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  • Hong-die CAI, Wei-wei TAO, Shu-lan SU, Sheng GUO, Yue ZHU, Jian-ming GUO, Da-wei QIAN, Xu-dong CONG, Ren-mao TANG, Jin-ao DUAN
    Acta Pharmaceutica Sinica. 2017, 52(2): 222-228.

    Abelmoschus manihot (L.) Medic., a folk herbal medicine in China, is a flowering plant belonging to Abelmoschus L. genus and Malvaceae family, which has been reported with an antidepressant activity. The study was designed to isolate flavonoids from Abelmoschus manihot corolla and explore the action mechanism of antidepressant activities. The flavonoids were isolated and purified by D101 macroporous resin column, polyamide column and Sephadex LH-20 sequentially and identified as myricetin-3-O-β-D-glucoside (1), gossypetin-8-O-β-D-glucuronide (2, G-8-G), gossypetin-3'-O-β-D-glucoside (3), quercetin-3'-glucoside (4, Q-3-G), isoquercitrin (5, IQT), hyperoside (6, HY), myricetin (7), quercetin (8, QT). Compounds 2, 4, 5, 6 and 8 (15, 30 and 60 mg·kg-1) were orally administered to mice and the reaction was observed in tail suspension test (TST) and forced swimming test (FST). Western blot analysis was used in determination of the protein expressions of brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB) and phosphorylation eukaryotic elongation factor 2 (p-eEF2). The results revealed that only Q-3-G and G-8-G (15, 30, 60 mg·kg-1) significantly reduced the immobility time in FST and TST. Furthermore, Q-3-G and G-8-G remarkably increased the expression of BDNF and TrkB, and decreased the expression of p-eEF2. These results suggest that Q-3-G and G-8-G had an obvious antidepressant activity via up-regulation of BDNF expression. The new observation will provide a new direction in the development of antidepressant in the treatment of major depressive disorder (MDD).

  • Jin TAO, Min JIANG, Lu-ying CHEN, Yuan-yuan HOU, De-qin ZHANG, Feng QIU, Gang BAI
    Acta Pharmaceutica Sinica. 2017, 52(2): 236-244.

    Property and flavor theory of traditional Chinese medicine (TCM) is the core base for clinical treatment of diseases. However, few research about its chemical and biological characterization was performed. In this paper, network pharmacology was adopted to review patterns around the theory of TCM. "Xiaoke" prescription database, which combinations of herb medicines for diabetes therapy, was firstly built to explore prescription regularity and screen core paired-components. The prescription regularity and molecular mechanism of flavor composition were explored through the relationship of "drug-compound-target-pathway-function" by ChEMBL, CTD and KEGG datebase. As a result, the tastes of "Gan" (sweetish taste) and "Ku" (bitter taste) were the popular therapeutic flavor to regulate the disorder of glucose and lipid metabolisms. The mechanism of Xiaoke was summarized from representative traditional Chinese medicine partner "Zhimu-Huangbai" and "Huangqi-Gegen". The key components of "Gan", including saponins stimulated insulin secretion, improve insulin resistance and promote glucose utilization. The components of "Ku", including flavonoids and alkaloids regulate inflammatory cytokines, promoted the utilization of glucose, improve endocrine and metabolism through MAPK, PI3K-Akt, PPAR signal pathway. The TCM therapeutic mechanism about "Xiaoke" was preliminarily summarized to clear "heat" by anti-inflammation and immunoregulation, to regulate glucolipid metabolism for removing the satiation of digestion, and to improve the utilization of insulin and diabetes complications for endocrine adjusting. The results demonstrate that therapeutic principle of TCM for "Xiaoke" is comprehensive via multi pathway. This study provides a new research method and strategy for exploring the mechanism of TCM for diabetes therapy.

  • Guang-zhao LU, Cheng HOU, Yan-qiang ZHONG, Ying LU, Hao ZOU
    Acta Pharmaceutica Sinica. 2017, 52(2): 206-213.

    Excessive reactive oxygen species (ROS) is associated with an array of pathological conditions, including cancer, diabetes, cardiovascular diseases, and neurodegenerative diseases. However, ROS-responsive materials have drawn attention in the development of drug delivery systems. There are many types of ROS-responsive materials explored in drug delivery applications, including sulfur-based responsive polymers, selenium-based responsive polymers, tellurium-based responsive polymers, oxalate ester-containing polymers, phenylboronic ester-containing polymers and unsaturated lipids. When integrated with ROS-responsive drug delivery systems, a photosensitizer is used as a light-sensitive element to generate ROS, mainly singlet oxygen (1O2), which in turn activates the ROS-triggered drug delivery.

  • Yu SONG, Hui ZHANG, Rui-li LIU, Guang-fan HAI, Tong WANG, Jia-xin YUE, Wei-li ZHANG, Yu-ke REN
    Acta Pharmaceutica Sinica. 2017, 52(2): 229-235.

    Postoperative intra-abdominal adhesion is one of the most common complications in the postoperative period. Current remedies are very ineffective to prevent the pathological outcomes except steroid hormones. Rhynchophylline is deemed as a pharmacologically active component from traditional Oriental medicine Uncaria rhynchophylla (Miq.) Jacks. (Rubiaceae). This study was designed to investigate the preventative effect of rhynchophylline on the abdominal adhesions in rats. Rhynchophylline relieved the experimental abdominal adhesion and decreased the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the blood serum in a dose-dependent manner. The levels of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) were reduced significantly in the peritoneal fluid. The potential mechanism of the activity is related to inhibition of the TGF-β1/Smad signaling pathway.

  • Zi-rui WANG, Feng BAI, Xiao-ying ZHANG, Jia-min WU, Ling GUO, Zhi LI, Min FENG
    Acta Pharmaceutica Sinica. 2017, 52(2): 309-317.

    This study was designed to reverse multidrug resistance of lung cancer cells by downregulating MDR1 genes through RNA interference (RNAi) technology. A novel biodegradable cationic polymer (PEG-b-PLG-g-PEIs, GGI) was synthesized and characterized by 1H NMR. The particle size and zeta potential were measured by dynamic light scattering (DLS). The cell viability profile of GGI was tested by MTT method with both A549 and A549/DDP cell lines. Flow cytometry (FCM) technology was used to investigate the efficiency and intensity of delivering siRNA to cells by GGI polymer. RT-PCR and Western blot were used to detect the mRNA and P-gp expression after GGI/MDR1 siRNA transfection assay. The sensitivity of cisplatin administration after transfecting GGI/MDR1 siRNA polyplexs was performed with MTT and Annexin V-FITC/PI methods. The results suggest that the particle size and zeta potential of GGI/siRNA were 150-200 nm and 16-28 mV. GGI exhibited a lower cell cytotoxity than PEI 25K and higher efficiency of delivering siRNA, which dramatically decreased the expression of MDR1 mRNA and P-gp of A549/DDP cells and increased much sensitivity to cisplatin in A549/DDP cells. GGI holds a great potential in gene delivery as a novel cationic polymer for further investigation.

  • Shuai CHEN, Yuan-yuan XIA, Guang-li WEI, Quan-sheng LI, Meng-jie LIU, Yong CHEN, Duan-yun SI
    Acta Pharmaceutica Sinica. 2017, 52(2): 296-301.

    A pre-column derivatization method combined with UHPLC-MS/MS was developed for the simultaneous determination of salidroside and tyrosol in Beagle dog plasma. After protein precipitation by acetonitrile, the liquid supernatant was treated with dansyl chloride under dark conditions at 60℃ for 30 min, and then, the sample solution was extracted using methyl tertiary butyl ether. The multiple reaction monitoring in positive ion mode was used for MS detection of the tested analytes with the specific ion transitions of m/z 534.2→372.0 for salidroside derivative, m/z 372.0→171.0 for tyrosol derivative and m/z 506.0→171.0 for arbutin derivative. The chromatograph separation was achieved on an ACQUITY UPLC® BEH C18 column (100 mm×2.1 mm, 1.7 μm) with a gradient mobile phase consisting of acetonitrile (0.1% formic acid)-water (10% acetonitrile, 0.1% formic acid) for 9 min. The assay showed a good linearity over the range of 0.02/0.1-20/10 μmol·L-1 with a lower limit of quantitation of 0.02 and 0.1 μmol·L-1 for salidroside and tyrosol in dog plasma, respectively. The intra-and inter-day precisions were all less than 8.68%, and the accuracy was within ±11.4%. The established method with a high sensitivity, good specificity and reliability was appropriate for simultaneous determination of salidroside and tyrosol in dog plasma and successfully applied to a pharmacokinetic study after intragastric administration of salidroside to Beagle dogs.

  • Jin-long CUI, Shun-xing GUO, Pei-gen XIAO
    Acta Pharmaceutica Sinica. 2017, 52(2): 214-221.

    Research of plant development and metabolism has drawn lots of attention with the fast development of science of mycorrhizal biology, molecular biology and metabonomics technology. It has become one of hot fields in the study of endophytes and plant, which would affect plant's metabolite composition. This would provide opportunity for appraising and modifying traits to medicinal plant, and would also perfect the tranditional standpoint on forming reason of medicinal plant genuineness. Here we provide a review of theory and mechanism, research and application of interaction between plant and endophyte. This review may enhance understanding of medicinal plant, and evaluating the quality of herbs in production.

  • Xiao-yan HE, Jian-li CHEN, Huan XIANG, Yao GAO, Jun-sheng TIAN, Xue-mei QIN, Guan-hua DU
    Acta Pharmaceutica Sinica. 2017, 52(2): 245-252.

    This study was designed to analyze the change of metabolites in the PC12 cells and its medium induced by corticosterone (CORT) and glutamate (Glu) by proton nuclear magnetic resonance (1H NMR) metabolomics. The multivariate statistical analysis was employed to identify the difference between control groups and induced groups, respectively. In addition, metabolite pathway analysis was performed to explore the characteristic of CORT-induced and or Glu-induced PC12 cells depression model, and to provide the references for the selection of in vitro depression models as well as the further understanding of the mechanism on depressive disorders. We found 36 differential metabolites in CORT-induced PC12 cells and medium and 42 in Glu-induced PC12 cells. Furthermore, correlation analysis results show that serine and 2-oxoisoleucine were associated with most differential metabolites in CORT-induced PC12 cells. Lactate and glutathione were significantly correlated to the vast majority of differential metabolites in Glu-induced PC12 cells. We speculated that CORT-induced PC12 cell models may affect the fatty acid metabolism and cell membrane structure, and Glu-induced PC12 cell models may have a difference in the glycolysis and antioxidants.

  • Zhao-yi ZHONG, Min WU, Shuai QIAN, Jian-jun ZHANG, Yuan GAO
    Acta Pharmaceutica Sinica. 2017, 52(2): 302-308.

    Puerarin (PUE), an isoflavone with anti-inflammation, anti-oxidation and neuroprotection effects, has been widely applied to the treatment of cardiovascular diseases in clinics in China. In the current study, we reported that the active pharmaceutical ingredient (API) of marketed products was the PUE monohydrate (PUEMH). During its supersaturated dissolution, the PUE concentration quickly reached a plateau, followed by a gradually concentration decrease to another lower plateau. In order to explore the internal mechanism of above phenomenon, the solid residues after saturated dissolution test were characterized by powder X-ray diffraction (PXRD), thermal gravity analysis (TGA) and Karl Fisher titration (KFT). PXRD suggested that a novel PUE crystal different from PUEMH formed during its dissolution, the following TGA and KFT confirmed the generation of PUE dihydrate (PUEDH) with much lower solubility. Moreover, polyvinylpyrrolidones (PVPK12, PVPK30 and PVPK90) were added in the dissolution medium to investigate their potential inhibition effects on such crystal transformation during dissolution process. We observed that polymers could inhibit the transformation from PUEMH to PUEDH and result in much higher PUE concentration level than that in pure water.

  • Meng-meng LIU, Yong-mei XING, Shun-xin GUO
    Acta Pharmaceutica Sinica. 2017, 52(2): 327-332.

    A type Ⅱ ribosome inactivating protein (RIP) gene was cloned from Polyporus umbellatus sclerotia by RT-PCR method. The full open reading frame cDNA sequence of this gene was 873 bp in length and encoded a 290-aa protein with a molecular weight of 32.33 kDa and an isoelectric point of 5.58. Multiple sequence alignment revealed that the deduced amino acids possessed conserved domains of RICIN superfamily protein. A neighbor joining phylogenetic analysis suggests that PuRIP was closely related to RIP in Marasmius oreades. Real time PCR results showed that this gene expressed in all tested tissues of P. umbellatus. Meanwhile, the expression of this gene was significantly up-regulated in the part infected by Armillaria mellea. This result suggested that this PuRIP might played important role with potential biotic stress tolerance of P. umbellatus. Otherwise, we successfully constructed the pET15b-PuRIP plasmid, produced and purified the His-PuRIP fusion protein, which would provide the basic material for polyclonal antibody preparation and gene function research.