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  • Xian-sheng MENG, Yong-rui BAO, Shuai WANG, Tian-jiao LI, Guo-an LUO
    Acta Pharmaceutica Sinica. 2019, 54(2): 222-227.

    The chemical composition of traditional Chinese medicine (TCM) compounds is complex, the treatment is broad, and the quality control indexes cannot accurately reflect the functional properties. According to the above problems, the authors take the research process of quality markers of Qizhiweitong granules as an example to innovate the research ideas and technical methods, and constructed five progressive steps of TCM compounds quality control and evaluation model:"based on function, to figure out the attending", "components and pharmacodynamics correlation, multiple components with multiple effects", "to analyze the components, and systematically integrate them", "spectrum and effect correlation, from a spectrum to see the efficiency", and "from the content-effect colour atla to see the quality". Based on the multiple effects of components, multiple components of multi-effect pharmacological efficacy evaluation system were established. All-time isobaric multiwavelength fusion fingerprint technology was improved and developed. "Spectrum-effect colour atla" software was research and developed for the first time, to realize the "visualization" of TCM efficacy. The aim of this work is to provide an exploratory solution for the integrated quality control of TCM compounds.

  • Yi-xiu ZHAO, Xue LIU, Yan ZHANG
    Acta Pharmaceutica Sinica. 2019, 54(2): 228-234.

    Atherosclerosis refers to vascular pathological changes in which vascular lumen was narrowed or blocked by cholesterol or fat existed in vascular endothelium, which could induce serious cardiovascular events. The pathogenesis of atherosclerosis is complicated extremely. Vascular endothelial dysfunction initiated the plague formation and deterioration, which determined the prognosis of atherosclerosis. Circular RNA (circRNA) is a special endogenous non-coding RNA, which has become a research hotpot in the field of non-coding RNA. This review aims to bring together the recent research on the pathogenesis and pathological process of endothelial dysfunction, and the regulative effect of circRNA on it. Our article will provide new targets and new ideas for the research and development of anti-atherosclerosis drugs.

  • 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.

  • Jian-ping CAO, Yong-xiao MOU, Yuan-yuan CHEN, Tao WEI, Chao-jie WANG
    Acta Pharmaceutica Sinica. 2019, 54(2): 245-257.

    Ionic liquids are not limited to the traditional use of solvents because of their high permeability and excellent physicochemical and unique biological properties. Nowadays, with the deep understanding of their toxicity and biocompatibility, ionic liquids have been tailored as novel solutions to address potential problems of marketed drugs. Based on the research and development of modified new drugs, ionic liquids have been incorporated into drug synthesis and emerged as attractive environmental-friendly reaction media with milder reaction conditions, higher yields and easier reaction workups and drug delivery systems. In addition, they have been designed for effective drug carriers removing undesirable properties of solid drugs. Further, ionic liquids forming active pharmaceutical ingredients dedicated to the liquefaction of drugs for promising clinical applications.

  • 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.

  • Ying CAI, Yang CHEN, Wen-ting ZHOU, Yue-hua LIAO, Zhan-ying HONG, Yi-feng CHAI
    Acta Pharmaceutica Sinica. 2019, 54(2): 269-280.

    The blood-brain barrier (BBB) not only maintains the stability of the environment within the central nervous system by controlling the transport of substances on both sides of the blood and brain, but also plays an important role in the R&D of new drugs for neurological disorders. The establishment of an in vitro high-fidelity model to study BBB function is imperative for assessing barrier permeability of drugs and xenobiotics. However, the complexity of the BBB structure makes it difficult to replicate with an in vitro model. Compared to the traditional in vitro BBB model, the BBB-on-chip provides certain advantages in miniaturizing the system, reducing the amount of cells and medium required, and allowing simultaneously induction of shear stress. We review here the BBB-on-chip models from their establishment and characterization to applications in research of neuroinflammation, brain tumor and drug evaluation.

  • Li-ping XIANG, Li CONG, Yong ZHANG, Su-juan LIU, Xiao-lin XIE, Ping-juan BO, Xue-ping XIANG, Xiao-hua FU
    Acta Pharmaceutica Sinica. 2019, 54(2): 281-287.

    The research is aimed to investigate the effect of genistein (GEN) on the apoptosis in lipopolysaccharide (LPS)-activated RAW264.7 cells and explore the pharmacological mechanism of GEN anti-atherosclerosis (AS). RAW264.7 cells were activated by LPS, the level of TNF-α and IL-6 mRNA were detected by qRT-PCR, the expression of COX-2 and iNOS were detected by Western blot. RAW264.7 cells were pretreated with GEN for 2 h, and then incubated with LPS for 24 h. After that, CCK8 kit was used for the cell viability, Annexin V-FITC/PI kit for the apoptosis of cell. qRT-PCR was used to detect the level of CHOP, caspase-3 and miR-21. Western blot was used to detect the expression of CHOP and caspase-3. Results showed that LPS (1 000 ng·mL-1) increased the expression of TNF-α, IL-6, COX-2 and iNOS in RAW264.7 cells compared with that in control group. GEN inhibited the cell activity and the level of miR-21, promoted the expression of CHOP and caspase-3 in LPS-activated RAW264.7 cells in a dose-dependent manner. miR-21 up inhibited the expression of CHOP and caspase-3 in LPS-activated RAW264.7 cells and this process was reversed by GEN treatment. miR-21 down promoted the expression of CHOP and caspase-3, which were further enhanced by GEN. These results indicate that GEN promotes the apoptosis of RAW264.7 cells activated by LPS through down regulating miR-21 and activating endoplasmic reticulum (ER) stress pathway.

  • Jia-li WANG, Ji-hong YAO, Qing NING, Hong-xue SHEN, Zhen-hai ZHANG, Luan SHU
    Acta Pharmaceutica Sinica. 2019, 54(2): 288-293.

    To investigate the potential hypoglycemic effect of nanosuspensions of honokiol and explore the underlying mechanisms, a high fat diet (HFD) was studied in C57BL/6J mice divided into five groups:normal diet (ND), HFD, HFD/honokiol-sodium carboxymethyl cellulose (CMC-Na) (Hono-CMC, 100 mg·kg-1), HFD/honokiol-Nano (Hono-Nano, 80 mg·kg-1), HFD/metformin (HFD/Met, 200 mg·kg-1). Fasting blood glucose (FBG) and body weights (BW) of mice were measured every seven days. After 30-day treatment, an oral glucose tolerance test (OGTT) was performed, and blood and tissue samples were collected for analysis. All animal experiments were approved by the Research Animal Care Committee of Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine. The data showed Hono-Nano and metformin reduced FBG, BW, and markedly improved OGTT of mice compared to HFD group (P < 0.05). Hono-CMC produced nonsignificant impact on FBG, BW of mice, while OGTT of mice was improved by Hono-CMC (P < 0.05). Meanwhile, none of these treated groups showed significant effects on regulating serum insulin levels, but all of them exhibited decreased serum glucagon levels notably compared to the HFD group (P < 0.05). Western blot analysis revealed that honokiol up-regulated levels of p-AMPK and p-FOXO1 in liver tissue of HFD mice (P < 0.05), which resulted in activation of AMPK and inhibition of FOXO1. Moreover, the expression of PEPCK (a key enzyme of gluconeogenesis) was decreased by honokiol (P < 0.05). Taken together, our findings demonstrate that nanosuspension of honokiol is more effective than CMC-Na-suspension of honokiol on blood glucose controlling in HFD mice. The hypoglycemic effects of honokiol might rely on suppressing hepatic gluconeogenesis via activating AMPK and inhibiting FOXO1.

  • Rong-chang CHEN, Xiao-yu MA, Li-jiao XU, Gui-bo SUN, Xiao-bo SUN
    Acta Pharmaceutica Sinica. 2019, 54(2): 294-300.

    To investigate the effect of scutellarin (Scu) on diabetic cardiomyopathy in mice, type 2 diabetes mellitus was induced by intraperitoneal injection of 50 mg·kg-1 streptozotocin (STZ) into a high-fat diet. Scu was injected intraperitoneally. After 8 weeks, fasting blood glucose and serum biochemical parameters were measured. Masson staining was performed on myocardial tissue. The expression levels of Nrf2, NFκB, AKT and p-AKT in myocardium of mice were observed by Western blot. All the procedures were approved by the Laboratory Animal Ethics Committee of the Peking Union Medical College. The results showed that Scu significantly decreased the heart-body ratio, increased myocardial contractile function, decreased the level of myocardial fibrosis and the expression of collagen I and collagen Ⅲ in myocardium of diabetic mice. Scu can effectively reduce the levels of lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB), malondialdehyde (MDA) in serum of diabetic mice, increase the level of antioxidant enzymes in serum, and inhibit the release of inflammatory factors. Further studies showed that Scu significantly increased Nrf2 nuclear translocation, inhibited NFκB nuclear translocation and increased AKT phosphorylation. It indicates that Scu has significant effect on diabetic cardiomyopathy in mice.

  • 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.