Table of Content

30 April 2018, Volume 27 Issue 4

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Review

The development and application of peroxisome proliferator-activated receptor (PPAR) modulator

Jian Xin, Xiangnan Xu, Yuping Wang, Zhentao Zhang, Yuheng Ma

2018, 27(4):  215-228.  DOI: 10.5246/jcps.2018.04.023

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The peroxisome proliferator-activated receptors (PPARs), PPARα, PPARβ/δ and PPARγ, are ligand-activated transcriptional factors, which belong to the nuclear receptor super family and play crucial roles in glucose and lipid metabolism. Based on the impressive advantages of PPAR agonists (like TZD and fibrate compounds) in the treatment of metabolic syndrome and type 2 diebetes, PPAR modulators have doubtlessly grabbed much more attention. However, serious clinical adverse effects, especially for PPARγ agonists, hinder the development of PPAR agonist. Therefore, the selectivity and safety would be the key points and have been taken into the consideration for novel generation PPAR agonist research, and then several dual- or pan-PPAR modulators have emerged. Furthermore, experimental study indicates that partial agonists can neutralize the side effect and achieve modest therapeutic effect. This review summaries structural features of PPAR receptors, illustrates the method of PPAR modulator design, then lists and analyzes recent dual- and pan- agonists.



Original articles

Construction of folate-conjugated epirubicin liposomes for enhancing the cellular uptake and the co-localization with nuclei of invasive breast cancer cells

Yingzi Bu, Limin Mu, Lei Liu, Wanliang Lu

2018, 27(4):  229-240.  DOI: 10.5246/jcps.2018.04.024

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Drug resistance of anthracycline in the invasive cancer is associated with the lowered cellular drug uptake and diminished co-localization of drug with nuclei. In the present study, we aimed to construct the folate-conjugated epirubicin liposomes by incorporating a synthesized folate-lipid derivative; and to assess the effects on cellular drug uptake, co-localization of drug with nuclei and efficacy in treatment of invasive breast cancer cells. The studies were performed on invasive human breast cancer cells. The folate-PEG₂₀₀₀-DSPE conjugate was synthesized, and the constructed folate-conjugated epirubicin liposomes were approximately 100 nm in size. The in vitro studies demonstrated that the folate-conjugated epirubicin liposomes had the strongest cellular drug uptake and co-localization with nuclei of the invasive breast cancer cells. Besides, the liposomes displayed the most significant efficacy in killing the invasive cancer cells, in preventing their invasive potential, and in penetrating ability into breast cancer spheroid as well. In conclusion, the constructed folate-conjugated epirubicin liposomes were able to enhance the efficacy in treatment of invasive breast cancer by improving the cellular drug uptake and increasing the co-localization with nuclei, hence offering a new strategy for potentially eradicating the invasive breast cancer cells.



Biocatalytic bis-C-alkylation of phenolics using one-pot cascades with promiscuous C-glycosyltransferase and prenyltransferase

Dawei Chen, Lili Sun, Ridao Chen, Kebo Xie, Lin Yang, Jungui Dai

2018, 27(4):  241-250.  DOI: 10.5246/jcps.2018.04.025

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C-glycosylation and C-prenylation are two important C-C-bond forming reactions for preparation, diversification and structural modification of natural/unnatural products with pharmacological activities. Here, we described unprecedented enzymaticcascades to C-glycosylate/prenylate different acyl resorcinol derivatives in stepwise, one-pot reactions by combining two promiscuous enzymes, MiCGT, a C-glycosyltransferase, and AtaPT, a prenyltransferase. Five novel bis-C-alkylated products were obtained and structurally identified by MS and NMR spectroscopic data as well as comparison with the literature. This study provided a potential synthetic strategy for synthesizing structurally novel and diverse compounds bearing both C-glycosyl and C-prenyl moieties by a two-step, enzymatic bis-C-alkylation.



Study on chemical constituents of Apocynum venetum L. leaves by LC/MS and determination of the best harvest season

Lingkun Tong, Hong Wang, Xiaotian Zhang, Ningning Guo, Ya Han, Daidong Wang, Shizhong Chen

2018, 27(4):  251-262.  DOI: 10.5246/jcps.2018.04.026

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The dried leaves of Apocynum venetum L. (AVL) is a traditional Chinese medicine widely used as antihypertensive medicine in China. Accurate determination of its best harvest season is important for its effective and safe use. In the present study, we developed a reliable method based on high-performance liquid chromatography-diode array detector-electro spray ionization-ion trap-time of flight (HPLC-DAD-ESI-IT-TOF) mass spectrometry and HPLC-DAD for the identification and quantification of major components in AVL leaves. Quantitative analysis of 24 samples collected weekly helped monitor the changes of compounds dynamically in AVL leaves to determine the best harvest season. A total of 30 compounds were identified, including quinic acid, five phenolic acids and 24 flavonoids. For the first time, 16 compounds were selected as marker compounds and simultaneously monitored weekly instead of monthly during the growth of the plant. The results showed that in May the leaves had the highest amount of phenolic acids, flavonoids and total compounds. Therefore, May should be the best harvest season for AVL leaves, which was distinct from previous studies. The established method was validated to be simple, accurate and precise, and thus it was of great importance for determination of the best harvest season.



Simultaneous determination of two bioactive components of Huangqi Guizhi Wuwu Decoction in rat plasma using UPLC-MS/MS and its application to a pharmacokinetic study

Xinyu Chang, Guiming Guo, Zheng Fan, Honglei Wang, Yang Liu, Lijuan Han

2018, 27(4):  263-272.  DOI: 10.5246/jcps.2018.04.027

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A rapid, sensitive and selective UPLC-MS/MS method was developed to determine paeoniflorin and astragaloside IV. This method was validated via a pharmacokinetic study using rat plasma. The internal standard was clarithromycin. A simple one-step deproteinization procedure was used to prepare plasma samples. Separation was achieved on a CAPCELL CORE ADME C₁₈ column with a gradient mobile phase consisting of solution A (water containing 0.1% formic acid) and solution B (acetonitrile) at a flow rate of 0.3 mL/min. Multiple reaction monitoring (MRM) was used with an electrospray ionization source (ESI) in positive mode. A good linear response was observed within the ranges of 0.01 to 5.00 μg/mL for paeoniflorin and 0.0001 to 0.05 μg/mL for astragaloside IV. The accuracy (RE) was within the range of –3.5% to 6.3%, and the intra- and inter-day precisions (RSD) were within 14.2%. The extraction recoveries were all above 78.9%. The pharmacokinetic study of the two analytes in rats after oral administration of Huangqi Guizhi Wuwu Decoction (HGWD) was successfully completed through this method. The method developed in this study will fill a gap in pharmacokinetic studies of HGWD.



HPLC-UV method for simultaneous determination of irbesartan, candesartan, gliquidone and pioglitazone in formulations and in human serum

Agha Zeeshan Mirza

2018, 27(4):  273-280.  DOI: 10.5246/jcps.2018.04.028

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In this study, we reported and validated a novel and sensitive reversed-phase liquid chromatographic method for the simultaneous determination of irbesartan, candesartan, gliquidone and pioglitazone. Separation was performed at 230 nm using a mobile phase consisting of methanol–water (90:10, v/v) with a flow rate of 1 mL/min. pH was adjusted to 3.5 with phosphoric acid. The concentration-response relationship was found linear over a concentration range of 5–25 μg/mL for all of the analytes tested. The limits of detection and quantification were 0.83 and 2.78 for irbesartan, 0.30 and 1.01 for candesartan, 1.11 and 3.93 for gliquidone, and 0.41 and 1.41 μg/mL for pioglitazone, respectively. Described method permitted the successful determination of these drugs in human serum. The developed method was simple, rapid, and it did not require extensive sample purification.



Drug administration and clinical pharmacy column

Statin therapy on pulmonary function in patients with COPD: a meta-analysis of randomized controlled trials

Yi Zhou, Jun Wang, Long Zhang

2018, 27(4):  281-288.  DOI: 10.5246/jcps.2018.04.029

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In thecurrent meta-analysis, we aimed to investigate the therapeutic effects of statins on pulmonary function inpatients with chronic obstructive pulmonary disease (COPD).MEDLINE, EMBASE and Cochrane Central Register of clinical trials were systematically searched until January 2017 for RCTs of statins. Only trials with COPD patients were included.The I² statistic was used to measure heterogeneity between trials and calculated mean differences for pulmonary function parameters with fixed-effect meta-analysis.Eighteligible studies with 534 participants were identified. Statin therapy had no remarkable influence on FEV1 (SMD –0.01, 95% CI –0.204 to 0.184, I²=0.0%, P = 0.922, n = 409), FEV1/ FVC (SMD 0.163, 95% CI –0.044to 0.369, I²=0.0%, P = 0.123, n = 364), 6MWD, heart rate or CRP. However, exercise time on treadmill was remarkably improved by statin therapy (SMD 1.271, 95% CI 0.930 to 1.612, I²=0.0%, P = 0.000, n = 160). Subgroup analysis showed significant, ameliorative effect of pravastatin on FEV1/FVC (SMD 0.362, 95% CI 0.049 to 0.674, I²=0.0%, P = 0.023).The results of this meta-analysis showed non-significant effect of statins on pulmonary function in COPD patients. Based on the studies reviewed, it is not recommended to prescribe statins for COPD patients without CVD risk factors due to lack of clearly defined benefit.



Short communication

Lignanoids from Solanum lyratum

Yunling Xu, Yajuan Xu, Haoxia Shi, Yue Liu, Tunhai Xu

2018, 27(4):  289-294.  DOI: 10.5246/jcps.2018.04.030

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In the present study, we aimed to investigate the chemical constituents from Solanum lyratum.The constituents were separated by column chromatography on silica gel, Sephadex LH-20 and preparative HPLC. Their structures were elucidated by spectroscopic means. A total of 13 compounds were isolated fromS. lyratumand identified as syringin (1), (+)-isolariciresinol (2), (+)-syringaresinol (3), leptolepisol D (4),(–)-secoisolariciresinol (5), (–)-epi-syringaresinol (6),aviculin(7), zhebeiresinol(8), ciwujiatone(9), (–)-(7′S,8S,8′R)-4,4′-dihydroxy-3,3′,5,5′-tetramethoxy-7′,9-epoxylignan-9′-ol-7-one(10),(+)-lariciresinol(11), (+)-pinoresinol (12) and (+)-medioresinol (13). All the compounds were isolated from S. lyratumfor the first time.