Table of Content

26 May 2017, Volume 26 Issue 5

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Review

Phytochemistry and bioactivities of sesquiterpenoids from the Artemisia species

Laibin Zhang, Jinao Duan, Jieli Lv

2017, 26(5):  317-334.  DOI: 10.5246/jcps.2017.05.034

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The genus Artemisia is one of the largest and most widely distributed genera of the family Compositae. One type of the mainly active metabolites found in the Artemisia plants is sesquiterpenoids with extensive biological activities, including anti-inflammatory, immunomodulatory, anti-tumour, antimalarial, antinociceptive, antimicrobial and other activities. In this review, wecomprehensively summarized the progressconcerning the phytochemistry and biological activities of sesquiterpenoids obtained from the Artemisiaspecies from 2010 to July 2016. Furthermore,several future research perspectives and development of sesquiterpenoids as potential therapeutic agents were discussed as well.



Original articles

Holistic quality evaluation of Panax notoginseng extract and injection using an UPLC-QTOF-MSE based metabolomics approach

Yiyi Zhao, Hongzhu Guo, Yougen Chen, Xintong Fu

2017, 26(5):  335-345.  DOI: 10.5246/jcps.2017.05.035

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In the present study, we established an UPLC-QTOF-MS^E based metabolomic approach in order to evaluate the holistic qualities and compare the quality difference by finding characteristic components of Panax notoginseng extracts (PNE) and Xuesaitong (XST) injection samples from different manufacturers. The data were processed through unsupervised principal component analysis (PCA) and supervised orthogonal partial least squared discrimination analysis (OPLS-DA) to compare the quality differences. Two-dimensional PCA score plots showed a tendency to separate the XST injections and extracts, and most XST injection samples were clearly clustered into two groups. Especially, the injections from He and YB companies were distinguishedinto two groups. In addition, only injection samples of Hu company were near the cluster of PNE. To explore the potential chemicalcomponents contributing most to the differences between XST injection samples from different manufacturers and PNE, an S-plotwas constructed following the OPLS-DA. Ginsenoside Rd, ginsenoside Rg₁, ginsenoside Re, ginsenoside Rb₁, 20(S)-ginsenoside Rh₁, gypenoside VII, ginsenoside Rg₂, ginsenoside Rh₄, ginsenoside Rk₁ or Rg₅, notoginsenoside Fc, 20(R)-ginsenoside Rg₃, ginsenoside F₂ and protopanaxadiol were recognized as characteristic chemical markers that contributed most to reflect the difference between XST injections and PNE. Ginsenoside Rd, ginsenoside Rg₁, ginsenoside Re, ginsenoside Rb₁ and gypenoside VII were revealed as index components contributing most to the differences of PNE and XST injections, and quantitative analysis of these components could ensure the consistent quality of XST injections. Based on the fact that the injections should be standardized with the characteristic components as quality control chemical markers, it is most important to keep the quality of extracts of raw materials stable and reliable.



Simultaneous determination of 10 nucleosides and nucleobases from different cultivation years of Fritillaria unibracteata var. wabuensis by HPLC-DAD

Feng Pan, Wei Wu, Pinli Dong, Bo Hu, Lingliang Guan, Ling Shu

2017, 26(5):  346-354.  DOI: 10.5246/jcps.2017.05.036

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Determination of nucleosides and nucleobases is important for the quality control of Fritillaria unibracteata Hsiao et K.C. Hsia var. wabuensis (FUW) due to their physiological and pharmacologicalactions. In the present study, we developed a sensitive and reliable HPLC-diode-array detection method to simultaneously determine ten nucleosides and nucleobases, including cytosine, uracil, cytidine, uridine, thymine, adenine, inosine, guanosine, thymidine and adenosine. Complete separation of all the analytes was achieved on a Zorbax 300 Å 300 Extend C₁₈ column with a gradient of methanol-ultrapure water at a flow rate of 1 mL/min in less than 30 min. The diode-array detector wavelength was set at 260 nm for the UV detection of nucleosides and nucleobases. The optimized method provided good linearity (R²≥0.9993 for all the analytes), satisfactory precision (RSD≤3.715%), good repeatability (RSD≤3.748%) and good recovery (RSD from 97.688% to 102.923%). In addition, the developed method was successfully applied to simultaneous determination of ten nucleosides and nucleobases from FUW, and their content changes of various cultivation time (1-7 years) were further analyzed for the first time. Our findings were useful for ensuring the cultivation time choice of artificial cultivation, quality control, pharmaceutical studies and clinical efficacy of FUW. 



DNA methyltransferase inhibitor dramatically alters the secondary metabolism of Pestalotiopsis microspora

Dengfeng Yang, Fenglou Liu, Xiaolong Yang

2017, 26(5):  355-359.  DOI: 10.5246/jcps.2017.05.037

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5-Azacytidine, a DNA methyltransferase inhibitor, led to significant changes in the secondary metabolism of the plant endophytic fungus, Pestalotiopsis microspora. Analysis of the culture broth extract led to the isolation of a new compound, 4′-formamidophenyl-5-methoxybenzoate (1), along with seven known polyketides, 4-hydroxybenzoic acid (2), LL-P880α (3), 1′-hydroxy-4-methoxy-6-pentyl-2H-pyran-2-one (4), pestalotiollide B (5), pestalotiopyrone G (6), endocrocin (7) and 2′-hydroxy-6′-hydroxymethyl-4′-methylphenyl-2,6-dihydroxy-3-(2-isopentenyl)benzoate (8). HPLC profiles revealed that all compounds except for 4 belonged to the newly induced secondary metabolites. In addition, all compounds were proved to be devoid of significant antifungal activity in the bioassays.



Chemical constituents from the aerial parts of Tirpitzia ovoidea

Xueyan Yang, Yifan Zhang, Wen Zhang, Dan Su, Mingying Shang, Guangxue Liu, Feng Xu, Shaoqing Cai

2017, 26(5):  360-365.  DOI: 10.5246/jcps.2017.05.038

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In the present study, we isolated 18 known compounds from Tirpitzia ovoidea (Linaceae), including seven terpenoids (1-7), three simple phenylproponoids (8-10), three coumarins (11-13) and five other compounds (14-18). The structures of these compounds were identified by spectroscopic methods and compared with those reported in the literature. Compounds 1-16 were isolated from this plant as well as the Linaceae family for the first time.



Analysis on molecular interaction mechanism of four hapten flavonoids in Shuang-huang-lian powder injection with bovine serum albumin

Haixiu Jiang, Yanqing Guan, Xiaotian Zhang, Ya Han, Ningning Guo, Hong Wang, Shizhong Chen

2017, 26(5):  366-371.  DOI: 10.5246/jcps.2017.05.039

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Baicalein, baicalin, scutellarin and Chrysin-7-O-β-D-glucuronide are the major flavonoids of the Shuang-huang-lian powder injection. These flavonoids are thought to be haptens that can induce allergic reactions. The interaction mechanism of these haptens with bovine serum albumin (BSA) was investigated by surface plasmon resonance (SPR) and molecular modeling method. The SPR study indicated that these compounds could specifically bind to the BSA with one binding site and equilibrium dissociation constant (K_D) values were determined. Molecular modeling explored the mechanism of interaction under simulated physiological condition. The result of molecular modeling indicated that flavonoids could bind with BSA in the hydrophobic pocket of sub-domain II with hydrogen bonding as the main acting force.



Synthesis of the arsenic-containing amino-acids, and their potential applications in peptide chemistry

Yajuan Shi, Qinghua Guan, Yanfen Wu, Chao Wang

2017, 26(5):  372-378.  DOI: 10.5246/jcps.2017.05.040

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Trivalent organoarsenic compounds have attracted a great deal of interest because of their potential antineoplastic activities. In this work, we synthesized a series of arsenic-containing amino acid analogues by introducing the structure of 1-arsino-2,6,7-trithiobicyclo[2.2.2]octane to the side chain of modified amino acid derivatives. The protected amino acid (6a) as a typical objective compound was applied in peptide synthesis via the classic procedures for the formation of peptide bond or removal of protecting groups. Our results showed that the application of compound 6a (or 5a) in the peptide chemistry was satisfactory.



Drug administration and clinical pharmacy column

Safety of ivabradine, a heart rate lowering drug: a systematic review and meta-analysis

Ruirui Xiao, Xiuqin Xu, Lei Sun, Xiaolei Fang, Peng Xiao

2017, 26(5):  379-389.  DOI: 10.5246/jcps.2017.05.041

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As a novel heart rate lowing agent, ivabradine can reduce the heart rate by inhibiting the I_f (pacemaker) current in the sinoatrial node without affecting blood pressure or left ventricular systolic function. However, the safety of ivabradine remains controversial. In the present work, we aimed to assess any risk of cardiovascular mortality, bradycardia, phosphenes and atrial fibrillation associated with the ivabradine administration by meta-analysis. Studies were retrieved from PubMed, EMBASE, MEDLINE, Web of Science, Cochrane, www.clinicaltrials.gov web site and related conferences. Randomized controlled trials comparing ivabradine with comparators were identified and analyzed. Two reviewers independently extracted relevant informationfrom the eligible trials and processed the data. This meta-analysis was performed by using Review Manager (5.3) and Stata (14.1) software. Moreover, sensitivity analysis and publication bias of the included studies were evaluated. A total of 12 randomized controlled trials meeting the inclusion criteria were included. Results of the meta-analysis revealed that there was no significant difference between ivabradine group and control groups in cardiovascular mortality (RR = 0.97, 95% CI: 0.89-1.06, P = 0.49). While the administration of ivabradine was associated with a significant increase in the incidence of bradycardia (RR = 3.90, 95% CI: 2.47-6.17, P<0.00001) and phosphenes (RR = 4.95, 95% CI: 3.24-7.55, P<0.00001) as well as atrial fibrillation (RR = 1.24,95% CI: 1.07-1.43, P = 0.003). High quality of the included studies was confirmed by quality assessment. No publication bias was observed, and sensitivity analysis confirmed that the obtained results were stable. In conclusion, the meta-analysis proved that the use of ivabradine was associated with a significant increase in the risk of bradycardia, phosphenes and atrial fibrillation. Therefore, clinicians need to take these risks into account when using ivabradine in treatment. 



Framework and local experience of pharmaceutical reimbursement criteria policy (PRCP) in China

Jiaxuan Yu, Mengyuan Que, Shuai Wang, Ting Yin, Jianfeng Wang, Song Yang, Bin Jiang

2017, 26(5):  390-394.  DOI: 10.5246/jcps.2017.05.042

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In the present study, we compared local policies in Chongqing, Zhejiang, Anhui, Fujian and Sanming and summarized connotation and framework of PRCP. Moreover, we proposed that China should make PRCP at the provincial level, strengthen connection with other health care reform policies under tripartite system reform, such as equivalence evaluation of quality and efficacy of generics, and evaluate policy effects timely to improve the policy.