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  • Jin-feng SHI, Jie LI, Xiao-qin YANG, Yue ZHANG, Shi-cai YANG, Yao-yao LUO, Jin-ming ZHANG, Chao-mei FU
    Acta Pharmaceutica Sinica. 2019, 54(2): 258-268.

    Anti-tumor intervention using a combination of drugs shows unique advantages in research and clinical practice. Active ingredients of Chinese herbal medicines can offer many advantages, such as high efficiency, low toxicity, wide effect and multiple targets. At present, the combination active ingredients of Chinese herbal and chemotherapy drugs have attracted increased attention. Nano-drug delivery system provides a good carrier platform for anti-tumor drugs. Nano-carrier-mediated drug combination is a promising strategy. In this paper, we review the mechanisms of the anti-tumor effects of active ingredients of traditional Chinese medicine combined with chemotherapeutic drugs and consider the advantages of drug-loaded nanoparticles, the types and characteristics of carriers. The aim is to provide a reference for the research of effective regimen for anti-tumor therapy.

  • Rong ZHAO, Jun JIANG, Shi-chang XIAO, Chao-lin TAN, Fu-yuan WANG, Xi-ming XU, Hai-jian XIA
    Acta Pharmaceutica Sinica. 2019, 54(2): 313-320.

    To assess the therapeutic effect of Tao Hong Si Wu decoction (THSWD) on glucocorticoid-induced osteoporosis and its mechanism, the standard products of nine active components in THSWD were accurately weighed and the reserve liquid of standard product was prepared. Then a series of concentration standard liquid was obtained by dilution, and the standard curve was established. The formula of THSWD was proportionally extracted and the nine active components were determined by high performance liquid chromatography (HPLC). Naturally mated to obtain zebrafish embryos after incubation, the zebrafish larvae were cultured in blank E3 medium until the 3 days post fertilization (DPF), then divided into control group (blank E3 medium), prednisolone (PNSL) group (25 μmol·L-1 PNSL), disodium ethydronate (DE) group (15 μmol·L-1 DE and 25 μmol·L-1 PNSL), THSWD group (0.1, 1.0 or 10.0 μg·mL-1 THSWD and 25 μmol·L-1 PNSL), 15 in each group. The culture was continued until the 10 DPF. The zebrafish was anesthetized and sacrificed, stained with alizarin red S, then the bone staining was observed under a microscope. Quantitative analysis of bone mineralization area and cumulative optical density. Expression of alkaline phosphatase (AKP), type Ⅰ collagen (type Ⅰ), runt-related transcription factor 2 (RUNX-2), osteoprotegerin (OPG), tartrate-resistant acid phosphatase 5b (TRACP) and osteocalcin (OCN) were assessed by quantitative real-time PCR. The mineral contents in zebrafish were measured using inductively coupled plasma-mass spectrometry. In the THSWD water extract, the content of 9 compounds in descending order was as follows:gallic acid > hydroxysafflor yellow A > chlorogenic acid > senkyunolide H > ferulic acid > caffeic acid, senkyunolide Ⅰ > coumaric acid > benzoic acid. Compared with the control group, treatment of zebrafish with 25 μmol·L-1 prednisolone significantly reduced the area of mineralized bone and cumulative optical density, and the expression of AKP, type Ⅰ, RUNX-2, OPG, OCN gene was also significantly reduced. The levels of Ca, P, K, Mg, Zn and Fe in zebrafish were reduced by 2.8, 2.4, 13.8, 6.6, 8.0 and 8.8 times, respectively. Compared with the prednisolone group, after treating with THSWD, the area of mineralized bones and cumulative optical density value of zebrafish increased significantly and was dose-dependent, and the expression of related genes also increased. The Ca, P, K, Mg, Zn, Fe levels were significantly higher than the prednisolone group. Result show that THSWD has the potential to reverse the effect of glucocorticoid osteoporosis, the mechanism of which is to enhance the activity of osteoblast, promote the expression of bone gelatin and bone mineralization, and increase bone mass.

  • Xiao-tao HOU, Er-wei HAO, Zheng-cai DU, Zhong-shang XIA, Jia-gang DENG, Tie-jun ZHANG, Chang-xiao LIU
    Acta Pharmaceutica Sinica. 2019, 54(2): 211-221.

    The quality definition of traditional Chinese medicine (TCM) is a hot area in modern research of TCM. In recent years, the characteristics of one herb with multiple effects have been widely accepted and studied. The typical opposite-effect of herbs is considered as a special part of one herb with multiple effects, and was summarized in this paper. Sanqi was used as an example of opposite-effect herbs for developing the strategies and approaches on the Q-markers. The traditional opposite-effect should be studied by modern pharmacological research methods. The correlation of the chemical components with the opposite effects should be established in order to verify the material basis and evaluate the mechanism including targets and pathways. The unique characteristics of chemical components should be analyzed and defined. Finally, the Q-markers of the opposite effect herb will be confirmed. This paper provides a useful reference for the precise quality control of herbal opposite-effects.

  • Xiu-mei ZHANG, Jia-jun CUI, Yin-jie JIANG, Nan-yan FU, Jing YANG, Zhi-xing ZHOU, Ning-yuan ZHANG, Kai QIAN
    Acta Pharmaceutica Sinica. 2019, 54(2): 380-385.

    Hypophosphatemia is a common metabolism disease in humans. Fibroblast growth factor 23 (FGF23) inhibits phosphate reabsorption by targeting on the renal tubules. FGF23C-tail contains 73 amino acids from C-terminus of FGF23, serves as an inhibitor of FGF23, and can increase phosphate reabsorption. Therefore, FGF23C-tail is an important drug for hypophosphatemia. In this paper, we constructed a fusion protein of FGF23C-tail with HSA, and investigated the expression of the fusion protein in the Pichia pastoris system. The recombinant gene was constructed by fusion PCR. A high-yield strain was selected by G418 resistance and fermentation yield, and the expression yield was 43.7 mg·L-1 in flask. In 5 L fermenters, the highest expression yield could reach 265.6 mg·L-1. FGF23C-tail-HSA could be used as an inhibitor for FGF23, and could significantly increase blood phosphorus levels in rats. The procedures for care and use of animals were approved by the Ethics Committee of YiChun University. This paper provided a basis research for further studying physiological activity of FGF23C-tail-HSA.

  • Qiao-bei PAN, Jing ZHANG, Xiang LI, Yuan-ying FANG, Yi JIN
    Acta Pharmaceutica Sinica. 2019, 54(2): 366-372.

    In this paper, multifunctional silver-graphene quantum dot nanoparticles coated with phospholipids (ADG-DDPC) were prepared and their properties were evaluated in vitro. Cationic phospholipids 1, 2-diolefinoxy-3-trimethy-laminopropane (DOTAP) was absorbed first onto the surface of the core of silver nanoparticle (AgNPs) through the mutual attraction between the positive and negative charge. Based on the principle of phase transformation and hydrophobic interaction, dstearyl-phosphatidylglycolamine-polyethylene-glycol-cyclic-cRGD peptide (DSPE-PEG2000-cRGD) self-assembled onto the outlayer of DOTAP of AgNPs. A stable multifunctional nano-preparation was formed and its ultraviolet absorption, particle size distribution, morphology, in vitro release behavior, ability to kill cancer cells and cell uptake were studied. The maximum UV absorption of the synthesized nanometer preparation was about 400 nm. Malvern particle size meter and transmission electron microscope showed that the particle size of the nano-preparation was about 30-40 nm and its particle size distribution was uniform. The in vitro release of nano-preparation was positively correlated with the concentration of H2O2. The IC50 value of AgNPs for tumor cells was (347.78±0.06) ng·mL-1, and the IC50 value of ADG-DDPC for tumor cells was (209.68±0.09) ng·mL-1, indicating that ADG-DDPC possessed a stronger cytotoxicity than that of AgNPs. Cell uptake experiment showed that ADG-DDPC could be absorbed by tumor cells and exhibited fluoresce inside those cells. In conclusion, ADG-DDPC was successfully prepared, and in vitro characterization study pointed to that the nano-preparation exhibits a higher antitumor activity than AgNPs.

  • Shi-wei ZHU, Xiao-xia GAO, Jun-sheng TIAN, Xue-mei QIN, Guan-hua DU, Yu-zhi ZHOU
    Acta Pharmaceutica Sinica. 2019, 54(2): 235-244.

    Depression, a global disease with various pathogenic factors, is seriously affecting human physical and mental health. In Chinese traditional medical theory, the disease belongs to the category of "Yu Zheng". At present, on the one hand, adverse reactions to antidepressant western medicine are becoming more and more prominent. On the other hand, the study of their antidepressant active ingredients and compatibility mechanisms has become a difficult field in the traditional Chinese medicine compounds due to their complexity. The Chinese antidepressant herb-pairs has become a hot topic in the field of antidepressant research. Herb-pair is the core of traditional Chinese medicine compound. In addition, the compound itself is a herb-pair. The study of traditional Chinese antidepressant herb-pairs is more conducive to clarify the compatibility mechanism of herb interaction and the mechanism of antidepressants on the body.Therefore, this paper systematically expounds antidepressant herb-pairs from the study of material, pharmacokinetics and efficacy, which aims at providing theoretical support for the compatibility mechanism of antidepressant herb-pairs and the research of new antidepressant drugs.

  • Ying WANG, Wei-yi XU, Li-xiao LI, Hong-yu JIN, Jian NI, Shuang-cheng MA
    Acta Pharmaceutica Sinica. 2019, 54(2): 348-353.

    To determine relative molecular weight of astragalus polysaccharides (APs), we used Shodex GS620 gel permeation chromatographic column and differential refraction detector (GPC-RI) with dextran as a reference. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and GPC combined with multi-angle laser light scattering detection (GPC-MALLS) were also used.GPC-RI measure showed four peaks of APs, with the Mw of 1 380 000, 231 000, 18 000, and 480, respectively. Three main peaks were found by GPC-RI-MALLS with the Mw as 1 148 000, 180 000, and 43 000, respectively. Strong signals in 155 000 and 18 000 were detected by MALDI-TOF-MS, which also indicated the sugar moieties of the APs as hexoses. From our study, we found that the GPC-RI method with universal correction is most suitable for Mw determination of the APs. Nevertheless, the three methods should be combined and contrasted with each other to obtain accurate information in research of polysaccharides from Chinese medicine.

  • Jing CHEN, Zhen XU, Xue ZHANG, Yan-peng LI, Chun-sheng LIU
    Acta Pharmaceutica Sinica. 2019, 54(2): 373-379.

    In order to determine the differences in structure and optimum isolation conditions of Glycyrrhiza uralensis endophytes from different habitats, plate-separation method was used to identify endophytes in G. uralensis from Gansu, Ningxia, Inner Mongolia, Xinjiang, and Beijing. The isolation parameters were defined by investigating various concentrations and sterilization time of NaClO solution. The strains were identified by morphological and molecular biological methods. The results showed that 5% NaClO solution and sterilization time of 5 min were the optimal surface sterilization conditions. Among 129 strains of G. uralensis from 5 producing areas, 438 strains of endophytic fungi were isolated and belonged to 5 orders, 7 genera, and 11 species. Among them, 4 taxa were firstly isolated from the licorice in China. Fusarium was a common genus among the 5 regions. There were differences in the composition and structure of the endophytic fungi of G. uralensis from different habitats. Diversity analysis showed that the endophytic fungi diversity in Gansu was the highest and that of Beijing was the lowest. The comprehensive analyses indicated that the endophytic fungi of G. uralensis are diverse, and there were differences among the number, composition and population of endophytic fungi in five producing areas of Gansu, Ningxia, Inner Mongolia, Xinjiang and Beijing.

  • Hai-gang WANG, Ling-lei KONG, Rui WANG, Yan-xia CHEN, Shi-lun YANG, Xiao-yue ZHAO, Qi-meng ZHOU, Guan-hua DU
    Acta Pharmaceutica Sinica. 2019, 54(2): 301-307.

    This study was designed to compare the antithrombotic effects of salvianolic acid A and aspirin. The anti-platelet aggregation and anticoagulant effects of salvianolic acid A and aspirin in vitro and in vivo were investigated in normal rats. The anti-cerebral ischemia and anti-platelet aggregation effects of salvianolic acid A and aspirin were also investigated in rats with thrombotic cerebral ischemia. All animal care and experimental procedures were reviewed and approved by the Animal Ethics Committee of Chinese Academy of Medical Sciences. The results of antiplatelet aggregation in vitro and in vivo showed that salvianolic acid A could mildly inhibit adenosine diphosphate (ADP), arachidonic acid (AA) and thrombin (THR)-induced antiplatelet aggregation in a dose-dependent manner, while aspirin played a strong inhibitory effect on AA-induced platelet aggregation in vivo. The effects of salvianolic acid A and aspirin on the coagulation system were similar. At the same time, the results of maximum platelet aggregation rate (MAR) in the rat cerebral ischemia model[MARADP=(41.67±4.55)%, MARAA=(53.22±2.83)%, MARTHR=(73.33±5.04)%] indicated that salvianolic acid A could mildly inhibit ADP and AA-induced antiplatelet aggregation[MARADP=(26.13±4.60)%, MARAA=(35.53±13.73)%, P < 0.01], while aspirin played a strong inhibitory effect on AA-induced platelet aggregation[MARAA=(8.13±2.99)%]. Salvianolic acid A (10 mg·kg-1) significantly improved the neurological function, cerebral infarction volume[(10.77±7.80)%] and brain edema[(79.72±0.83)%] compared with the model group[(43.50±12.69)%, (82.25±0.89)%] (P < 0.01), while the effect of aspirin (100 mg·kg-1) was not obvious. The above results suggest that compared with aspirin, salvianolic acid A provided a mild inhibitory effect on platelet aggregation and protected against cerebral ischemia induced by thrombus. Therefore, salvianolic acid A has a good application prospect in the prevention and treatment of thrombotic diseases.

  • Xue-song LIU, Si-yu ZHANG, Man-qian ZHAO, Jun WANG, Ye-rui LI, Jun DAI, Chuan-zhen TENG, Xiao KE, Yong CHEN, Yong-jiang WU
    Acta Pharmaceutica Sinica. 2019, 54(1): 138-143.

    Near-infrared spectroscopy (NIRS) combined with chemometrics can achieve rapid detection in process analysis. After variable selection, the redundant information is effectively removed and the characteristic variables related to the response values are selected. Compared with global model, the complexity is significantly reduced and the prediction accuracy is also improved. In this study, near-infrared spectroscopy analysis combined with different variable selection methods was applied to achieve the rapid detection of baicalin in the extraction process of Scutellaria baicalensis. Data sets were divided based on sample set portioning based on joint x-y distance (SPXY) method. Competitive adaptive weighted resampling method (CARS), random frog (RF) and successive projections algorithm (SPA) were applied to variable selection. Partial least squares (PLS) models were constructed based on above three methods, and the prediction results were compared. After CARS, RF and SPA method, 92, 10 and 17 variables were screened out respectively. According to the performance of the models, CARS method is found to be more effective and suitable than RF and SPA. Furthermore, the characteristic variables selected by CARS method have a better correspondence with the chemical structure of baicalin. The root mean square error (RMSEC) of the calibration set and the root mean square error (RMSEP) of the prediction set are 0.528 2 and 0.720 2 respectively. Compared with the global PLS model, the correlation coefficient of the calibration set (Rc) is increased to 0.979 9 from 0.917 0, and the relative standard errors of prediction (RSEP) is reduced to 5.59% from 10.58%.