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  • Fang-zhe ZHAO, Xiao-qing SANG, Yan ZHU, Jian YANG
    Acta Pharmaceutica Sinica. 2020, 55(5): 892-897.

    Idiopathic pulmonary fibrosis (IPF) is usually accompanied with inflammatory response, especially the macrophages. The co-culture model of macrophages and fibroblast, and IPF mice model induced by bleomycin were used here to explore the role of macrophages and interleukin-6 (IL-6) in IPF. All animals welfare and experiments were performed following the regulations of the Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine. The results showed that the content of IL-6 in IPF mice induced by bleomycin was significantly increased, and there was a large amount of inflammatory cell infiltration in the lungs. The results of wound-healing and immunofluorescence showed that alternative activated (M2) macrophages could induce the migration and activation of fibroblasts at 36 h, and the expression of IL-6 was increased in the co-culture system. The results of wound-healing and sirius red assay proved that IL-6 could induce the migration and activation of fibroblast. The results showed that M2 macrophages induced fibroblasts to secrete IL-6, thereby inducing the activation and migration of fibroblast, which affect the development of IPF.

  • Li-shan PEI, Xia SHEN, Yong-gang YAN, Gang ZHANG, Liang PENG, Yan-xia WANG, Fan PING
    Acta Pharmaceutica Sinica. 2020, 55(5): 898-906.

    Stroke has been harmful to human health for a long time, and there is no satisfactory treatment strategy because of its complex pathogenesis. Taohechengqi decoction has been effective in the treatment of stroke. In this study, the components were collected by TCMSP, TCMIP, BATMAN-TCM and TCMID databases, the targets were predicted and screened by PharmMapper and BATMAN-TCM databases, and the functional enrichment analysis of the targets was carried out by using R language package clusterProfiler. Finally, the key targets are verified by GEO database and molecular docking. The results showed that 51 active components of Taohechengqi decoction may regulate 15 key targets such as nitric oxide synthase, endothelial (NOS3), prostaglandin G/H synthase 2 (PTGS2), matrix metalloproteinase-9 (MMP9), affecting vascular endothelial growth factor signaling pathway and other pathways to play a role in the prevention of stroke, affecting tumor necrosis factor signaling pathway and other pathways to play a role in the treatment of stroke. GEO data analysis showed that androgen receptor (AR), caspase-8 (CASP8), intercellular adhesion molecule 1 (ICAM1), interleukin-1 beta (IL1B), mitogen-activated protein kinase 14 (MAPK14), MMP9, myeloperoxidase (MPO), peroxisome proliferator-activated receptor gamma (PPARG), PTGS2 and cellular tumor antigen p53 (TP53) were up-regulated genes, while serum albumin (ALB), estrogen receptor 1 (ESR1), NOS3, transcription factor p65 (RELA) and proto-oncogene tyrosine-protein kinase Src (SRC) were down-regulated genes. GEO analysis explained that Taohechengqi decoction may prevent stroke by down-regulating ESR1, NOS3, and treat stroke by up-regulating ICAM1, IL1B, MAPK14, MMP9, PPARG, PTGS2, TP53, and down-regulating RELA and SRC. The study found that in the process of prevention and treatment of stroke, Taohechengqi decoction played a two-way regulation role through multi-genes and multiple ways, which provided a new strategy for the treatment of stroke.

  • Hao FENG, Qian-qian DU, Zhi-qiang FENG, Yan LI, Zhong-cheng LIU, Xiao-ling XU
    Acta Pharmaceutica Sinica. 2020, 55(5): 958-966.

    Hypoxia-activated prodrugs that specifically target tumor tissues were designed by attaching the nitro-aromatic ring carrier molecules that can be degraded in the hypoxic microenvironment of the tumor to the hydroxyamidine group of IDO1 inhibitor compound B and epacadostat. Eleven prodrug compounds were synthesized and their structures were confirmed by 1H NMR and HR-MS. Compounds F-1 and F-6, which had a higher stability and drug release rate, were identified by an in vitro stability assay, nitroreductase reduction assay, MTT assay, and an in vivo tumor tissue hypoxia degradation assay, and then evaluated for anti-tumor efficacy in vivo. The results showed that prodrug F-1 inhibited tumor growth by 67.41%, which was significantly higher than 42.31% for the starting drug group. It appeared that the inhibition of IDO1 in the tumor tissue was different from the overall inhibition of IDO1 in vivo. Animal treatment procedures were carried out with the approval of the Animal Care and Use Committee of the Chinese Academy of Medical Sciences and Peking Union Medical College.

  • Xi WU, Mei JIANG, Hai-mei CHEN, Li-qiang WANG, Lin-fang HUANG, Chang LIU
    Acta Pharmaceutica Sinica. 2020, 55(5): 1042-1049.

    Inula japonica, Inula hupehensis and Inula linaariifolia are all medicinal plants of Inula L. in the Compositae family, and Inula hupehensis is endemic to China. In order to compare their genomic sequence differences and provide scientific basis for their germplasm conservation and development, we obtained and analyzed the complete chloroplast genomes of these three species. Total DNAs were extracted from fresh leaves and subjected to next-generation DNA sequencing. NOVOPlasty was used to assemble the chloroplast genomes from the sequence reads. CPGAVAS2 was used to annotate the genes and repeats in each genome. Lastly, phylogenomics analysis was conducted using RAxML. The results showed that the total length of the chloroplast genome of Inula japonica, Inula hupehensis and Inula linaariifolia is 150 754, 150 909, and 150 812 bp respectively, each consisting of a large single copy region, a small single copy region and a pair of inverted repeat regions. In addition, the G/C content of all three chloroplast genomes was approximately 37.7% and each encoded 111 unique genes, including 79 protein-coding, 28 tRNA and 4 rRNA genes. Meanwhile, 32, 33, 34 simple repeat sequences, 18, 22, 18 tandem repeat sequences and 33, 37, 38 scattered repeat sequences were identified in three species. Phylogenomic analysis showed that all three species of Inula L. and Pluchea indica were clustered together, with the relationship between Inuleae and Senecioneae closer, suggesting that Inuleae may have originated from the Senecioneae, not the Cardueae. The data in this study not only enriches the chloroplast genome database of Inula L., but also lays the foundation for the future studies of species identification, phylogenetic relationships, evolution history and genetic diversity of Inula species.

  • Ting XIONG, Li WU, Hui PENG, Wei QIAN, Wen-ting WU, Wei-feng ZHU, Xian-zhen YIN, Ji-wen ZHANG
    Acta Pharmaceutica Sinica. 2020, 55(5): 1030-1034.

    It is difficult to directly observe the structural transformation inside of soft capsules if their shells are opaque. This study was designed to noninvasively in situ measure the structural characteristics of the soft capsules and internal particle distributions to reveal the intrinsic quality of the soft capsules and develop a new technique for reverse engineering and the physical stability evaluation of the soft capsules. In this research, the CT projection images of soft capsules, namely, propolis soft capsules, were collected via synchrotron radiation X-ray micro computed tomography (SR-μCT). After three-dimensional reconstruction, the structural differences of the soft capsules under long-term test and accelerated test for 6 months were quantitatively analyzed by calculating the three-dimensional structure parameters such as volume, number and distribution of the particles inside and the thickness for the wall of the capsules. There were only a small number of particles evenly distributed in the soft capsules stored under common storage condition without layering. On the other hand, the shell wall of the soft capsule turned thinner locally at the occlusal portion and the particles with strong X-ray absorption were densely distributed at the edge of the capsule wall after the accelerated test. This study revealed that the structural parameters of soft capsules obtained by SR-μCT could be used to evaluate the influence of storage environment on the physical stability of soft capsules. The technology provides a new method for quality control and evaluation for the soft capsules.

  • Yang CHEN, Juan NI, Yun GAO, Zhong-jian CHEN, Yong-jiang WU
    Acta Pharmaceutica Sinica. 2020, 55(5): 987-994.

    To investigate the antitumor activity of shikonin against human colorectal cancer, the IC50 value towards four different human colon cancer cells was detected by MTT assay. In addition, a SW620 xenograft model was established and both the tumor volume and tumor inhibitory rate were calculated to evaluate the antitumor activity of shikonin in vivo. To further explore the mechanism of shikonin, metabolomics combined with multivariate statistical analysis was performed to analyse the profile of metabolites in mouse serum. The results show that shikonin can significantly inhibit the proliferation of four different colon cancer cell lines and exerted a high antitumor activity in vivo. The tumor inhibitory rate at low dose and high dose were 38.35% and 42.16%, respectively. In addition, a total of 38 potential biomarkers related to the antitumor effects of shikonin were identified through metabolomics analysis, including tryptophan, proline and methionine. The study revealed that the mechanism was related to disordered amino acid metabolism in colon cancer, especially in tryptophan metabolism. Our study suggests that shikonin could exert an antitumor effect by regulating amino acid metabolism in colon cancer and provides a theoretical foundation for further exploration and the eventual clinical application of shikonin.

  • Xian-shuang CHEN, Ke LI, Zhen-yu LI, Xue-mei QIN
    Acta Pharmaceutica Sinica. 2020, 55(5): 979-986.

    "Beany flavor" is one of the important authentic characteristics of Astragali Radix. It is important to clarify the material basis of "Beany flavor" in the characterization of authentic medicinal materials and establishing quality control methods for authentic medicinal materials. At present, the analysis of volatile components in different habitats has been reported, but systematic comprehensive research has not been conducted. The SPME-GC-MS technique was used to analyze the volatile components of Astragali Radix from three producing areas:Shanxi (wild-simulated Astragali Radix), Gansu (cultivated Astragali Radix) and Inner Mongolia (cultivated Astragali Radix). Combined with the method of multivariate statistical analysis, the difference of volatile components of Astragali Radix from the three different producing areas is discussed. Multivariate statistical analysis and evaluation was conducted through principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). Seventy-six volatile components of Astragali Radix from the three producing areas were identified by SPME-GC-MS. PCA model results showed that the volatile components correlated with their producing areas. PLS-DA demonstrated that the volatile components of Astragali Radix samples from different producing areas were significantly different. Six volatile substances including hexanoic acid, hexanal, 2-butyl-2-octenal, 1-hexanol, benzyl alcohol and 2-butylfuran were quantified. The ratio of hexanal to hexanoic acid in Astragali Radix from different areas and cultivation methods was significantly different:the ratio of hexanal:hexanoic acid in wild-simulated Astragali Radix of Shanxi was 7.8:1, while the ratio of hexanal:hexanoic acid in cultivated Astragali Radix of Inner Mongolia and Gansu was 2.3:1 and 0.96:1, respectively. The volatile components identified in this study provide a foundation for continued research of and quality control of Astragali Radix.

  • Jin-yue ZHANG, Qi-feng LIU, Liu YANG, Xue-qi LÜ, Ying-hong WANG
    Acta Pharmaceutica Sinica. 2020, 55(5): 832-842.

    Heart failure is the end stage of many cardiovascular diseases. It seriously affects the safety and quality of life of nearly 40 million people worldwide. At present, the clinical and pathophysiological characteristics of some types of heart failure are unknown, and there is no effective diagnosis and treatment. In recent years, genomics, transcriptomics, epigenomics, proteomics, metabolomics and other omics technologies have been widely used in disease research, providing new opportunities for the prevention, diagnosis and treatment of diseases. These strategies have also brought hope for the reduction in heart failure mortality. Based on the current status of clinical treatment of heart failure, this article reviews the roles and potential applications of these various omics technologies and their opportunities in the study of the pathogenesis of heart failure, clinical diagnosis and treatment, and related drug pharmacodynamics and mechanism of action.

  • Xin-yue YANG, Hai-xin LIU, Shuang HE, Rui SHAO, Yu-xin FENG, Yan ZHU
    Acta Pharmaceutica Sinica. 2020, 55(5): 854-860.

    Phytoestrogens exhibit various pharmacological estrogen-like effects, such as in the prevention and treatment of osteoporosis, cardiovascular diseases, tumors, etc., but the specific mechanism is still unclear. In recent years, estrogen receptor alpha-mediated rapid non-genomic effects have been identified to play an important role in the pathogenesis of estrogen-related diseases. The research of phytoestrogens exerting pharmacological effects through non-genomic effects has also received increasing attention. This article summarizes the research progress in estrogen receptor alpha-mediated non-genomic effects and analyzes the possible involvement of rapid non-genomic effects in certain pharmacological effects of phytoestrogens. The future prospects of estrogen receptor-mediated non-genomic effects by phytoestrogens are also discussed.

  • Zhi-peng FU, Zhong-xia ZHOU, Xin-yong LIU, Peng ZHAN
    Acta Pharmaceutica Sinica. 2020, 55(4): 703-719.

    Long-term use of approved antiviral drugs can lead to drug resistance and side effects. On the other hand, there are currently no antiviral drugs or vaccines available to treat some newly emerging virus infections. Therefore, antiviral drugs research has always been a hot research topic in the field of medicinal chemistry. Natural products are an important source of antiviral drugs. This article reviews the progress of antiviral natural products discovered in the past decade to provide potential lead compounds for drug development.