Journal of Chinese Pharmaceutical Sciences

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2013, 22(6): 463-466.

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Development of a high-content screening method to evaluate the cellular population-based biological activity of new siRNA delivering reagent

Yating Li, Yi Zheng, Delin Pan, Bo Xu, Yun Wu^*, Zhenjun Yang, Lihe Zhang

2013, 22(6): 467-474. DOI: 10.5246/jcps.2013.06.068

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Normally, cellular responses to modified siRNAs or new siRNA delivery systems have been studied in group cell behavior by PCR, western blotting and fluorescence microscopy. In this study, we present a novel high-content screening (HCS) strategy to evaluate a novel delivery system (named CLD) of siRNA therapeutics, with which both the content of intracellular siRNAs and changes in protein expressing levels have been quantified in group cells and cellular population. We also observed that with the better cell uptake, CLD provided siRNA therapeutics (siBraf) better antitumor capability. This novel strategy was proved to be with efficiency, accuracy and high competency to adherent cell lines, thus making siRNA research more simplified

Design, synthesis and pharmacological evaluation of caffeic acid phenethyl ester acylation as multifunctional neuroprotective agents against oxidative stress injury

Renzong Zhu, Xianling Ning, Zhili Zhang, Xiaowei Wang, Chao Tian, Junyi Liu^*

2013, 22(6): 475-482. DOI: 10.5246/jcps.2013.06.069

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4-Acylated or 3,4-diacylated caffeic acid phenethyl ester (CAPE) was prepared as prodrug to improve its stability and lipid solubility. Their neuroprotective activities were assessed by H2O2 model and 6-OHDA model. The results showed that target compounds displayed positive abilities to protect PC12 nerve cells from oxidative stress injury, superior to that of CAPE. Additionally, target compounds showed high blood-brain barrier permeability.

Cell cycle arrest effect of compound YSY-01A, a new proteasome inhibitor, on SK-OV-3 cells

Xuan Jia, Xia Yuan, Mingming Chu, Fuxiang Ran, Runtao Li^*, Jingrong Cui^*

2013, 22(6): 483-490. DOI: 10.5246/jcps.2013.06.070

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Compound YSY-01A, a recently synthesized proteasome inhibitor, has shown potent growth-inhibitory effect on tumor cells in previous researches. However, the mechanism of its inhibitory effects, especially on cell cycle, remains largely unclear. This study aimed to evaluate the correlation between cell cycle arrest effect of YSY-01A and its anti-cancer effect, and to probe the possible molecular mechanisms for its effects on human ovarian cancer SK-OV-3 cells. The results suggested that YSY-01A significantly (P<0.05) inhibited cellular proliferation of SK-OV-3 cells in a concentration-dependent and time-dependent manner. Furthermore, YSY-01A induced a G2/M cell cycle arrest of SK-OV-3 cells. Further investigation revealed that YSY-01A significantly (P<0.05) changed the expression levels of a series of cell cycle related protein, such as cyclin B1, cdc2, and p-cdc2 (T14). Meanwhile, YSY-01A could inhibit the TNF-α-induced NF-κB nuclear translocation and lead to the increase of IκBα as well as the decrease of IKK and Gadd45α. In conclusion, YSY-01A showed remarkable anti-cancer activity on SK-OV-3 cells, and its molecular mechanisms were related to G2/M cell cycle arrest.

Site- and orientation-specific binding of hematoporphyrin monomethyl ether to human serum albumin revealed by single spectral kinetic parameter

Luyong Zhang, Miao Zhang, Haixia Qiu, Ying Gu^*, Jingquan Zhao^*

2013, 22(6): 491-495. DOI: 10.5246/jcps.2013.06.071

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Interaction of a drug molecule with human serum albumin (HSA) is usually studied by fluorescence responses of the ligand or/and the single tryptophan residue (Trp-214) of the protein, but qualitative spectral information may lead to multiple conclusions. In this work, we report a study on the interaction of hematoporphyrin monomethyl ether (HMME) with human serum albumin (HSA), using the environment-sensitive spectra of HMME and reaction-induced fluorescence response of Trp-214. Particularly, the single kinetic parameter, the linear slope, was derived from the concentration-dependent absorbance or fluorescence of HMME in a certain solvent. A quantitative change in the slope at [HMME]/[HSA] = 1:1 clearly demonstrated a specific binding of HMME to site I. The microenvironment in site I may be comparable to that in DMSO solvent, because of the similarity of the slope. Linear correlation of the fluorescence to the absorbance of HMME in site I indicates that the energy transfer is not responsible for Trp-214 fluorescence quenching but an electron transfer may be possible. In addition, much higher rate observed for the binding of HMME or 2-taurine-substituted HB (THB) with HSA than that of hypocrellin B was due to the electrostatic attraction under physiological condition.

Statistical optimization and in vivo evaluation of colon specific delivery system of herbal rhubarb extract

Biraju Patel^*, Dhaval Patel, Jayant Chavda, Ravi Manek, Dhaval Mori

2013, 22(6): 496-502. DOI: 10.5246/jcps.2013.06.072

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The present research effort was aimed to develop colon targeted drug delivery system (CTDDS) of rhubarb, herbal drug using a mixed film of pectin and ethyl cellulose (EC). Pectin and ethyl cellulose were mixed in various proportions to coat the core tablet to target colon. The methanolic extract of rhubarb was used and the dose of the extract in each formulation was finalized by estimating the emodin content in it by high performace thin layer chromatography (HPTLC). In vitro drug release, erosion study in presence and absence of pectinase enzyme and release constant (K) of zero order was measured for each formulation. The formulation was optimized by using 3²full factorial design. Formulation having 50% pectin as a coating polymer with 12% coat weight was selected as an optimized formulation (OF) on the basis of % similarity with maximum desirability but this formulation was not able to retard the release of drug in stomach and upper intestine fully. So it was further coated with Eudragit S100 (ES) (3% coat weight). The optimized formulation, coated with ES indicated significant laxative activity on loperamide induced constipation in rats. The results revealed that CTDDS of rhubarb using two combined approaches of biodegrable microflora-activated system and pH-sensitive system exhibited a promising colon targeting performance.

Exploratory study on performance evaluation of drug administration at
provincial level in China

Ming Quan, Song Yang, Yanyan Li, Zhixian Hou, Bin Jiang*

2013, 22(6): 503-507. DOI: 10.5246/jcps.2013.06.073

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To construct a reliable indicator system to evaluate drug administration performance at provincial level in China, we referred to theories on government performance evaluation and practice of health performance evaluation, conducted field investigation, key person interview, fuzzy comprehensive evaluation and multi-round Delphi to build a three-dimensional evaluation indicator system of “input-process-outcome”. Weight of indicators was determined by the analytic hierarchy process (AHP). The related data were from Food and Drug Administration Statistical Yearbook for 2010 and China Statistical Yearbook for 2010. Thirty provinces were included in the rankings except Tibet for the unavailability of data. The ranking was highly accepted by officials from central and provincial drug administration agencies, which indicated the three-dimensional evaluation indicator system is feasible to assess drug administration performance at provincial level in China.

Efficacy and safety of fidaxomicin versus vancomycin for Clostridium difficile infection: systematic review and meta-analysis

Zhikang Ye, Huilin Tang, Jingli Duan, Suodi Zhai^*

2013, 22(6): 508-515. DOI: 10.5246/jcps.2013.06.074

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To compare the efficacy and safety of fidaxomicin and vancomycin for the treatment of patients with Clostridium difficile infection (CDI), randomized controlled trials (RCTs) of fidaxomicin versus vancomycin for the treatment of CDI published in Pubmed, Embase, Web of Science and the Cochrane library were searched. Two reviewers independently extracted the data. The primary outcome was the rates of clinical cure. The secondary endpoints were the rates of CDI recurrence in the 4 weeks period after the end of therapy and rates of global cure, adverse events. Meta-analysis was performed using the Mantle-Haenszel fixed effect method (FEM). Odds ratios (ORs) with 95% confidence intervals (95% CIs) were reported. The results indicated that two large randomized controlled trials were included in the meta-analysis. Clinical cure with fidaxomicin was similar to with vancomycin both in the modified intention to treat (OR = 1.17, 95% CI 0.82-1.66, P = 0.40) and in the per-protocol population (OR = 1.24, 95% CI 0.80-1.92, P = 0.34). There were no significant differences in the rates of clinical cure between fidaxomicin and vancomycin in the subgroups analyzed by age, patients’ status, and previous CDI, infection with B1 strain, severity baseline, and exposure to concomitant antibiotics. Recurrence of CDI was significantly less common among fidaxomicin-treated patients compared with vancomycin-treated patients both in the modified intention-to-treat population (OR = 0.47, 95% CI 0.34-0.65, P<0.00001) and in the per-protocol population (OR = 0.45, 95% CI 0.31-0.62, P<0.0001). Treatment with fidaxomicin compared with vancomycin was associated with significantly higher rates of global cure both in the modified intention-to-treat population (OR = 1.75, 95% CI 1.35–2.27, P<0.0001) and in the per-protocol population (OR = 1.86, 95% CI 1.40-2.47, P<0.0001). Our meta-analysis suggests that fidaxomicin is not superior to vancomycin in rates of clinical cure, while fidaxomicin significantly decreases the rates of CDI recurrence and significantly improves the rates of global cure compared with vancomycin. Thus, fidaxomicin is a promising candidate for treatment of the CDI, especially in decreasing the rates of CDI recurrence and improving the rates of global cure.

Determination of hyperoside in rat plasma after intravenous administration by UPLC-MS

Aimin Tan, Ping Lin^*, Fei Zhang

2013, 22(6): 516-520. DOI: 10.5246/jcps.2013.06.075

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Hyperoside is one of the major components of Hypericum perforatum L. and also present in many plant species such as Abelmoschus manihot (L.) Medik., Ribes nigrum L. and Rosa agrestis Savi (Rosaceae). Because hyperoside exhibits many biological activities, the pharmacokinetics profile of hyperoside needs to be studied for further elucidating its mechanism of action. A simple method for the determination of hyperoside in rat plasma was developed by using ultra-high performance liquid chromatography coupled with mass spectrometry (UPLC-MS). Only 50 µL plasma samples were required for sample preparation. The quantitative detection of hyperoside was accomplished by selected ion monitoring (SIM) in negative ion mode. Hyperoside was analyzed in less than 10 min. Good linearity was obtained (r²>0.999) and the intra- and inter-day precision of the method were lower than 15%. Lower limit of quantification (LLOQ) was 4 ng/mL for hyperoside in rat plasma. Our method showed advantage in the lower LLOQ compared with the reported method; furthermore, smaller amount of plasma was needed. The method was successfully applied for the pharmacokinetics study of hyperoside in rat after intravenous administration of hyperoside.

Simultaneous quantification of ten phenolic acids in Lonicerae Japonicae Flos by HPLC-DAD

Kuixia Chen, Yingtao Zhang^*, Xiuwei Yang*, Nan Wang, Wei Xu, Youbo Zhang, Yongqing Zhang

2013, 22(6): 521-526. DOI: 10.5246/jcps.2013.06.076

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A reverse-phase HPLC-DAD method was developed for simultaneous quantification of ten phenolic acids (caffeic acid, chlorogenic acid, neochlorogenic acid, 4-O-caffeoylquinic acid, 3,4-O-dicaffeoylquinic acid, 3,5-O-dicaffeoylquinic acid, 4,5-O-dicaffeoylquinic acid, 3,5-O-dicaffeoylquinic acid methyl ester, 3,4-O-dicaffeoylquinic acid methyl ester, and 4,5-O-dicaffeoylquinic acid methyl ester) in the dried flower buds of Lonicera japonica Thunb. (Lonicerae Japonicae Flos; LJF). An optimal sample preparation method was established as 30-min ultrasonication with 100 times 50% (v/w) ethanol aqueous solution based on the orthogonal test results. The chromatographic separation of the ten phenolic acids was achieved with an AQ-C18 column (4.6 mm×250 mm, 5 µm) and a gradient elution of acetonitrile, methanol and 0.1% formic acid aqueous solution within 55 min. All calibration curves showed good linearity (r²>0.999) within test ranges. The average recoveries were in the range of 98.57%-103.22% with RSD less than 3%. The method developed was accurate, sensitive and reproducible for determination of ten phenolic acids in LJF.

Sesquiterpenes from the aerial parts of Artemisia vestita Wall.

Shuaihua Tian, Helin Wei, Mingbo Zhao, Chen Zhang, Pengfei Tu^*

2013, 22(6): 527-530. DOI: 10.5246/jcps.2013.06.077

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A chemical investigation of the aerial parts of Artemisia vestita Wall. led to the isolation of 12 known sesquiterpenes, including 2 furan-containing sesquiterpenoids and 10 eudesmane sesquiterpene lactones. Their structures were identified as negunfurol (1), schensianol A (2), artemine (3), erivanin (4), 1,5-diepi-artemin (5), acetylartemin (6), naphtho[1,2-b]furan-2(3H)-one, 6-(acetyloxy)decahydro-9a-hydroxy-3,5a-dimethyl-9-methylene-(3S,3aS,5aS,6S,9aS,9bS) (7), naphtho[1,2-b]furan-2(3H)-one, 6-(acetyloxy)-3a,4,5,5a,6,7,8,9b-octahydro-8-hydroxy-3,5a,9-trimethyl- (3S,3aS,5aR,6S,8S,9bS) (8), isoerivanin (9), barrelierin (10), (11S)-1-oxoeudesm-4(14)-eno-13,6α-lactone (11), 1-epi-dehydroisoeranin (12), respectively. All of these compounds were isolated from Artemisia vestita for the first time, and compounds 1 and 2 were isolated from the genus Artemisia for the first time.

Specific oxidation of honokiol by Cunninghamella echinulata

Zhaohua Wang, Dewu Zhang, Zhengshun Wen, Lin Yang^*, Yeling Wang, Shanjun Wei, Jungui Dai^*

2013, 22(6): 531-534. DOI: 10.5246/jcps.2013.06.078

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Among 37 species of microbial strains, Cunninghamella echinulata AS 3.3400 were found to possess the ability to transform honokiol to (R)-magnolignan C (1) and (S)-magnolignan C (2) by regio-specific oxidation. Among them, 1 was a new compound. The structures of two compounds were determined by the analyses of CD, MS and NMR spectroscopic data.

Contents of Volume 22

Keywords Index of Volume 22

Author Index of Volume 22

Journal of Chinese Pharmaceutical Sciences

2013, 22(6): 535-546.

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Acknowledgements

Journal of Chinese Pharmaceutical Sciences

2013, 22(6): 547-547.

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The website of Journal of Chinese Pharmaceutical Sciences received “the 2nd excellent websites of Chinese University Journal”

Journal of Chinese Pharmaceutical Sciences

2013, 22(6): 548-548.

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Recently, the website of Journal of Chinese Pharmaceutical Sciences (JCPS) received “the 2^nd excellent websites of Chinese University Journal”. The journal’s website: http://www.jcps.ac.cn was fully functional in Sep. 2008, which further expands the accessibility of the journal. The published papers can be freely accessed on the website. In the mean time, some back issues has been added on the internet in PDF form. Our website also linked to the Chinese Pharmaceutical Association (CPA), Peking University Health Science Center, China National Knowledge Infrastructure (CNKI) and Wanfang database, improving the accessibility of the paper internationally.

Website: http://www.jcps.ac.cn

Journal of Chinese Pharmaceutical Sciences got financial support from “The International Influence of Chinese Science and Technology Journals Promotion Plan”

Journal of Chinese Pharmaceutical Sciences

2013, 22(6): 549-549.

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Journal of Chinese Pharmaceutical Sciences (JCPS) got financial support from “The International Influence of Chinese Science and Technology Journals Promotion Plan”, supported by China Association for Science and Technology (CAST), Ministry of Finance of the People’s Republic of China (MOF), Ministry of Education of the People’s Republic of China (MOE), General Administration of Press and Publication of the People's Republic of China (GAPP), etc. The plan will last 3 years, and the annual financial support is 5 million RMB yuan. JCPS has been indexed in the Core Journals of China’s science and technology field. At present, it has been included by Chemical Abstracts (CA), Ulrichsweb, Index of Copurnicus (IC), CABI, Scopus, China National Knowledge Infrastructure (CNKI), Chinese Science Citation Database (CSCD). In 2012, JCPS was awarded as “2012 International Influence Outstanding Academic Journals” and received “the 2^th Excellent Websites of Chinese University Journal” in 2013. In order to adapt to the new situation and meet the requirements of readers, JCPS will change bimonthly into a monthly journal from 2014. The project will provide a good opportunity for the internationalization of JCPS, and is better for Chinese innovative drug research and pharmaceutical industry.

General Information and Subscription

Journal of Chinese Pharmaceutical Sciences

2013, 22(6): 550-550.

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