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  • Lu-ming YANG, Hu-biao CHEN, Qiao-ru GUO, Bolati Makabili, Wen-min ZHOU, Pei-min HUANG, Zeng-bao WU, Jian-ye ZHANG
    Acta Pharmaceutica Sinica. 2020, 55(7): 1466-1477.

    Snow lotus is a medicinal plant with a wide range of pharmacological activities. It has been used to treat rheumatoid arthritis, cough with cold, stomach ache, dysmenorrhea, and altitude sickness in traditional medicine. This review summarizes the bioactive components in six species of snow lotus including flavonoids, lignans, phenolic compounds, phenylpropanoids, and sesquiterpenes present in Saussurea involucrate (SI), Saussurea obvallata (SO), Saussurea laniceps (SL), Saussurea medusa (SM), Saussurea stella (SS) and Saussurea tridactyla (ST). We review the pharmacological and related molecular mechanisms by which these components exert antineoplastic, anti-inflammatory, and antioxidant effects and promote lipid catabolism, and provide a reference for the future study of the traditional Chinese medicinal chemistry and pharmacological activities of snow lotus.

  • Wen-min ZHOU, Qiao-ru GUO, Hui WANG, Zeng-bao WU, Jian-ye ZHANG
    Acta Pharmaceutica Sinica. 2020, 55(7): 1410-1418.

    The incidence and mortality of chronic obstructive pulmonary disease (COPD) and lung cancer are increasing year by year, which are causing massive social and financial burdens around the world. An increasing number of investigations indicate the possibility of COPD transforming into lung cancer. The pathogenesis of these two diseases have some common aspects, such as epithelial-mesenchymal transition, chronic inflammation, DNA damage, impaired immune system, oxidative stress and tumor angiogenesis, which are heavily complicated. This review summarizes the epidemiological connection between COPD and lung cancer, the molecular-level transformation mechanism as well as the therapeutic strategy. Exploring the transformation mechanism and related signaling pathway of COPD to lung cancer can contribute to block the risk factors for the transformation and provide guidance for the novel drug development and drug therapy.

  • Nan AN, Zi-qi CHEN, Min HUANG
    Acta Pharmaceutica Sinica. 2020, 55(7): 1373-1381.

    Vascular endothelial cells play a major role in maintaining the oxygen and nutrient supply to all tissues in the body. Endothelial cells, together with vascular endothelial growth factor, are also the driving forces of tumor angiogenesis, a process describing the growth of blood vessels from the existing vasculature in tumor tissues. Reprogramming of endothelial cell metabolism satisfied the needs for biomass and energy in the process of tumor angiogenesis, which are known to involve the aspects of glucose metabolism, amino acid metabolism, and fatty acid metabolism. Recently, with the increasing interest to understand the metabolic regulation in cancer, the investigation into the metabolism of endothelial cells has made progress. We herein review the role of endothelial cell metabolism in angiogenesis, with a particular focus on the metabolic regulation of endothelial cells in tumor angiogenesis, which hopes to provide insights for the intervention of tumor angiogenesis in cancer therapy.

  • Yu-yu ZHU, Cheng-lin SONG, Yang SUN
    Acta Pharmaceutica Sinica. 2020, 55(7): 1393-1400.

    Psoriasis, bringing great trouble to patients' life, is a common chronic immune skin disease which is relapsed and difficult to cure. Further understanding of the pathogenesis of psoriasis will be benefit for potential drug targets and the development of therapeutic drugs. In recent years, "interleukin-23/T helper17 (IL-23/Th17) cell axis" has attracted more and more attention in the pathogenesis of psoriasis. Some drugs targeting the cell axis have also been successfully listed in the market to improve psoriasis and achieved good results. This review focuses on the "IL-23/Th17 cell axis" system to elaborate the role of a variety of immune cells involved in the pathogenesis of psoriasis, such as dendritic cells, macrophages, neutrophils and T cells, and summarizes multiple therapeutic antibodies targeting this cell axis in the treatment of psoriasis. In addition, this review also summarizes the current small molecule drugs for the treatment of psoriasis.

  • Wan-zhen YANG, Jie TU, Na LIU, Chun-quan SHENG
    Acta Pharmaceutica Sinica. 2020, 55(7): 1431-1438.

    Autophagy is a widespread and unique degradation process in eukaryotic cells. When cells are under various stress conditions such as nutritional deficiencies, growth factor deficiencies or hypoxia, autophagy will be initiated to maintain the stability of the internal environment and ensure normal proliferation and differentiation. At present, research on autophagy-related targets is mostly focused on tumor cells. In contrast, research on fungal autophagy targets is still limited. Autophagy plays an important role in growth, development and morphological changes of fungal cells, suggesting that research on fungal autophagy as a drug target should be useful. This article reviews the signal regulation and detection strategies for autophagy in fungal cells, and provides a research basis for the screening of antifungal drugs targeting autophagy-related proteins.

  • Heng-cai YU, Shao-cong HOU, Bing CUI, Ping-ping LI
    Acta Pharmaceutica Sinica. 2020, 55(7): 1419-1430.

    Bile acids (BAs) are increasingly being appreciated as signaling molecules. Studies have shown that BAs regulate glucose and lipid metabolism mainly through the intracellular nuclear receptor farnesoid X receptor (FXR) and the transmembrane G protein-coupled receptor 5 (TGR5). FXR and TGR5 are highly expressed in the intestine. This article summarizes the synthesis, circulation, and regulation of BAs, as well as the effects of BAs on glycolipid metabolism through activation of liver FXR and inhibition or activation of intestinal FXR and TGR5. Furthermore, we illustrate the molecular mechanism of BAs on glycolipid metabolism by the relevant signaling pathways, including small heterodimer partner (SHP), fibroblast growth factor 15/19 (FGF15/19), ceramide and glucagon like peptide-1 (GLP-1). This review may serve as a reference for basic and clinical studies.

  • Rong SI, Ming-han CHENG, Jian GAO
    Acta Pharmaceutica Sinica. 2020, 55(7): 1401-1409.

    Galectin-3 is an endogenous β-galactoside-binding lectin widely distributed in the human body, and it plays an important role in various functions such as cell proliferation, differentiation, apoptosis, cell adhesion, immune response and signal transduction. Accumulating evidence has shown that galectin-3 is involved in the occurrence and development of respiratory diseases, including idiopathic pulmonary fibrosis, lung cancer, pulmonary hypertension and bronchial asthma. This review summarizes and analyzes the research progress on galectin-3 in the above respiratory diseases in order to clarify its role and mechanism, and to provide new ideas for clinical treatment.

  • Li-fang HUO, Zhan-feng JIA, Wei ZHANG
    Acta Pharmaceutica Sinica. 2020, 55(7): 1364-1372.

    Hypertension is the most common cardiovascular disease. In recent years, reduced baroreceptor activity has been suggested as a main cause of hypertension. The cell body of the primary afferent nerve of the baroreceptor is located in the nodose ganglion (NG). The ion channels and receptors in the NG can affect baroreceptor sensitivity and neuronal excitability, thus regulating blood pressure. This review focuses on recent research progress on ion channels, receptors and other proteins in NG neurons that are involved in modulating the sensitivity of the baroreceptor reflex to regulate blood pressure.

  • Xue FENG, Yu-zhi ZHOU, Jian-xin CHAI, Qiang CHEN, Li GAO, Guan-hua DU, Xue-mei QIN
    Acta Pharmaceutica Sinica. 2020, 55(6): 1214-1221.

    The paper aims to study and compare the effects of Scutellaria baicalensis leaves (SLE) and Scutellaria baicalensis tea (STE) water extracts on the lifespan of Drosophila melanogaster, and explore their anti-aging mechanism through metabolomics. Lifespan, food intake and fertility were measured after administering different doses of SLE and STE to a Drosophila natural aging model, and the metabolic profile of Drosophila was analyzed by metabolomics and multivariate statistical methods. The results showed that SLE and STE (1, 3 g·L-1) could significantly prolong the average lifespan, median life and maximum lifespan of male Drosophila, improve the fertility of Drosophila, and had no effect on the food intake. Through metabolomics technology, 14 differential metabolites related to aging were found, involving a total of five metabolic pathways. All differential metabolites were reversed after STE intervention, while 13 differential metabolites were reversed after SLE intervention. The results suggest that SLE and STE can delay aging of Drosophila, and the anti-aging mechanism is related to energy metabolism.

  • Zong-ru GUO
    Acta Pharmaceutica Sinica. 2020, 55(6): 1098-1109.

    Small molecular drugs with large ring structure have recently attracted the attention in medicinal chemistry, the reason is their advantages in improving pharmacological activity and selectivity, and in satisfying drug-like properties. The macrocyclic structure takes into account both the microscopic structure for binding to targets and the macroscopic properties required by the pharmacokinetics. Although macrocyclic drugs historically originated from natural products, in recent years, they have been successfully designed, expanded the chemical space of traditional small molecules, and, to some extent, broken through the well-known the Role of Five in drug innovation. In addition, macrocyclic molecules also pave the path for developing drugs for non-druggability targets and for interfering with protein-protein interaction. This article focuses on the molecular design of macrocyclic drugs with some successful examples, concisely discusses structural optimization of a few macrocyclic natural drugs, and briefly describes stapled peptides in medicinal chemistry.