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Table of Content

    30 May 2016, Volume 25 Issue 5
    Reviews
    Rhein: a novel potential antitumor drug
    Lu Yu, Guodong Yao, Weicheng Ma
    2016, 25(5):  321-328.  DOI: 10.5246/jcps.2016.05.036
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    Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid) is an anthraquinone compound enriched in the rhizome of rhubarb (Rheum palmatum or Rheum tanguticum Maxim), a traditional Chinese medicine herb. Natural product compounds are a source of novel therapeutic agents. Rhein has been initially identified as an anti-inflammatory and anti-oxidant agent. Recent studies indicate that rhein may also have an antitumor effect. However, the molecular mechanisms are still unclear. This review aims to summarize the research of rhein to better understand the anti-tumor activities by targeting cell cycle arrest, apoptosis, invasion, and metastasis of cancer cells. Meanwhile, we also intend to give an overview of the mechanisms identified so far. The breakthrough findings may shed light on using rhein as a targeted-cancer therapy.

    Research progress on the functions of vitamins in body
    Lingyan Gao, Xiao Ma, Xiao Liu
    2016, 25(5):  329-341.  DOI: 10.5246/jcps.2016.05.037
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    Vitamins are natural materials essential for maintaining the normal physical function of the live cells. It has been reportedthat 13 vitamins are needed in our body, included vitamin A, B vitamins (thiamine, riboflavin, niacin, pantothenic acid, pyridoxine, biotin, folic acid and cobalamin), vitamin C, vitamin D, vitamin E and vitamin K. Nowadays, the functions of vitamins have been extensively investigated. The objective of this paper is to summarize the new functions of vitamins, aiming to provide suggestions on the usage of various vitamins in clinical application.

    Original articles
    A liquid chromatography-tandem mass spectrometric method for the determination of axitinib in nude mouse plasma: development, validation and application to a pharmacokinetic study
    Yuanheng Ma, Jian Li, Qinghong Su, Wenjun Chen, Wei Lu, Tianyan Zhou
    2016, 25(5):  342-350.  DOI: 10.5246/jcps.2016.05.038
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    In the present study, a simple, rapid, and sensitive liquid chromatography-tandem mass spectrometric method for the determination of axitinib in nude mouse plasma was developed, validated, and applied to a pharmacokinetic study. Plasma samples were pre-treated by protein precipitation with acetonitrile spiked with erlotinib as an internal standard. The chromatographic separation was accomplished by using a reversed phase C18 column (50 mm×2 mm, 5 μm) with a simple mobile phase system composed of methanol and water (60:40, v/v) at an isocratic flow rate of 0.4 mL/min. The analyte was detected by a triple-quadrupole tandem mass spectrometer via electrospray ionization and multiple reaction monitoring was employed to select both axitinib and erlotinib in the positive ion mode. The calibration curves were linear (r>0.99) ranging from 1 to 1000 ng/mL, and the lowest level of this range was the lower limit of quantification. The intra­ and inter­day precision were 7.7%-12.0%, and the accuracies ranged from 88.6% to 110.4%. This method was successfully applied to a preclinical pharmacokinetic study on female nu/nu nude mice administrated with a single oral dose of axitinib at 120 mg/kg, and the pharmacokinetics was characterized by a one-compartment model with first-order absorption.

    The reversal effects of piperine and (R)-(+)-citronellal on multidrug resistant breast cancer cells
    Yi Zhou, Ting Wang, Jiajia Zhao, Ling Wang, Xuehua Jiang
    2016, 25(5):  351-356.  DOI: 10.5246/jcps.2016.05.039
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    Multidrug resistance (MDR) in tumor cells can reduce the efficacy of chemotherapy. Overexpression of transporters is an important mechanism for MDR. P-glycoprotein (P-gp) is an ATP-binding cassette transporter frequently expressed in multidrugresistant tumor cells, inducing MDR. To reverse P-gp dependent MDR, anticancer drugs can be administered with P-gp inhibitors. Piperine and (R)-(+)-citronellal both are P-gp inhibitors from dietary sources. In the present study, we aimed to evaluate the MDR reversal effects of piperine and (R)-(+)-citronellal in multidrug resistant MCF-7/DOX cells. The results of cytotoxicity studies indicated that piperine and (R)-(+)-citronellal both could abate the resistance of MCF-7/DOX after 72-h incubation. After 72-h incubation, piperine could dose-dependently down-regulate the MDR1 expression at the mRNA level, while (R)-(+)-citronellal had no effect on the MDR1 expression. Therefore, piperine and (R)-(+)-citronellal both could reverse MDR in MCF-7/DOX cells, and the reversal effect of piperine was related to dose-dependent down-regulation of the MDR1 expression at the mRNA level.

    Neuroprotective effects of xanthone extract from Swertia punicea Hemsl against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinson’s disease
    Yongfei Guo, Chen Wang, Wan Li, Ke Zhang, Hui Lei, Yi Sun, Xiaoping Pu, Xin Zhao
    2016, 25(5):  357-365.  DOI: 10.5246/jcps.2016.05.040
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    As a widely used traditional Chinese medicine (TCM), Swertia punicea Hemsl has exhibited effects on anti-hepatitis B virus (HBV), liver protection, hypoglycemic activity and cholecystitis. In this study, we confirmed that xanthone extract from Swertia punicea Hemsl (XSPH) improved the motor deficit, increased the levels of striatal dopamine (DA) and homovanilic acid (HVA), and alleviated the loss of tyrosine hydroxylase (TH)-positive neurons located in substantia nigra pars compacta (SNpc) in MPTP-induced mouse model of Parkinson’s disease (PD). In conclusion, the present results indicated that XSPH offered neuroprotective effects against the neurotoxicity of MPTP and it might be a potential treatment for PD.

    Albiflorin attenuates inflammatory injury by regulating the TLR4 signaling pathway and its negative regulating factor Tollip in experimental models of ulcerative colitis
    Xinhua Fang, Xin Wu, Xuemei Zhu, Hao Cai, Gang Cao
    2016, 25(5):  366-372.  DOI: 10.5246/jcps.2016.05.041
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    Albiflorin (AF) is the main active component extracted from Paeoniae Radix Alba. This study investigated the efficacyof AF in attenuating inflammatory injury by regulating the TLR4 signaling pathway and its negative regulating factor Tollip in an experimental ulcerative colitis (UC) model. We administrated trinitrobenzene sulfonic acid for 21 d to induce UC in rats. The efficacy of AF in attenuating UC was assessed using various biochemical markers, such as tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-10 (IL-10), 5-hydroxytryptamine (5-HT), and tissue myeloperoxidase (MPO), along with histopathological studies on toll-like receptor-4 (TLR-4) signaling pathway and its negative regulating factor Tollip. The results showed that AF can significantly downregulate the levels of TNF-α, IL-1, IL-10, and 5-HT. AF decreased the activation of TLR4, MyD88, and NF-κB p65 protein expression by increasing Tollip expression. AF can relieve symptoms of UC by suppressing the activation of the TLR4 signaling pathway and upregulating its negative regulating factor Tollip. Therefore, AF may be a potential natural product for treating UC.

    Optimization of ultrasound assisted extraction of six major compounds from Cimicifugae Rhizome
    Wei Chen, Qin Yuan, Junping Cheng, Huinan Ge, Guorong Jiang, Rong Chen
    2016, 25(5):  373-379.  DOI: 10.5246/jcps.2016.05.042
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    Cimicifugae Rhizome (RC) is one of many commonly used traditional Chinese medicines. This study used Box-Behnken Design (BBD), a widely used form of response surface methodology (RSM), to optimize the conditions of the ultrasound-assisted extraction (UAE) for the extraction of phenolic compounds from CimicifugaeRhizome. The influence of three independent variables,including ethanol concentration (%), extraction time (min) and solvent-to-material ratio (mL/g), on the extraction yields of phenolic compounds were examined. The results demonstrated that the optimal ultrasound-assisted extraction (UAE) conditions were as follows: ethanol concentration of 68%, an extraction time of 19 min, and solvent-to-material ratio of 30 mL/g for the extraction of caffeic acid, cimicifugoside, ferulic acid, isoferulicacid, cimifugin, 4'-O-β-glucopyranosyl-5-O-methylvisamminol. These results demonstrated the suitability of UAE for the extraction of phenolic compounds from CimicifugaeRhizome.

    An UPLC-MS/MS application to investigate the chemical composition of the ethanol extract from Anoectochilus chapaensis and its hypoglycemic activity in insulin-resistant HepG2 cells
    Cai Jinyan, Ni Jun, Zhao Lin
    2016, 25(5):  380-386.  DOI: 10.5246/jcps.2016.05.043
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    Anoectochilus chapaensis Gagnep. (Orchidaceae) was named as the “king of medicine” because of its excellent efficacy for the treatment of diabetes. However, the bioactive constituents are unknown. An ethanol extract from A. chapaensis showed significant stimulating effect on glucose consumption in HepG2 cells. The chemical composition was investigated by UPLC-MS/MS in negative electrospray ionization (ESI) mode, and 63 compounds including flavonoids, triterpenoids, and aliphatic acids were tentatively identified by accurate mass and characteristic fragments. Moreover, the method of hypoglycemic screening with insulinresistant HepG2 cells and UPLC-MS/MS might be potentially useful in rapid and efficient characterization and primary prediction of natural products prior to traditional isolation.

    Meta-analysis of the clinical efficacy and safety of oxycodone and morphine in cancer pain treatment
    Xin Rao, Changlian Wang, Xiongwei Xu, Pinfang Huang, Hang Wang, Lu Lin
    2016, 25(5):  387-394.  DOI: 10.5246/jcps.2016.05.044
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    In the present study, the efficacy and safety of oxycodone and morphine in the treatment of cancer pain were compared in a meta-analysis with the goal of providing a reference for drug selection in clinical practice. Electronic literature databases were searched for articles published through February 2015, including PubMed, MEDLINE, the Cochrane library, and Embase; and the China National Knowledge Internet, VIP Databases and Wanfang Databases for studies published in Chinese. Only randomized controlled trials were selected. The primary outcome measures were efficacy and the incidence of adverse drug reactions (ADRs). Data were extracted from the studies by two independent reviewers. A total of 15 studies containing 1338 patients were included in the analysis. The studies were divided into two subgroups according to different scoring methods. The pain relief efficacies of oxycodone and morphine were rated by the numerical rating scale (NRS) (risk ratio [RR]: 1.04; 95% confidence interval [CI]: 0.97–1.11). Others were rated by the visual analog scale (VAS) (RR: 1.03; 95% CI: 0.97–1.10). Five studies showed that pain intensity scores did notsignificantly differ between oxycodone and morphine treatments (standard mean difference [SMD] = 0.16, 95% CI: –0.01~0.33, P = 0.06). Regarding ADRs, the incidence of constipation was lower in the oxycodone group (RR: 0.70; 95% CI: 0.58–0.85). No statistical difference was observed among other ADRs. The efficacies of oxycodone and morphine were similar in treating cancer pain. However, the incidence of constipation was lower in patients treated with oxycodone.