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  • Jing-wen SUN, Guo-guang WEI, Yu-yi QIAN, Bin-bin ZHENG, Shuai GAO, Qing-tong YI, Wei LU
    Acta Pharmaceutica Sinica. 2020, 55(7): 1699-1706.

    The near-infrared-Ⅱb (NIR-Ⅱb, 1 500-1 700 nm) window fluorescence with long emission wavelength has reduced light scattering and tissue auto-fluorescent background, achieving deep tissue imaging with high spatial resolution. Herein, we prepared an NIR-Ⅱb fluorescent quantum dots (QDs) composed of lead sulfide (PbS). The fluorescence spectrum of PbS QDs were adjusted by controlling the size of the PbS core. Cadmium sulfide (CdS) shell was synthesized by the cation exchange method to form the core/shelled lead sulfide/cadmium sulfide quantum dots (CSQDs). The surface of CSQDs was modified with polyethylene glycol (PEG) to increase their stability in aqueous solution. The resulting PEG-modified CSQDs (PEG-CSQDs) had the emission peak at ~1 550 nm with quantum yield of 7.2%. The animal procedures were approved by the Institutional Animal Care and Use Committee (IACUC) of Fudan University School of Pharmacy. At 2 h postinjection, PEG-CSQDs clearly delineated the tumor region of mice bearing orthotopic CT26-Luc colon cancer model in the NIR-Ⅱb fluorescence imaging. The fluorescent intensity ratio of primary tumor and adjacent normal tissue was 42.3, and that of metastatic tumor and adjacent normal tissue was 22.3, which allowed to detect the primary tumor of 3.4 mm×2.5 mm in dimension and the metastatic tumor of 1.2 mm×0.9 mm in dimension, and accurately guided the excision of tumors. The PEG-CSQDs prepared in this study provided a new approach for the early diagnosis and guidance of surgical resection of colon cancer.

  • Sheng-yu YAO, Xing-yan FAN, Kuan JIANG, Yang HU, Gang WEI, Yong GAN, Wei-yue LU
    Acta Pharmaceutica Sinica. 2020, 55(7): 1549-1561.

    Diabetes is characterized by hyperglycemia, resulting from insulin deficiency or resistance, or both. Insulin plays an irreplaceable role in the treatment of diabetes. Subcutaneous injection is the main route of insulin administration, but usually leads to poor compliance and many side effects. Oral insulin is safer and more convenient, which has always been the Holy Grail for people to explore. After oral administration, insulin is absorbed into the hepatic portal vein and transported to the liver, which can activate the normal physiological functions and reduce the risk of hypoglycemia, insulin resistance, and improve patient compliance. However, the gastrointestinal tract has multiple absorption barriers such as chemical barrier, enzyme barrier, and permeation barrier. Due to the physical and chemical properties of insulin, it is difficult to achieve desired oral bioavailability. This article reviews the recent attempts and progress in the field of oral administration of insulin driven by innovative drug delivery technologies and biomaterials, including structural modification, enzyme inhibitors, absorption enhancers, various nanoparticles, liposomes, microspheres, and even microorganisms. Some clinical researches on oral insulin are also introduced.

  • Pan YAN, Shuai-long JIA, Sen LI, Zhi-feng DU, Hong-liang JIANG
    Acta Pharmaceutica Sinica. 2020, 55(7): 1494-1503.

    Traditional Chinese medicine (TCM) has made numerous contributions to the prosperity of China. However, the phytochemicals of TCM are complex, and there are significant differences in relative content. The material basis of TCM has restricted the modernization of TCM. Liquid chromatography-mass spectrometry (LCMS) combines the high separation performance of chromatography and the high sensitivity of mass spectrometry. It has been widely used in the analysis of natural medicines and can greatly promote the development of TCM. Many studies have focused on the comprehensive characterization of phytochemicals, building a strategy for the rapid, accurate and systematic analysis of the chemical components of TCM through the integration of different mass spectrometric techniques, and laying the foundation for quality control and rational utilization of TCM.

  • Sheng-jie YE, Kai-li HU
    Acta Pharmaceutica Sinica. 2020, 55(7): 1540-1548.

    Exosomes are disk-shaped vesicles with a diameter of 40-100 nm, which are composed of natural lipid bilayers. Most cells can produce exosomes, which play an important role in physiological and pathological processes, affecting signal pathways, intercellular communication, tumor progression and molecular metastasis. Exosomes are characterized by low immunogenicity, good natural stability, long half-life, high delivery efficiency, and the ability to cross the blood-brain barrier, which can be used as a good carrier for drug delivery. This review focuses on the research progress of exosomes as drug delivery systems in the treatment of brain diseases, such as central nervous system degenerative diseases, brain tumors and cerebrovascular diseases and so on.

  • Huai-song WANG, Ya DING
    Acta Pharmaceutica Sinica. 2020, 55(7): 1511-1519.

    Metal-organic frameworks (MOFs) are porous crystalline polymers constructed from the coordination reaction between organic ligands and metal ions. Due to their advantages:adjustable periodic pore structure, large specific surface area and easy functional modification, etc., MOFs have been widely used in the fields of gas storage/separation, catalysis, sensing, biological imaging and drug delivery. In recent years, MOFs have shown great potential in disease diagnosis and treatment. This review summarizes the application of MOFs in the fields of bio-sensing, cell imaging, in vivo imaging, drug delivery, etc., discusses the problems and corresponding solutions in the application of MOFs for biomedicine. We hope this review can provide reference for the designing new methods for disease diagnosis and treatment.

  • Ying MA, Yuan CAI, Xiao-jing MA, Guang-hong CUI, Jin-fu TANG, Wen ZENG, Shui-han ZHANG, Juan GUO, Lu-qi HUANG
    Acta Pharmaceutica Sinica. 2020, 55(7): 1573-1589.

    Most of the active ingredients of herbs are secondary metabolites of plants. Cytochrome P450s (P450s) are hemoglobin-containing monooxygenases encoded by a super-gene family, which play important roles in the metabolic network of plants. This review focuses on the role of P450s on biosynthesis of secondary metabolites such as terpenoids, alkaloids, flavonoids and phenylpropanoids. This will provide references for biosynthesis and regulation of secondary metabolites in medicinal plants.

  • Ting-ting XU, Peng GUO, Wei ZHANG, Xiao-liang WANG
    Acta Pharmaceutica Sinica. 2020, 55(7): 1604-1613.

    To identify potential serum proteins that might serve as biomarkers for Alzheimer's disease (AD), we performed comparative proteomic profiling of sera from AD and healthy control subjects using label-free LC-MS/MS. Our study identified 387 proteins, 61 of which showed significant changes in the serum of AD patients compared to healthy controls. Gene ontology (GO) enrichment analysis showed that some GO terms related to the pathogenesis of AD were significantly enriched in differentially expressed proteins, including cholesterol and lipid metabolism, inflammation, coagulation and hemostasis processes, and immune responses. Therefore, based on the above results and the consistency of protein content changes in the 8 comparison groups, 18 proteins were selected as candidate biomarkers. Protein-protein interaction results suggest that these 18 proteins can directly or indirectly interact with APP. Therefore, changes in the levels or functions of these proteins may affect Aβ metabolism and participate in the occurrence of AD, and have the potential to become AD blood biomarkers.

  • Xue-ning WANG, Jian-qiang KONG
    Acta Pharmaceutica Sinica. 2020, 55(7): 1590-1603.

    Puerarin, also known as daidzein 8-C-glucoside, is a major isoflavone glycoside from Pueraria lobata. Puerarin has been shown to possess a variety of pharmacological activities. It has been widely used for the treatment of cardiovascular and cerebrovascular diseases. However, the further applications are limited due to its low water solubility and poor bioavailability. Structural modification is thus regarded as an efficient approach to improve the solubility and bioavailability of puerarin. Unlike chemical modifications, enzyme-assisted modifications, namely biocatalysis, is a promising alternative for the regioselective synthesis of puerarin derivatives due to its high selectivity. Up to date, acylation, glycosylation and hydroxylation of puerarin had been achieved through enzyme-based biocatalysis. Diverse active puerarin derivatives with improved solubility and bioavailability have been thus developed. Based on modification groups, this paper focused on the progress in the preparation of puerarin derivatives by biocatalysis, in which the whole-cells or pure enzymes were used as the biocatalysts. This article was expected to provide new ideas for the synthesis and development of puerarin drugs.

  • Miao-jie WEI, Jin-xin LIU, Qing ZHAO, Xiao-lan XU, Ping REN, Ming-yue LI, Lin-chun SHI, Wei SUN
    Acta Pharmaceutica Sinica. 2020, 55(6): 1327-1333.

    This study aimed to establish a method for identification of the prescription components of Pule'an Tablet based on DNA barcoding technology. Sixteen samples have been collected from 8 different companies, and their DNA were purified using Plant and Animal Genomic Kits. The amplification rates of ITS2 were both 100%, and the amplification rates of COI were 43.75% and 56.25% for these samples' DNA purified using plant and animal kits, respectively. For ITS2, 12 samples obtained high-quality sequencing traces and then were identified as containing Brassica campestris. The other 4 samples showed crucial SNP peaks in the sequencing traces, which were assigned to be B. campestris and B. nigra on the basis of cloning and sequencing experiments. For the PCR products of 9 samples from COI universal primers, two samples were directly sequenced and identified as aphids, and 7 other samples were subjected to cloning and sequencing experiments. Finally, we obtained 82 clone sequences and found that Apis mellifera was detected only in 5 of the remaining 7 samples, and pathogens or pests were detected in all these 7 samples. To solve the failure of bee source detection caused by exogenous contaminations based on COI universal primers, we designed two new COI primer pairs of Apis genus. The amplification rates of both primer pairs were 43.75%, and they were identified as A. mellifera. A total of 9 bee source-free Pule'an Tablet samples from 3 different batches were produced by the same company, and each batch contained 3 replicates. Thus, we speculated that raw rape pollen materials for these 9 samples was not collected by bees. This study proposes an identification method for the prescription components of Pule'an Tablets based on ITS2 and COI sequences, which will provide scientific basis and technical guidance for quality control and market regulation of Pule'an Tablets.

  • Ji-hong YAO, Jing WANG, Zi-qi HU, Luan SHU
    Acta Pharmaceutica Sinica. 2020, 55(6): 1209-1213.

    Our previous report demonstrated puerarin protected β cells by up-regulating the expression of glucagon-like peptide-1 (GLP-1) receptor (GLP-1R). However, whether the anti-diabetic effects of puerarin in vivo depend on GLP-1R activation has not been clarified. In this study, the GLP-1R agonist exendin-4 (Ex4) and the GLP-1R antagonist exendin 9-39 (Ex9-30) were used. Type 2 diabetes was induced in C57BL/6J mice by a high fat diet (HFD) and divided into the following groups: control, HFD, HFD/puerarin (300 mg·kg-1·d-1), HFD/puerarin/exendin 9-39 (Ex9-39: 10 nmol·kg-1·d-1), and HFD/puerarin/exendin-4 group (Ex4: 10 nmol·kg-1·d-1). 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 (AEWC-025). Puerarin was administered orally, Ex9-39 and Ex4 were administered by intraperitoneal injection for 10 days. Compared with HFD group, after 10-day treatment, the fasting blood glucose and oral glucose tolerance test (OGTT) of diabetic mice were effectively improved by puerarin (P < 0.05). Meanwhile, serum insulin levels were increased by puerarin, and levels of glucagon, triglycerides, and total cholesterol were significantly reduced (P < 0.05). Importantly, Ex4 significantly enhanced the anti-diabetic effects of puerarin in HFD mice, while Ex9-39 markedly inhibited the effects of puerarin (P < 0.05), which indicates that the effects of puerarin depend on GLP-1R activation. Furthermore, results of Western blotting of liver tissue showed puerarin effectively activated AKT and inhibited FOXO1, which relied on GLP-1R activation as well. Taken together, our findings demonstrate that puerarin ameliorates glucose homeostasis in HFD mice and is dependent on GLP-1R activation. This study provides experimental support for the potential application of puerarin.