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Table of Content

    28 February 2019, Volume 28 Issue 2
    Review
    Phenolic constituents from the root bark of Morus alba with emphasis on morusin and its anti-cancer properties
    Eric Wei Chiang Chan, Siu Kuin Wong, Tomomi Inoue, Hung Tuck Chan
    2019, 28(2):  75-87.  DOI: 10.5246/jcps.2019.02.008
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    The root bark of Morus alba L. or white mulberry is widely used as traditional medicine in China, Japan and Korea. Major classes and types of phenolic compounds isolated from the root bark are flavonoids (kuwanons, morusin, cyclomorusin and sanggenons), benzofurans (moracins and mulberrofurans), and stilbenoids (mulberrosides). Some of the flavonoids and benzofurans are products of Diel-Alder type adducts. Other classes of compounds include triterpenes, phenolic acids and coumarins. Morusin, a prenylated flavonoid, was first isolated from the root bark of M. alba, and later from the leaf, stem bark and twig of the plant. The potent anti-cancer properties of morusin have attracted much attention with research on-going and new findings being published. The compound inhibits angiogenesis, tumour progression and tumour migration, and triggers apoptosis, cell cycle arrest and autophagy in colorectal, cervical, prostate, breast, hepatoma, pancreatic, glioblastoma, gastric, ovarian and lung cancer cell lines. The anti-cancer activities of morusin are executed via various molecular targets and signalling pathways. It is anticipated that on-going in vitro studies will progress gradually to in vivo studies using animal models before efforts towards drug development can be initiated for clinical trials.
    Original articles
    Xiao-Xu-Ming decoction extract alleviates LPS-induced neuroinflammation associated with down-regulating TLR4/MyD88 signaling pathway in vitro and in vivo
    Xiao Cheng, Huan Yang, Yinglin Yang, Weihan Li, Man Liu, Yuehua Wang, Guanhua Du
    2019, 28(2):  88-99.  DOI: 10.5246/jcps.2019.02.009
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    In the present study, we aimed to investigate the effects of Xiao-Xu-Ming decoction extract (XXM) on lipopolysaccaride (LPS)-induced neuroinflammation invitro and invivo. Invitro, the microglia BV2 cells were treated with 200 ng/mL LPS for 24 h to induce inflammatory responses. Invivo, mice were treated with 5 mg/kg LPS to induce inflammatory responses. The NO level was determined by Griess Reagents. The levels of IL-1β, IL-6, TNF-α and MCP-1 were determined by ELISA. The expressions of Iba-1, TLR4 and MyD88 at the protein levels were determined by Western blotting analysis. The mRNA levels of TLR4 and MyD88 were determined by real-time PCR. Invitro, XXMsignificantly reduced the levels of various pro-inflammatory factors, including NO, IL-1β, IL-6 and TNF-α, induced by LPS in the supernatant of BV2 cells and suppressedexpressions of inflammatory proteins TLR4 and MyD88 induced by LPS in BV2 cells. Invivo, XXM significantly inhibited microglia activation, attenuated LPS-induced inflammatory factors and chemokine production, such as IL-1β, IL-6, TNF-α and MCP-1, andinhibited the expressions of inflammatory proteins including TLR4 and MyD88, in the cortex of LPS-induced mice. Our findings suggested that XXM could attenuate LPS-induced neuroinflammation via down-regulating TLR4/MyD88 signaling pathway.
    Curcumin inhibits inflammatory cytokine transcription via the apoptosis pathway in THP-1 cells
    Jianwei Gao, Feng Ye
    2019, 28(2):  100-113.  DOI: 10.5246/jcps.2019.02.010
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    To investigate the anti-inflammatory mechanism of curcumin in THP-1 cells induced by LPS, the effect of curcumin on inflammatory cytokine mRNA expression was assessed by Real-time PCR. Covalent post-translational modification profiles were determined by a PathScan® Kit. Western blotting analysis verified the PathScan results and the effects of curcumin on nucleus-relatedprotein changes. Annexin V-FITC and PI staining was used to detect early cellular apoptosis by flow cytometry. Anti-inflammatory effects of curcumin were mediated by reducing the levels of IL-1β, IL-6, TNF-α and ICAM-1 mRNA. However, PathScan and Western blotting results showed that curcumin inhibited inflammatory cytokine mRNA expressions by preventing p65 nuclear translocation without interfering with p38 and JNK/MAPK phosphorylation or IκBα degradation. Moreover, curcumin promoted PARP-1 cleavage and inhibited intranuclear lamina protein Lamin B1 expression. Flow cytometry results showed that curcumin enhanced Annexin V-FITC positive cells when LPS induced inflammation. This study provided evidence that curcumin inhibited p65 nuclear translocation and cytokine transcription by regulating nuclear protein structure and function, suggesting that early apoptosis involved the suppression of p65 nuclear translocation. 
    Effect of Huanglian Jiedu Decoction on vascular endothelium factor and expression of RhoA protein factor in young spontaneously hypertensive rats
    Nan Zhang, Yiwen Gao, Chanmei Lv, Xiaoli Yang, Guihua Yue
    2019, 28(2):  114-120.  DOI: 10.5246/jcps.2019.02.011
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    To investigate the mechanism of effect of Huanglian Jiedu Decoction (HLJD) on vascular endothelium, we assessed the protective effect of HLJD on vascular endothelium in spontaneously hypertensive rats (SHR) and the expression of RhoA in thoracic aorta. A total of 40 SHR rats were randomly and evenly divided into model group (SHR group), positive group (captopril group), HLJD high-dose group, and HLJD low-dose group. Simultaneously, 10 Wistar Kyoto rats were used in the blank group.All groups were treated by gavage for 6 weeks. The changes of nitric oxide synthase (NOS), von Willebrand factor (vWF), endothelin (ET-1) and calmodulin (CAM) in rat serum were tested by enzyme linked immunosorbent assay (ELISA) method. The expression of RhoA at the protein and mRNA levels in thoracic aorta was determined by Western blotting (WB) and quantitative real-time PCR, respectively. Compare with the blank group after 6 weeks, the levels of ET-l and VWF in serum of the model group were significantly increased (P<0.01), and the levels of NOS and CAM were significantly decreased (P<0.01). Conversely, the levels of ET-1 and vWF in the positive and HLJD groups were significantly decreased (P<0.01 or P<0.05), and the levels of NOS and CAM were significantly increased (P<0.01 or P<0.05) compared with the model group. The expression of RhoA at the mRNA and protein levels was decreased obviously (P<0.05) in HLJD high-dose group. The results shown that HLJDincreased diastolic factor (CAM and NOS) in the vascular endothelial of rats, leading to reduced contraction factor (ET-1 and vWF). HLJD revealed the preventive function in the vascular endothelial dysfunction of the early stage hypertension through adjusting secretion of blood vessel endothelium (BVE) relaxing factor and improving vascular endothelial function.The mechanism might be associated with the inhibition of the activity of RhoA protein factor.
    The cellular uptake and anti-tumor activity of conjugated linoleic acid-paclitaxel-loaded iRGD-modified lysolipid-containing thermosensitive liposomes
    Yanli Hao, Ting Zhong, Ruo Du, Hua Zhang, Bilin Liu, Xuan Zhang
    2019, 28(2):  121-133.  DOI: 10.5246/jcps.2019.02.012
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    In the present study, we prepared the iRGD-modified lysolipid-containing thermosensitive liposomes (LTSL) containing conjugated linoleic acid-paclitaxel (CLA-PTX), also known as iRGD-LTSL-CLA-PTX. The in vitro cellular uptake and invitro cytotoxicity of iRGD-LTSL-CLA-PTX were evaluated in B16-F10 melanoma cells. The in vivo anti-tumor effect of iRGD-LTSL-CLA-PTX was investigated using B16-F10 tumor-bearing C57BL/6 mice. The results of the cellular uptake experimentindicated that the increased cellular uptake of CLA-PTX in the iRGD-LTSL-CLA-PTX-treated groups was 2.05-, 3.31- or 4.83-foldcompared with that in the SSL-CLA-PTX group after a 2-, 4- or 6-h incubation at 42°C, respectively. The in vivo antitumor results showed that iRGD-LTSL-CLA-PTX/heat significantly inhibited the growth of B16-F10 tumors compared with the CLA-PTX solution (LTSL-CLA-PTX, LTSL-CLA-PTX/heat and iRGD-LTSL-CLA-PTX) (P<0.01). In conclusion, the antitumor effect of iRGD-LTSL-CLA-PTX was confirmed on B16-F10 melanoma in vitro and in vivo, which was induced by both the effect of iRGD and LTSL.
    Pharmacokinetic and pharmacodynamic comparison between Glucophage? and a generic metformin in a rat model
    Yan Yan, Ling Li, Rui Li, Wenjun Yu, Yi Han, Yukui Ma, Yan Li
    2019, 28(2):  134-142.  DOI: 10.5246/jcps.2019.02.013
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    In the present study, we aimed to compare the pharmacokinetics and pharmacodynamics between Glucophage® and a generic metformin formulation in a diabetic rat model in order to assess the bioequivalence of the generic formulation.Adult male Zucker diabetes fatty rats received Glucophage® or the generic metformin through gastric gavage at a dose of 180 mg/kg (n = 6 per condition). Both pharmacokinetic parameters (AUC0–t, AUC0–∞, Cmax) of metformin and plasma glucose levels were compared between the two groups. For pharmacodynamics, rats received Glucophage® or the generic metformin at doses of 180 and 300 mg·kg–1·d–1 for 6 weeks. The measurements included body weight, fasting plasma glucose, glycosylated serum protein (GSP) and serum insulin. Data were analyzed with SPSS 22.0 and Prism 7. The level of statistical significance was set at P<0.05.In single dosing experiments, pharmacokinetic parameters (t1/2, AUC0–t and Cmax) did not differ between Glucophage® and the generic metformin (P>0.05). However, plasma glucose was significantly higher in the generic metformin group at 2 h (P = 0.03) and 4 h (P = 0.04) after drug treatment. In repeated dosing experiments, fasting glucose, HOMA-IR and body weight in rats receiving high-dose Glucophage® were significantly lower at the end of the 6-week treatment period than those in rats receiving high-dose generic metformin (P<0.05 for all). GSP and serum insulin did not differ significantly between the two groups. In rats receiving low-dose metformin, fasting glucose was lower in the Glucophage® group. HOMA-IR and body weight did not differ between the two groups. Moreover, blood lipids did not differ significantly between the two groups. The generic metformin used in the current study did not differ significantly in pharmacokinetic characteristics with Glucophage®. However, Glucophage® was superior in terms of glucose control, body weight loss and insulin sensitivity in repeated administration.
    Other
    Information from US FDA
    http://www.fda.gov
    2019, 28(2):  143-144. 
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    The U.S. Food and Drug Administration today approved the first generic of Advair Diskus (fluticasone propionate and salmeterol inhalation powder) for the twice-daily treatment of asthma in patients aged four yearsand older and maintenance treatment of airflow obstruction and reducing exacerbations in patients with chronic obstructive pulmonary disease (COPD). Mylan obtained approval to market its generic inhaler in three strengths: fluticasone propionate 100 mcg/ salmeterol 50 mcg, fluticasone propionate 250 mcg/ salmeterol 50 mcg and fluticasone propionate 500 mcg/ salmeterol 50 mcg