction monitoring (MRM) with the precursor product combination ions of m/z 411→375.3 and 285→193 for forsklin and diazepam.Results Good linearity was obtained in the 0.5-1000 ng/ml range for the analyte and the analytical method was validated in terms of specificity,precision,accuracy,recovery,stability and matrix effect.These assays gave RSD values always lower than 14.4％ and RE values between -3.5 ％ and 3.8％.In addition,the specificity,extraction recovery,stability and matrix effect were satisfactory.Conclusion Due to its high sensitivity,specificity and simplicity,the method could be used for pharmacokinetic studies of forsklin.

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Determination of aconitine in dog tissue homogenates by HPLC-MS/MS and its application to in vitro metabolic stability study

Cuiping YANG ; Sha LIAO ; Tianhong ZHANG ; Jinglai LI ; Xiaoying WANG ; Jinxiu RUAN ; Zhenqing ZHANG

Journal of International Pharmaceutical Research.2012;(3):256-260. doi:10.3969/j.issn.1674-0440.2012.03.015

Objective To develop a HPLC-MS/MS method for the determination of aconitine and study thein vitro metabolic stability of aconitine in dog tissue homogenates.Methods The chromatographic separation was performed on a C18 column.The mobile phase consisted of acetonitrile and water with 0.2％ formic acid and 5 mmol/L ammonium acetate.A triple quadrupole tandem mass spectrometer equipped with an electrospray ionization interface source was used for the quantitative determination in the positive selective reaction monitor mode.Aconitine was incubated with dog tissue homogenates and samples were withdrawn at different time points and precipitated by acetonitrile with internal standards citalopram.Results Aconitine showed good linear relationship over the range from 5 to 500 ng/ml.The recoveries of aconitine were between 85.73％ and 92.12％ at three QC concentration levels.The intra- and inter-day precisions were 5.32％ - 8.95％ and 5.45％ - 8.86％,respectively.After incubation,about 20％ of aconitine were cleared in the liver and small intestine,and t1/2 were 460.6 and 521.3 min,respectively.But none was metabolized in the stomach and kidney.Conclusion These results demonstrated that aconitine was mainly metabolized in the liver and small intestine at a slow rate.

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PD-1/PD-L1 signaling pathway and its application in tumor

Shi WANG ; Longlong LUO ; Ming LV ; Yuanfang MA

Journal of International Pharmaceutical Research.2015;(2):143-147. doi:10.13220/j.cnki.jipr.2015.02.003

PD-1/PD-L1 signaling pathway as a T cell immune response co-stimulatory signaling pathway plays an important role in adaptive immunity. PD-1 is a major co-receptor expressing on T cells, binding with its ligands(PD-L1 and PD-L2), PD-1 can inhibit T cell activation and protect the body against the attacks from its own immune system. In addition to adjusting and maintaining autoimmune tolerance, in tumor cells PD-L1 expression is up-regulated, while in the virus-infected T cells PD-L1 expression is also upregulated. PD-1 / PD-L1 are involved in the tumor and infectious pathogen immune evasion, thus blocking the PD-1 / PD-L1 signaling pathway has become a hot research of cancer and chronic diseases. Currently, there are several anti-PD-1 or PD-L1 monoclonal antibodies approved by the FDA to enter clinical studies, which have shown significant anti-cancer effect.

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Overviews and analysis of the U.S. FDA′s new approvals in the 2016 second half year

Zhongming TANG

Journal of International Pharmaceutical Research.2017;44(1):74-80. doi:10.13220/j.cnki.jipr.2017.01.013

In the second half of 2016,the U.S. Food and Drug Administration(FDA)approved 7 new molecular entities and 3 new Biologic License Application(BLA), the lowest number in recent years. According to the prescription information for profes-sionals,this article introduced the description,mechanism of action and clinical studies and briefly describes the boxed warning,indi-cations and usage,dosage and administration,dosage form and strength,contraindications,warning and precautions,adverse reac-tions,drug interaction and the use in the special population. In addition,the first and critical events in the history of new drug develop-ment and reaserch were emphasized.

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Small-molecule inhibitors of anthrax toxin

Aihua NIE ; Wei GU ; Jingjing LIU

Journal of International Pharmaceutical Research.2017;44(1):1-12. doi:10.13220/j.cnki.jipr.2017.01.001

Anthrax is a malignant infectious disease caused by Bacillus anthracis spores,after entering the host Bacillus an-thracis produces and releases anthrax toxin,which is the main cause leading to death of the host. The anthrax toxin is composed of two enzymatically active components:lethal factor(LF)and edema factor(EF),and one shared receptor binding and translocation com-ponent:protective antigen(PA). PA combined with LF is called lethal toxin(LeTx),while PA combined with EF called edema toxin (EdTx). Currently,the main drugs for treating anthrax are antibiotics,but antibiotics can only kill part of anthrax spores and bacte-ria,and cannot inhibit the activity of anthrax toxin. So it is necessary to develop novel drugs for inhibiting anthrax toxin. This review summarizes the evolution of small-molecule inhibitors of anthrax toxin respectively targeting PA,LF and EF.

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Light-inducible CRISPR/Cas9 system for control of gene expression:research advances

Liting LAN ; Xiaoli WEI ; Haitao YAN ; Ruibin SU

Journal of International Pharmaceutical Research.2017;44(3):215-219. doi:10.13220/j.cnki.jipr.2017.03.001

Cas9 is a RNA-guided double stranded DNA nuclease that participates in the CRISPR/Cas9 system. Wide-type Cas9 directly silences the expression of target gene by gene splicing. The engineered dCas9 protein with the mutation at D10A and H840A lacks the Cas9' s endonuclease function but keeps its DNA binding activity. dCas9 can activate special genes by fusing with transcription activator. Meanwhile,it can inhibit the gene transcription by directly binding to the target gene and stop gene transcrip?tion. Combination of light sensitive structures and CRISPR can produce light-inducible CRISPR/Cas9 system for control of gene expres?sion. This system is able to activate or inhibit gene expression via the use of controlling blue light(470 nm). In this review,we mainly discuss the development of the light inducible CRISPR/Cas9 system as well as its application in the control of gene expression.

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Effects of quercetin on suppressing migration and invasion of A549 cells via the STAT3 signaling pathway

Huayang LI ; Jing XU ; Hui NA ; Shuhui WANG

Journal of International Pharmaceutical Research.2017;44(3):262-266. doi:10.13220/j.cnki.jipr.2017.06.009

Objective To investigate the effect of quercetin on suppressing the proliferation,migration and invasion of A549 cells via the signal transducer and activator of transcription 3(STAT3)signaling pathway. Methods The A549 cells were cultured in vitro and treated with quercetin at various concentrations(0,7.5,15,30,60 and 120μmol/L)for 24 h,48 h and 72 h. The proliferation of A549 and the 50%inhibitory concentration(IC50)were measured by the cell counting kit-8(CCK-8). The A549 cells treated for 24 h were randomly divided into 4 groups:the blank control,15 and 30 μmol/L quercetin,and 3 μg/ml cisplatin(the positive control) groups. The effect of quercetin on adhesion rate was detected by the cell adhesion assay;the cell migration ability was evaluated by the wound healing assay;the cell invasion ability was evaluated by the Transwell chamber assay;the expression of STAT3 and phosphory?lated-STAT3(p-STAT3)proteins were detected by Western blot assay. Results Quercetin inhibited A549 cell growth dose-depend?ently. Compared with the blank control group,quercetin could significantly inhibit the adhesion rate,migration ability and invasion of A549 cells(P<0.05 or P<0.01);compared with the blank control group,quercetin significantly inhibited STAT3 and p-STAT3 ex?pression level(P<0.05 or P<0.01). Conclusion Quercetin could inhibit the proliferation,migration and invasion of A549 cells, and the mechanism is libely related to the STAT3 signal pathway.

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Epigenetics-based anticancer drugs:research advances

Ming WANG ; Xue LI ; Ziling WANG

Journal of International Pharmaceutical Research.2016;43(4):658-664. doi:10.13220/j.cnki.jipr.2016.04.013

In recent years,with the completion of the Human Genome Project and the development of mapping the Human Ge?nome Methylation Variable Site Map Plan,research on epigenetics and the generation and deveopment of cancer,epigenetic treatment drugs,especially the successful clinical application of the DNA methyltransferase and histone deacetylation inhibitors in the treatment of cancer patients,epigenetic has becoming a hot spot. This article reviews the recent progress in pharmacological action of epigenetics-based anticancer drugs,it may provide some new ideas to the therapy and fundamental research of cancer.

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Overview of China′s pediatric drug situation and regulatory policy

Hongjie XIAO ; Mengdie ZHOU ; Yang SUN ; Wu ZHONG

Journal of International Pharmaceutical Research.2016;43(4):579-584. doi:10.13220/j.cnki.jipr.2016.04.001

Pediatric drug accessibility has become a global problem,pediatric drug shortages and off-label uses are very seri?ous. In China,lack of suitable varieties,appropriate dosage forms and specifications,weak foundations on clinical trials,irregular prescribing behavior and irrational drug use and other issues on pediatric drugs are still outstanding. To improve pediatric drug accessi?bility,it may need all aspects work together,that is,cooperation of the national macro-policy support,participation of enterprises and medical institutions,to establish realistic goals and programs to address pediatric drug problem. This paper studies the foreign pediat?ric regulation measures and policies and by comparing foreign policies to China′s current situation,we can find out the problems and defects,give appropriate advice,in order to provide advice and reference to promote the development of pediatric drug.

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