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Table of Content

    27 January 2016, Volume 25 Issue 1
    Editor profile
    Review
    Effect of Rho-ROCK signaling pathway on pulmonary fibrosis
    Wenying Yu, Chenhuan Yu, Wei Dai, Jieyin Sun
    2016, 25(1):  3-11.  DOI: 10.5246/jcps.2016.01.001
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    Idiopathic pulmonary fibrosis (IPF) is characterized by progressive lung scarring, reduced median survival, poor prognosis and limited therapeutic options, leading to great need for new pharmacologic therapies. In recent years, researchers have found that Rho-ROCK signaling pathway may be a new drug target in the prevention of IPF. This article reviewed the role of Rho-ROCK pathway in pulmonary fibrosis and the application of ROCK inhibitors in experimental models of IPF. Multiple lines of evidence therefore indicated that ROCK inhibition has great potential to be a powerful therapeutic tool in the prevention and treatment of IPF in clinic. 

    Cancer prevention by traditional Chinese medicine and plant phytochemicals column
    Pharmacometrics of nutraceutical sulforaphane and its implications in prostate cancer prevention
    Sujit Nair, Ah-Ng Tony Kong
    2016, 25(1):  12-22.  DOI: 10.5246/jcps.2016.01.002
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    Sulforaphane (SFN), found in broccoli and other cruciferous vegetables, has a beneficial effect in chemoprevention of prostate cancer, whose incidence and associated mortality have gradually increased worldwide. There is great enthusiasm for bench-to-bedside development of SFN as a potent chemopreventive agent, possibly alone or as an adjunct to existing chemotherapyregimens, in the oncology care setting to reduce toxicity of chemotherapeutics and potentially enhance their cancer cell-kill efficacy. In this review, we appreciate existing knowledge on SFN using a pharmacometrics approach, which is fast becoming a gold standard in discovery research and validation of New Chemical Entities and New Biological Entities in pharmaceutical industry.We discuss the epistemology of SFN target engagement and quantitative systems pharmacology with due emphasis on mechanistic pharmacology, pharmacodynamics, pharmacogenomics and metabolism of SFN. In addition, we explore the quantitative freeway to SFN translational medicine by assessing the preclinical and clinical PK/metabolism aspects of SFN that form the cornerstone of SFN pharmacometric evaluation, as well as the promise of SFN in prostate cancer. Taken together, we share perspectives on the exciting developments in translational cancer chemoprevention, with emphasis on the pharmacometric aspects, of the nutraceuticalSFN which is currently in clinical trials, and suggest that the pharmacometric approach holds great promise in the SFN translational pharmacology paradigm for prostate cancer.

    Prenylated flavonoids from Glycyrrhiza uralensis as promising anti-cancer agents: a preliminary structure-activity study
    Shunan Tang, Wei Huang, Shuai Ji, Yongrui Wang, Daoyong Pei, Min Ye, Siwang Yu
    2016, 25(1):  23-29.  DOI: 10.5246/jcps.2016.01.003
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    Prenylated flavonoids are mainly distributed in Leguminosae and Moraceae plants, and they have been reported to possess various biological activities. Previously, we have reported a prenylated isoflavonoid, isoangustone A (IAA) from licorice (Glycyrrhiza uralensis), which induces apoptosis in colorectal cancer cells by disrupting mitochondrial functions. In the present study, we compared a group of flavonoids from licorice with IAA for their anti-proliferation activities and effects on intracellular signaling. The results indicated that the isoprenyl groups on the A and B rings, the hydroxyl groups at the ortho position of isoprenyl on A ring and the conjugated plane of C ring might contribute to the anti-cancer activity of prenylated flavonoids. Based on the above structure-activity relationship, we further identified four prenylated flavonoids with similar anti-cancer activities from licorice. Taken together, our present study established a preliminary structure-activity relationship of anti-cancer prenylated flavonoids, and our data provided important leading compounds from licorice, which deserved further research and development.

    Original articles
    Asymmetric total synthesis of 3-epi-naucleamide A
    Paruke Aibibula, Zhi Huang, Hongzheng Fu, Yanxing Jia
    2016, 25(1):  30-36.  DOI: 10.5246/jcps.2016.01.004
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    Attempts to collective synthesis of the monoterpene indole alkaloids, isolated from Nauclea species, were examined by using asymmetric conjugate addition with Evans’ chiral auxiliary as key step. However, only the H-15 and H-3 cis product 13 was obtained, which enabled us to achieve the asymmetric total synthesis of 3-epi-naucleamide A. The results indicate that this synthetic route can be applied in the synthesis of vincosamide.

    Insights into the neutral loss of 30 Da of Paeonia monoterpene glycosides in electrospray ionization tandem mass spectrometry and the rapid screening of monoterpene glycosides by LC/MS/MS
    Jing Cao, Xue Qiao, Shuai Ji, Wenjuan Miao, De-an Guo, Min Ye
    2016, 25(1):  37-45.  DOI: 10.5246/jcps.2016.01.005
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    Monoterpene glycosides are the major bioactive compounds of Paeonia lactiflora Pall (P. lactiflora). Characteristic neutral loss of 30 Da has been extensively reported for monoterpene glycosides in tandem mass spectrometry. However, little is known about mechanism of this fragmentation. The neutral loss of 30 Da was studied for eleven monoterpene glycosides (111) from P. lactiflora by ion trap mass spectrometry in this report. Compounds 15 with a hemiacetal structure could readily lose 30 Da at low collision energy of 30% in MS/MS by ion trap mass spectrometry. For compounds 611, neutral loss of 30 Da could also be observed at low abundance, but the collision energy had to be increased to 60%. In both cases, high-accuracy mass spectrometry assigned the 30 Da as CH2O. After careful analysis of the structures and mass spectra, we believe that the neutral loss of 30 Da in compounds 15 was due to cleavage of the hemiacetal structure, whereas it was ascribed to the cleavage of 5¢-hydroxymethyl group of the glucosyl residue in other monoterpene glycosides. Furthermore, the characteristic neutral loss of 30 Da at low collision energy was used to screen hemiacetals from crude extracts of P. lactiflora and related plant species. Significant differences among Paeonia species were observed by 30 Da neutral loss analysis.

    Chronic toxicity of both raw and processed Polygoni Multiflori Radix on rats
    Yanran He, Meizhen Song, Wangen Wang, Pei Lin, Yunfei Li, Wen Gu, Jie Yu, Ronghua Zhao
    2016, 25(1):  46-56.  DOI: 10.5246/jcps.2016.01.006
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    Recently, adverse effects of Polygoni Multiflori Radix (PMR) and Polygoni Multiflori Radix Praeparata(PMRP)have attracted intensive attention worldwide. These adverse effects most occurred in caseswith high dose of prolonged medication course.Liver is usually the target organ of these adverse effects. In the present research,we performedin vivo chronic toxicity study and aimed to evaluate relationships between major constituents of water extractions and total anthraquinone of PMR and PMRP and chronic toxicity.SD rats of both sexes were given water extractions as well as total anthraquinone of PMR and PMRP for 12 weeks.We evaluated basic biochemical indexes, conducted microscopic observations of main organs and assessed early indicators of liver and renal fibrosis. Simvastatin, with hypertriglyceridemia and hypercholesterolemia as its main therapeutic areas, was investigated in our study. Component-toxicity relationships were also discussed.Five male rats died in our study, while all female rats survived, suggesting that some gender differences might be involved. Body weightwas significantly changed, and basic biochemical indexes were sporadically occurred during the research. Pathological examinations on liver and kidney showed slight alternations after 12 weeks without dose-dependent relationship. Increase in serum laminin (LN) was observed in almost all male rats, indicating that the risks of liver or kidney fibrosis still existed, especially for males, although no fibrosis was found in the pathological examination of liver and kidney.No major and severe adverse effects were observed after 12 weeks of administration of PMR and PMRP. Regular safety monitoring is still necessary during medication in order to prevent possible risks.

    Blockage of p53 reduces acute alcohol-induced neuronal apoptosis
    Xiaojin Yan, Yushuang Chai, Fan Lei, Dongming Xing, Lijun Du
    2016, 25(1):  57-65.  DOI: 10.5246/jcps.2016.01.007
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    Dysfunction and apoptosis of neurons triggered by various stimulations mainly contribute to neurodegenerative diseases.Gradually appeared reports have indicated that stimulations can initiate activation of aberrant cell cycle factors in neurons, leading to abnormal cell behavior and apoptosis finally. In our study, apoptosis induced by activation of cell cycle factors was investigated using mice and PC12 cells as acute alcohol exposure models in vivo and in vitro, respectively. Moreover, p53 inhibitor and CDK4 inhibitor were applied in alcohol-treated PC12 cells to define the essential roles of p53, cyclin D1 and CDK4 in caspase-3 apoptotic pathway upon acute alcohol exposure. The data showed that acute excessive alcohol exposure up-regulated the expressions of p53, CDK4 and cyclin D1, and it also triggered apoptosis. However, chronic consumption of low content of alcohol did not cause neuronal apoptosis. Inhibition of p53 weakened the activation of caspase-3 and attenuated alcohol-induced apoptosis in PC12 cells, whereas blockage of cyclin D1 and CDK4 did not have such an effect. Blockage of p53/caspase-3 pathway would give cells time to metabolize alcohol and repair alcohol-caused damage. Taken together, neuronal apoptosis triggered by acute excessive alcohol exposure was correlated to activation of the p53/caspase-3 signaling, and blockage of p53 would be a possible way to suppress acute alcohol exposure-induced apoptosis.

    Evaluation on telbivudine-associated rhabdomyolysis
    Zhanmiao Yi, Shidie Tang, Fang Liu, Suodi Zhai, Ligong Jiao
    2016, 25(1):  66-72.  DOI: 10.5246/jcps.2016.01.008
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    To investigate clinical characteristics and related factors of telbivudine-associated rhabdomyolysis (RM), we searched domestic and foreign medical literature databases as well as Beijing Adverse Drug Reaction Monitoring Database. Cases of telbivudine-associated RM were collected. General information of patients and information of medications were extracted. Onset of adverse drug reactions (ADRs), clinical manifestations, treatments and outcomes were investigated and analyzed. After reviewing226 literatures and 71 reports, a total of 22 RM cases were collected. All the cases were male patients with an average age of (34.5±11.2) years, and all these patients had chronic hepatitis B and received telbivudine 600 mg/day. The occurrence time of RM varied. One case occurred within 5 months (4.5%), 11 cases occurred within 6 to 10 months (50.0%), 8 cases occurred within 11 to 15 months (31.8%), and 3 cases occurred after 15 months (13.6%). Clinical manifestations were mostly nausea, vomiting, palpitations, weakness and edema of the lower extremities. After the telbivudine treatment was discontinued and symptomatic treatments were provided, 12 patients were clinically improved, 4 patients were physically impaired, 2 patients showed unknow results, and 4 deaths were reported. However, age (P = 0.61), duration of medication (P = 0.54) and CK value (P = 0.07) were not statisticallyassociated with death. Clinicians are advised to monitor clinical manifestations in patients receiving telbivudine. Monitoring on serum creatinine level is suggested if necessary. Telbivudine should be promptly discontinued, and symptomatic treatment should be given when ADRs occur.

    Short communication
    Management of pharmaceutical sales representatives: A literature review
    Swapnil Undale, Dr. Milind Pande
    2016, 25(1):  73-78.  DOI: 10.5246/jcps.2016.01.009
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    This paper reports literature review in the field of pharmaceutical marketing emphasizing problems faced by medical representatives. India after globalization and being the second highest populated country has emerged as major pharmaceutical market in the world. Pharmaceutical marketing in India is highly relied on personal relationship between medical representatives and doctors. In the last decade, many foreign companies have entered in Indian market. This has posed highly competitive and challenging work environment for medical representatives. Therefore, it is indispensable to study the challenges faced by medical representatives in this dynamic environment.

    Others
    Information for Authors
    Journal of Chinese Pharmaceutical Sciences
    2016, 25(1):  79-88. 
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    Journal of Chinese Pharmaceutical Sciences Rated “The Excellent International Impact Academic Journals of China, 2015”
    Journal of Chinese Pharmaceutical Sciences
    2016, 25(1):  89-89. 
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    The Result of “2015 Excellent Articles of Journal of Chinese Pharmaceutical Sciences” is Announced
    Journal of Chinese Pharmaceutical Sciences
    2016, 25(1):  90-90. 
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    Atthe energetic support of scholars and relevant agencies, the result of 2015 Excellent Paper of Journal of Chinese Pharmaceutical Sciences is announced.
    The 2015 Excellent Paper award is under the strict rule of editorial office of Journal of Chinese Pharmaceutical Sciences. Firstly,weidentified 16 candidate from 104 original paper published in our journal 2015. Then, editorial office invited more than 60 experts as evaluation experts. The judges voted to choose 10 Excellent Paper from the 16 candidate. The titles and authors of 2015 Excellent Paper are as follows.