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Table of Content

    29 March 2016, Volume 25 Issue 3
    Review
    Cerbera are coastal trees with promising anticancer properties but lethal toxicity: A short review
    Eric Wei Chiang Chan, Siu Kuin Wong, Hung Tuck Chan, Shigeyuki Baba, Mio Kezuka
    2016, 25(3):  161-169.  DOI: 10.5246/jcps.2016.03.019
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    In this short review, the current knowledge on the chemical constituents and anticancer properties of Cerbera odollam and Cerbera manghas is updated with some description of their botany and uses. Although these two closely-related coastal tree species have overlapping geographical distribution, they can be distinguished by the eye colour of flowers and the shape of fruits. Chemical constituents of C.odollam and C.manghas include lignans, iridoids, terpenoids, cardiac glycosides (cardenolides), flavonoids, phenolic acids and steroids. Cardiac glycosides of cerberin, dehydrocerberin, neriifolin, tanghinin, deacetyltanghinin and tanghinigenin possess promising anticancer properties with apoptotic activities. However, these cardiac glycosides are also cardiotoxic. Fatal cases of suicides by ingesting Cerbera fruits or seeds have been reported in India and Sri Lanka. In two suicide cases, one in Taiwan and another in the United States, the patients recovered completely. In New Caledonia, four death-threatening cases of poisoning (two were fatal) occurred through consuming toxic coconut crabs. Taken together, both C. odollam and C. manghas are endowed with cardiac glycosides, which have useful pharmacological properties but lethal toxicity.

    Cancer prevention by traditional Chinese medicine and plant phytochemicals column
    Mechanisms of prostate carcinogenesis and its prevention by a γ-tocopherol-rich mixture of tocopherols in TRAMP mice
    Ying Huang, Zhengyuan Su, Tienyuan Wu, Constance Lay-Lay Saw, Ah-Ng Tony Kong
    2016, 25(3):  170-177.  DOI: 10.5246/jcps.2016.03.020
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    Tocopherols belong to a subgroup of the vitamin E family. Dietary feeding of a γ-tocopherol-rich mixture of tocopherols-TmT) inhibits prostate tumorigenesis in TRAMP mice. In this study, we aimed to investigate mechanisms of prostate carcinogenesis in TRAMP mice by identifying differentially expressed pathways and effects of γ-TmT on these pathways. Eight-week-old TRAMP and age-matched C57BL/6 mice were administered either 600 mg/kg of γ-TmT or a control vehicle via oral gavage. Twelve hours after dosing, prostate tissues were collected for RNA extraction. Whole genome mouse microarrays were used to examine gene expression profiles. The expression of the selected genes were validated using quantitative PCR. Thousands of genes and various pathways were altered in the prostates of TRAMP mice. Compared to C57BL/6 mice, TRAMP mice exhibited enhanced proliferation, suppressed expression of antioxidant and phase II detoxification enzymes, and metabolic reprogramming in the prostate. γ-TmT differentially regulated the gene expression profiles of TRAMP and C57BL/6 mice, with only a small percentage of genes overlapping. γ-TmT inhibited genes involved in proliferation and glucose metabolism and induced several antioxidant/phase II detoxification genes in TRAMP mice. γ-TmT modulates multiple aberrant pathways in the prostate of TRAMP mice, which might represent important mechanisms for prostate cancer prevention.

    Original articles
    Formononetin ameliorates DSS-induced ulcerative colitis in mice through induction of Nrf2 in colons
    Qian Yang, Gang Chen, Yang Yang, Xueting Cai, Zhonghua Pang, Chunping Hu, Shuangquan Zhang, Peng Cao
    2016, 25(3):  178-188.  DOI: 10.5246/jcps.2016.03.021
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    Isoflavone formononetin (FN) is a main active component of red clover (Trifolium pratense L.), a medicinal plant possessing antitumorigenic and antioxidant properties. In the present study, we aimed to examine the effect of FN on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. The results showed that FN (25, 50 mg/kg) markedly attenuated the loss of body weight, the disease activity index (DAI), shortening of colon length and tissue injury induced by DSS treatment. In addition, the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2) were also significantlyreduced in FN treatment group compared with the DSS group. Moreover, several representative oxidative stress parameters in colorectum, including superoxide dismutase (SOD), methane dicarboxylic aldehyde (MDA), myeloperoxidase (MPO) and 8-oxoguanine, were markedly ameliorated. In this study, we also found that the expression of Nrf2 was increased by FN treatment.However, symptoms of UC were not ameliorated in Nrf2 knockout mice. Taken together, FN could prevent the development of UC through activating of Nrf2 axis, and the protective effect was Nrf2 dependent. Our results demonstrated that FN might be a potential therapeutic agent in the treatment of UC.

    Establishment and application of the screening model of the Mycobacterium tuberculosis β-lactamase BlaC inhibitors
    Yishuang Liu, Jiayin Zheng, Shuchao Huang, Yan Guan, Chunling Xiao
    2016, 25(3):  189-195.  DOI: 10.5246/jcps.2016.03.022
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    With the continuous emergence and rapid spread of multidrug-resistant and extensively-drug-resistant Mycobacterium tuberculosis strains, it is imperative to develop novel therapies against this bacterium. The intrinsic β-lactam resistance ofM. tuberculosis is primarily due to the production of an Ambler class-A β-lactamase BlaC, which limits the application of β-lactam antibiotics in the treatment of tuberculosis. Therefore, the inhibitors of BlaC could be novel anti-tuberculosis drug synergistic agents to recover the sensibility of M. Tuberculosis to the β-lactam antibiotics. In the present study, BlaC of M. tuberculosis was expressed and purified to establish a screening model of the BlaC inhibitors. The screening conditions were determined, and the screening model was evaluated to fit for the high throughput screening. A total of 22 BlaC inhibitors were screened out from 26 400 compound samples with a positive rate of 0.083%. Taken together, our findings lay the foundation for the discovery of novel anti-tuberculosis drug synergistic agents in clinic.

    Interaction of isoliquiritigenin with bovine serum albumin studied by fluorescence quenching method
    Bo Han, Fei Long, Wei Yu, Wen Chen, Xinchun Wang, Gang Guo, Liangxue Zhou
    2016, 25(3):  196-200.  DOI: 10.5246/jcps.2016.03.023
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    Interaction of ioliquiritigenin (ISL), which is the main active component of a commonly used traditional Chinese medicine (TCM) Glycyrrhiza uralensis Fisch. with bovine serum albumin (BSA) has been investigated. The quenching mechanism of fluorescence of bovine serum albumin by ISL was discussed. The binding sites number n and apparent binding constant K were measured by fluorescence quenching method. The thermodynamic parameters ΔH0, ΔG0, ΔS0 at different temperatures were calculated. The distance r between donor (bovine serum albumin) and acceptor (ISL) was obtained according to Förster theory of non-radiation energy transfer. The results of synchronous fluorescence spectra and UV-vis absorption spectra show that the conformation of bovine serum albumin has been changed.

    Chemical constituents from Murraya tetramera Huang
    Ying Zhou, Wenguang Wang, Pengfei Tu, Yong Jiang
    2016, 25(3):  201-205.  DOI: 10.5246/jcps.2016.03.024
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    The aim of this study is to perform a phytochemical investigation of the aerial parts of Murraya tetramera Huang. Nine compounds wereisolated by silica gel and Sephadex LH-20 chromatography, together with preparative TLC and HPLC methods. By analysis of the MS and NMR spectroscopic data and comparison with those in literature, these nine compounds were identified as 3,3'-[oxybis(methylene)]bis(9-methoxy-9H-carbazole) (1), murrastifoline B (2), murrayaquinone A(3), 2,4-dimethoxyphenol (4), 1,2-dimethoxy-4-nitrobenzene (5), 3-methylanisole (6), (–)-syringaresinol-4-O-β-D-glucopyranoside (7), β-sitosterol (8), and octadecanyl-3-methoxy-4-hydroxylbenzeneacrylate (9), respectively. Among them, compounds 46 and 9 were described from the genus Murraya for the first time, and compounds 29were isolated from M. tetramera for the first time.

    Clinical pharmacy column
    Incretin-based therapies for type 2 diabetes with nonalcoholic fatty liver disease: a systematic review and meta-analysis
    Qin Hu, Hulin Tang, Hong Shao
    2016, 25(3):  206-214.  DOI: 10.5246/jcps.2016.03.025
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    We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the effectiveness and safety of incretin-based therapies (IBTs) for the treatment of type 2 diabetes (T2DM) with nonalcoholic fatty liver disease (NAFLD). Electronic databases such as the Cochrane library, EMbase, PubMed, and three Chinese databases were searched for RCTs that compared IBTs with other treatments or placebo for T2DM with NAFLD. Two reviewers independently assessed the risk of bias, extracted, and analyzed the data. A meta-analysis was performed using Revman 5.2. Publication bias was evaluated. Seven RCTs involving 532 patients were ultimately included. The results of meta-analysis (random-effects model)revealed that IBTs had a significant reduction in serum ALT (WMD –12.30, 95% CI –17.53~–7.06) and BMI (WMD –2.64, 95% CI –4.35~–0.94). However, there was no significant difference in other outcomes including HbA1c, AST, TC, TG and HOMA-RA. IBTs were well tolerated by patients but the evidence was limited. The significant decrease in hepatic biochemical markers following treatment with IBTs, as well as improvements in BMI, suggested that IBTs may be an effective option for T2DM with NAFLD.

    Efficacy and safety of telavancin: a systematic review and meta-analysis
    Yue Dong, Ming Zhao, Xin Hu
    2016, 25(3):  215-223.  DOI: 10.5246/jcps.2016.03.026
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    The emergence and rapid spread of multidrug-resistant gram-positive bacteria has become a vital and serious medical problem. A literature search was conducted in PubMed, EMBASE, and Elsevier databases to identify relevant publications. To calculate the risk ratios (RRs) with 95% confidential intervals (CIs), a fixed- or random-effects model was applied based on the heterogeneity across studies. Five studies containing seven RCTs were included in this meta-analysis. Regarding cSSTIs, HAP, SAB, there was no statistically significant difference in the rate of clinical cure between telavancin and vancomycin or standard therapy in intention-to-treat population (ITT) (RR 1.01, 95% CI 0.97–1.05, P = 0.72; FEM) and clinically evaluable population (CE) (RR 1.01, 95% CI 0.98–1.04, P = 0.41; FEM). However, telavancin was more effective than vancomycin or standard therapy in MRSA eradication rate (RR 1.08, 95% CI 1.02–1.14, P = 0.009; FEM). Regarding the safety profile, no statistically significant differences were found in all-cause mortality (9.0% vs. 8.4%; RR 1.07, 95% CI 0.88–1.31, P = 0.49; FEM) and overall adverse events (77.0% vs. 72.3%; RR 1.08, 95% CI 0.98–1.20, P = 0.12; FEM) between telavancin and vancomycin or standard therapy. Pooled data from cSSTIs, HAP and SAB studies on telavancin indicated higher rates of adverse-event related withdrawals (7.7% vs. 5.4%; RR 1.43, 95% CI 1.12–1.83, P = 0.05; FEM) and creatinine elevation (10.0% vs. 5.1%; RR 1.95, 95% CI 1.53–2.48, P<0.00001; FEM)than vancomycin or standard therapy.Telavancin and vancomycin or standard therapy are equally effective for the treatment of cSSTIs, HAP and SAB, and telavancin might be an option for the treatment of difficult-to-treat serious infections caused by MRSA. However, telavancin is associated a higher incidence of creatinine elevation and adverse-event related withdrawals.

    Short communication
    Inhibition of protein tyrosine phosphatase 1B by triterpenes isolated from Potentilla discolor Bge
    Zhendong Tuo, Na Li, Jialin Li, Shizhou Qi, Banban Li, Le Zhang, Long Cui
    2016, 25(3):  224-227.  DOI: 10.5246/jcps.2016.03.027
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    Seven oleanene triterpenes were isolated from the roots of Potentilla discolor Bge and their structures were identified as3-oxoolean-12-en-27-oic acid (1), gypsogenic acid (2), 3α-hydroxyolean-12-en-27-oic acid (3), 3β-hydroxyolean-12-en-27-oic acid (4), aceriphyllic acid A (5), aceriphyllic acid A methyl ester (6), and oleanolic acid (7). Compounds 17 inhibited protein tyrosine phosphatase 1B (PTP1B) activity, with IC50 values ranging from (7.5±0.5) to (22.7±0.5) μmol/L. Among the isolates, compounds 1, 2, 3 and 7 from thePotentilla discolor Bge were found to exhibit selective PTP1B inhibitory activity.

    Others
    Profs. Pengfei Tu, Xiuwei Yang, and Wanliang Lv from School of Pharmaceutical Sciences, Peking University were elected into the “2015 List of the Highly Cited Scholars in China”
    Wenguang Wang
    2016, 25(3):  228-229. 
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    In January 26, Elsevier, an academic publishing company that publishes medical and scientific literature, released the “2015 List of the Highly Cited Scholars in China” after a scientific evaluation of Chinese researchers’ influence on the world. The data of the list is from Scopus, the largest abstract and citation database of peer-reviewed literature, including scientific journals, books, and conference proceedings. 1744 most influential Chinese scientists in various academic fields including social science, physics, chemistry, mathematics, economics, etc. were elected into the list. Profs. Pengfei Tu, Xiuwei Yang, and Wanliang Lv from School of Pharmaceutical Sciences, Peking University were included in the list again after 2014.

     
    Prof. Pengfei Tu’s group won second prize of 2015th National Science and Technology Progress Award
    Yuelin Song
    2016, 25(3):  230-232. 
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    In January 8th 2016, the 2015th National Science and Technology Awards Conference was held by the CPC Central Committee and the State Council in the Great Hall. Party and state leaders, Jinping Xi, Keqiang Li, Yunshan Liu, Gaoli Zhang, etc attended the meeting and presented the awards to the winners. The project namely “Effective ingredients-based new technologies for quality control of traditional Chinese medicines (TCMs) and its application in crude drugs and Honghua injection” performed by Prof. Pengfei Tu’s group from School of Pharmaceutical Sciences, Peking University, won the second prize of National Science and Technology Progress Award. Principal investigators for this project include Pengfei Tu, Yong Jiang, Jun Li, Bingxiang Zhao, Shenghua Liu, Ying Tan, Shepo Shi, Yaning Zhu, Mingbo Zhao, and Yuelin Song, and the principle units included Peking University, Ya’an Sanjiu Pharmaceutical Co., Ltd. and Jinpai Co., Ltd. Profs. Tu and Jiang, as well as Dr. Zhao were invited as delegates to attend the meeting. As the first investigator, Prof. Tu received an interview from President Jinping Xi and some other party and state leaders, and all of them posed for a group photo.