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  • Yi-xuan ZHANG, Rong-guang SHAO, Hong-wei HE
    Acta Pharmaceutica Sinica. 2017, 52(11): 1647-1651.

    Integrin is a class of important cell surface molecules involved in cell proliferation, differentiation, adhesion and migration processes, which play an important role in a variety of pathological processes. In recent years, with the research in integrin regulation and the treatment of tumor, tissue fibrosis, and other fields, integrin has gradually become a new target in the diagnosis and treatment of diseases. In this article, we provide a summary on the advances of the regulation of integrin gene expression.

  • Ti-ying CHEN, Juan LIU, Yuan YUAN, Jun-hui ZHOU, Lu-qi HUANG
    Acta Pharmaceutica Sinica. 2017, 52(11): 1770-1776.

    Auxin response factor (ARF) is an important transcription factor for auxin signal transduction pathway, which regulates virtually every aspect of plant growth and development from embryogenesis to senescence. Nine full-length genes of ARF transcription factors were obtained from transcriptome dataset of Scutellaria baicalensis Georgi using the bioinformatics methods. The nucleotide and protein characteristics, subcellular localization, senior structural domains and conservative forecasts of those ARF transcription factors were analyzed. The phylogenetic tree showed that the nine ARFs in S. baicalensis were clustered together with ARF transcription factors in Arabidopsis thaliana, Oryza sativa subsp. Japonica and Nicotiana attenuate. The results of gene expression showed that:① The expression levels of ARF1, ARF3, ARF4, ARF8, ARF20 and ARF24 were upregulated after 100 μmol·L-1 GA3 treatment. However, the expression levels of ARF6 and ARF18 were downregulated; ② Those ARF genes were mainly expressed in the flowers of S. baicalensis; ③ There was a significant correlation between ARF genes and the genes involved in flavonoid biosynthesis. Our results provide a basis for further understanding the molecular regulation mechanism of flavonoid biosynthesis in S. baicalensis.

  • Hai-jun SHEN, Zhi-juan WU, Dong-xia WANG, Dong-fang HUO, Yu BAI, Zhi-han YANG, Chun-fang YAO
    Acta Pharmaceutica Sinica. 2017, 52(11): 1748-1755.

    This study aims to establish a novel gene-activated matrix that mimics the structure and function of extracellular matrix (ECM-m-GAM). The structure, mechanical property and release profile were also characterized. Firstly, the liposome/DNA lipoplex (LPD) was modified with cell penetrating peptide TAT. The obtained TAT-LPD was then mixed with RGD grafting hyaluronic acid solution. After addition of the matrix metalloproteinase (MMPs) sensitive crosslinker (HS-MMP-SH), hyaluronic acid was crosslinked and TAT-LPD was encapsulated in the subsequently formed hydrogel. As a result, the cell adhesion factor RGD, MMPs sensitive substrate and the efficient gene transfer vector TAT-LPD were all integrated in the hyaluronic acid hydrogel, which was named as ECM-m-GAM. The release profile of DNA from ECM-m-GAM in different release medium was evaluated with PicoGreen kits. The results suggested that the mean diameter of the spherical TAT-LPD was (263.0 ±4.30) nm. TAT-LPD was successfully encapsulated in ECM-m-GAM, which had the typical porous network structure of hydrogels. The mechanical strength of GAM was enhanced with the increasing of hyaluronic acid content. When the content was 4%, the elastic modulus of GAM reached 1 600 Pa. The highly elastic GAM may be suitable for implantation and tissue regeneration. The DNA release showed significant MMPs sensitive property. Especially, the released DNA still existed in form of nanoparticles. Bone marrow mesenchymal stem cells (BMSCs) were successfully transfected with GAM and the green fluorescent protein was expressed. The results have laid a solid foundation for future study of the cell transfection and tissue regeneration.

  • Yang ZHANG, Yu YANG, Jia-ming LI, Xiao-dong MA, Yan-chun ZHANG, Yu-jun WANG, Pan-hu ZHU
    Acta Pharmaceutica Sinica. 2017, 52(11): 1722-1730.

    Using ligustrazine as the leading compound, we designed and synthesized ten novel ligustrazine derivatives, whose structures were determined by 1H NMR, 13C NMR and MS. Inhibitory effects of the new compounds on the proliferation of A549, A549/DDP and HBE cells were detected by MTT assay. The inhibi-tory activity of the synthesized compounds on migration and invasion of A549 cells were evaluated through scratch assay and transwell assay. Mechanism of the inhibition on migration and invasion was investigated by Western blotting. In addition, the cell cycle was analyzed with flow cytometry. The results showed that, both compounds Z8 and Z10 have an anti-proliferative activity, and the potencies of inhibition of tumor-cell migration and invasion were attributed to the down-regulation of MMP-2 and MMP-9. The compounds Z8 and Z10 could also enhance G2/M arrest in A549 cell as revealed by cell cycle analysis.

  • Xin-xin DAI, Hong-die CAI, Shu-lan SU, Tian-yao ZHENG, Dan-dan WEI, Hui YAN, Yue ZHU, Da-wei QIAN, Jin-ao DUAN
    Acta Pharmaceutica Sinica. 2017, 52(11): 1683-1691.

    The aim of this study was to investigate the regulatory effect of the total glycoside extracted from leaves of Rehmannia (TLR) and Dihuangye total glycoside capsule (DTG) on intestinal microflora in diabetic nephropathy rats. Forty-eight rats were randomly divided into the control group (C), model group (M), Huangkui capsule group (0.75 g·kg-1·d-1, HK), irbesartan group (27 mg·kg-1·d-1, YX), TLR low dose group (4.3 g·kg-1·d-1, DHYL), TLR high dose group (7.2 g·kg-1·d-1, DHYH), DTG low dose group (216 mg·kg-1·d-1, JNL), DTG high dose group (360 mg·kg-1·d-1, JNH). Rat model of diabetic nephropathy was induced by intraperitoneal injection of small dose of streptozotocin (45 mg·kg-1, STZ) and feeding high-fat diet and 5% glucose drinking water. After oral administration for two weeks, the 16S rDNA sequencing method was used to study the effects of the TLR and DTG on intestinal flora in diabetic nephropathy rats. The results showed that compared with the control group, the intestinal flora of diabetic nephropathy rats had changed from phylum units to the genus units. Moreover, the proportion of lactobacilli in the intestinal bacteria of the model group was significantly decreased, and the proportion of lactobacilli in the administration group was increased, especially the YX group, TLR low dose group and DTG low dose group. The data suggest that the total glycosides of Rehmannia glutinosa improved the disorder of intestinal flora in STZ-induced diabetic nephropathy rats.

  • Cai-ying PENG, Ying-zheng HUANG, Jian-qun LIU, Hui-lian HUANG, Ji-cheng SHU
    Acta Pharmaceutica Sinica. 2017, 52(11): 1731-1736.

    To investigated the chemical constituents of the roots of Psidium guajava, we isolated seven compounds by silica gel column chromatography.These include oleanane derivatives, 2 α, 3β, 6β, 23-tetrahydroxylurs-12, 20(30)-dien-28-oic acid β-D-glucopyranoside (1), 2α, 3β, 6β, 23-tetrahydroxylurs-12, 18-dien-28-oic acid β-D-glucopyranoside (2), 2α, 3β, 23-trihydroxylurs-12, 18-dien-28-oic acid β-D-glucopyranoside (3), nigaichigoside F1(4), asiaticoside C (5), 2α, 3β, 6β, 19α, 23-pentahydroxylurs-12, 18-dien-28-oic acid β-Dglucopyranoside (6) and 2α, 3β, 19α, 23-tetrahydroxylurs-12-en-28-oic acid (7).Their structures were elucidated on the basis of spectral analysis with reference to the published data.Compound 1 is brand new, compounds 2-6 were first isolated from this plant.The new compound was evaluated for their cytotoxic activity against human hepatoma Bel 7402 in vitro.The results were expressed as the ratio of inhibiting Bel 7402 cells growth by comparing to untreated cells.The new compound (concentration:25 μmol·L-1) showed the ratio values of 52.5%.

  • Bing-feng LUO, Jun ZHANG, Tao YANG, Juan-hong ZHANG, Wen-bin LI, Chang WANG, Ming-xia ZHANG, Rong WANG
    Acta Pharmaceutica Sinica. 2017, 52(11): 1715-1721.

    The relationship between PEPT1 (peptide transporter) and drug efficacy has drawn more and more attention in the treatment of disease. PEPT1 represents a promising strategy for improvement of drug bioavailability and an important starting point for clinical rationalization of drug selection. The effect of PEPT1 on transport and pharmacokinetics of amoxicillin was investigated under hypoxia condition at high altitude in rat. The mRNA and protein expressions of PEPT1 were increased by 36.87%, 216.21%, 577.8% and 535.9% respectively in the hypoxia group in the small intestine and kidney of rats. However, the mRNA and protein expressions of PEPT1 were reduced by 43.90% and 84.7% in the liver. Compared with the control group, the AUC, tmax, Cmax, MRT and t1/2 of amoxicillin were significantly enhanced by 312.17%, 63.04%, 110.93%, 67.11% and 16.96% respectively in the hypoxia group, while the CL was significantly decreased by 74.51%. After acute exposure to high altitude, the expressions of drug transporter PEPT1 were distinctly changed in rat tissues, which can affect the pharmacokinetics of amoxicillin.

  • Zu-yue DENG, Yu-ping YUAN, Long-fei LÜ
    Acta Pharmaceutica Sinica. 2017, 52(10): 1541-1548.

    To study the effects of squalene on behavior and related proteins of glutamate toxicity pathways in the mice with chronic unpredictable mild stress (CUMS), thirteen different kinds of CUMS were applied to the male BALB/C mice for 35 days to establish the mouse model of CUMS depression. The stress conditions include food deprivation, noise, stroboscopic lighting, hot stress (45℃), brake, exposure to lower temperature (4℃), shake, soiled cage, clamp tail, water deprivation, swimming, electric shock, presence of a foreign object in the home cage. The mice were treated with squalene at 3 doses (80, 40 and 20 mg·kg-1·d-1) through oral administration from the 3rd week continuously. Three weeks later, the impacts were evaluated in the mice with behavioral tests, and malondialdehyde (MDA) and hippocampal glutamate (GLU) contents, the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity in hippocampus were measured by spectropho-tometry or reversed phase HPLC (RP-HPLC). Western blot was used to examine the expression level of N-methyl-D-aspartate receptor subunits epsilon-2 (NMDAε2), calmodulin kinaseⅡ (CaMKⅡ) and neuronal nitric oxide synthase (NOS1) in hippocampus. Compared with model group, the squalene-treated mice exhibited an increase in body weight, sucrose preference rate and the times of crossing-movement and rearing-movement, shortened the immobility time in the tails suspension test and forced swimming test in the depression mice (P < 0.05). Meanwhile, the treated mice had a significant decrease in the contents of GLU and MDA (P < 0.05) in hippocampus, increased the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and downregulated the expression of NMDAε2, CaMKⅡ and NOS1 in the hippocampus. In conclusion, squalene shows anti-depressant effect on depressant model in mice, meanwhile the downregulated ROS, related proteins of GLU-NMDAε2-CaMKⅡ-NOS1 signal pathways may be related to the antidepressant effect of squalene.

  • Hao-zhou HUANG, Ding-kun ZHANG, Hong JIANG, Jun-zhi LIN, Ya-nan HE, Run-chun XU, Ming YANG, Li HAN
    Acta Pharmaceutica Sinica. 2017, 52(10): 1524-1532.

    Anthocyanins has a high health benefits and biological activity, which can make the solution easily absorbed and has a bright color, beautiful appearance in oral liquid. However, due to its particularity antioxidant activity, it is easy to be affected by the external physical and chemical factors, and then oxidation, polymerization, degradation and other unstable phenomena occurs that seriously affect the stability of products and shelf life. The traditional methods of pH regulation, deoxygenation and light avoidance could not meet the demand of stable anthocyanins. Addition of stabilizer to anthocyanins is a new effective way to improve the stability of anthocyanins. This paper is prepared to summarize systematically the principle and application methods of anthocyanins stabilizers to explore the key technology of clarification and stabilization of traditional Chinese medicine in the natural oral liquid, which may provide theoretical support and technical reference for the development and utilization of anthocyanins stabilizer.

  • Zhi-yu CHEN, Shuai-nan LIU, Zhen-hua LUO, Su-juan SUN, Zhu-fang SHEN, Ying-jie NIE
    Acta Pharmaceutica Sinica. 2017, 52(10): 1561-1567.

    To investigate the effects of metformin on pancreatic β-cell function and its possible mechanism, high fat diet-induced type 2 diabetic C57BL/6J mice were divided into two groups according to fasting blood glucose (FBG), glucose decreasing rate at 40 min of insulin tolerance test, triglycerides (TG), cholesterol (CHO) and body weight (BW). The C57 mice were gavaged with water or metformin for 58 days. β-Cell function was evaluated by oral glucose tolerance test and hyperglycemic clamp. Genes and proteins related to pancreas proliferation, lipid metabolism and endoplasmic reticulum stress were investigated. Compared with the model group, metformin group exhibited a reduction in the body weight (P < 0.01), plasma TG and CHO (P < 0.05), and the area under the curve (AUC) (P < 0.05) of glucose tolerance test. The glucose infusion rate during clamp was improved (P < 0.05) and the fasting insulin level was decreased in the metformin group (P < 0.05). Metformin significantly upregulated the gene expression of pancreatic and duodenal homeobox 1 (Pdx-1, P < 0.01) and liver X receptor β (Lxr-β, P < 0.01). Western blot results showed that, the protein expression of PDX-1 was significantly upregulated (P < 0.01). Endoplasmic reticulum stress related protein of activating transcription factor 4 (ATF4, P < 0.001) and C/EBP homologous protein (CHOP, P < 0.05) were also down-regulated. These results suggest that metformin could improve the insulin secretion function of type 2 diabetic C57BL/6J mice. The mechanism of the action may rely on its improvement of pancreas cell proliferation, lipid metabolism and amelioration of endoplasmic reticulum stress.