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  • Bin ZHANG, Guo-ping ZENG, Xiao-qin XIONG, Qiao-qiao ZHOU
    Acta Pharmaceutica Sinica. 2021, 56(10): 2830-2834.

    Five compounds were isolated from an ethanol extract of Artemisia deversa Diels by solvent extraction, Diaion HP-20, CHP20/P120 MCI, Sephadex LH-20, silica gel and preparative high performance liquid chromatography. Their structures were elucidated by MS, NMR and X-ray as artemideversal (1), 7-hydroxy-6-methoxycoumarin (2), 6, 7-dimethoxycoumarin (3), caffeic acid (4) and 4', 5, 7-trihydroxy flavone (5). Compound 1 is a new eudesmane-type sesquiterpene. In vitro cytotoxic activities of the five compounds were explored by MTT testing with HepG2, A549, HeLa and MRC-5 cell lines. Results show that compounds 1 and 5 significantly inhibited cellular proliferation. The IC50 of compound 1 in A549 and HepG2 cells was 8.36 and 16.51 μmol·L-1; the IC50 of compound 5 in A549 and HepG2 cells was 17.06 and 7.95 μmol·L-1.

  • Lang DING, Xin ZHANG, Qin-ying LI, Chen WANG, Qing-sen SHANG, Chao CAI, Guo-yun LI, Guang-li YU
    Acta Pharmaceutica Sinica. 2021, 56(10): 2841-2848.

    Type 2 diabetes is a common form of diabetes and can have serious consequences for diabetics when their wounds do not heal properly due to impaired function. Glycosaminoglycans (GAGs) are widely found in skin tissue. Due to the isomerization of C6 in uronic acid and different sulfuric acid substitutions, the structure of GAGs is relatively complex. The fine structure of GAGs in the skin of diabetic patients has not been studied. In this study, the structure of GAGs in the skin of streptozotocin (STZ)-induced diabetic mice was characterized by liquid chromatographytandem mass spectrometry (LC-MS/MS). All animal experiments were carried out with approval of the Animal Ethics Committee of Ocean University of China. The results indicate that the content of hyaluronic acid (HA) in STZ-induced diabetic mouse skin was significantly lower than that of non-diabetic mice. Although there was no significant difference in the content of chondroitin sulfate (CS) and heparin sulfate (HS) between diabetic mouse and normal mouse skin, the disaccharide compositions were different. The expression of CS-4S6S, HS-0S, HS-NS, and HS-6S in STZ-induced diabetic mouse skin was higher than in non-diabetic mice. While the content of HS-NS6S was lower. In addition, the degree of sulfation of HS in STZ-induced mouse skin was lower than that of normal mouse skin. These results provide a basis for the pathogenesis of diabetes and the development of wound healing dressings for diabetic patients.

  • Dan WU, Cong CHEN, Chang-hao LIU, Hong-liang WEN
    Acta Pharmaceutica Sinica. 2021, 56(10): 2769-2778.

    Cancer is a malignant disease threatening human health and life. Early diagnosis of carcinoma plays an important role in the treatment of carcinoma, so tumor imaging agents have been the focus of research in this field. Mannose receptor is a C-type lectin receptor, which expressed in various tumor tissues, sentinel lymph nodes and has become an important tumor marker. In recent years, a variety of imaging agents targeting mannose receptors have been designed and developed. This review summarizes the representative achievements.

  • Xin-tong MA, Mei-hua ZHU, Nan WANG, Xin-yue ZHANG, Qing-yu ZHANG, Yu-fei WANG, Yu-ying HOU, Zhi-ling LI, Na YAO, Xiu-ming LIU
    Acta Pharmaceutica Sinica. 2021, 56(10): 2858-2866.

    Flavanone 3-hydroxylase (F3H), flavonol synthase (FLS) and anthocyanin synthase (ANS) are members of the 2-oxoglutarate-dependent oxygenase (2-ODD) superfamily, which play important functions in plant flavonoid biosynthesis. In this study, 16 2-ODD genes involved in flavonoid biosynthesis pathway were screened and identified from safflower genome database using bioinformatics method. The length of the proteins encoded by these genes ranged from 283 (CtFLS2) to 442 aa (CtANS6), and the molecular weight ranged from 32 062.05 (CtFLS2) to 48 245.49 Da (CtANS6). The proteins encoded by these genes were hydrophilic. Phylogeny divided it into three subfamilies, two conserved residues, H-x-D-xn-H and R-x-S, were found in this gene family using conserved motifs analysis, the analysis of cis-acting elements in the upstream 2 000 bp region showed that these genes might be regulated by environmental factors such as light, temperature and plant hormones such as salicylic acid, methyl jasmonate and so on. The members of the safflower 2-ODD gene family involved in flavonoid biosynthesis pathway were analyzed by qRT-PCR, the result showed that the expression patterns of these members were different in diverse flowering period and leaf. This study can lay a foundation for further exploring the function of 2-ODD genes involved in flavonoid biosynthesis pathway in safflower.

  • Yuan-ya ZHANG, Zhi-jun ZHANG, Rui-rong YE, Rong-tao LI
    Acta Pharmaceutica Sinica. 2021, 56(10): 2825-2829.

    Twenty-five quinolizidine alkaloids (including matrine-type 1-14, sparteine-type 15-17, cytisine-type 18-23, other types 24 and 25) were isolated from the roots and rhizomes of Sophora tonkinensis by various chromatographic methods. Their structures were elucidated by physicochemical properties, NMR and MS spectral data. Among them, 12-(1-acetoxyethyl)-cytisine (23) is a new alkaloid derivative, and compounds 13, 16, 17, 24 were isolated from the roots and rhizomes of S. tonkinensis for the first time. Compounds 1, 6, 19 and 20 showed potent inhibitory activity against LPS-induced NO production in RAW 264.7 macrophages, with IC50 values of 39.86 ±0.65, 23.66 ±0.37, 34.56 ±0.45, 47.68 ±0.58 μmol·L-1, respectively.

  • Yu-jie MA, Sheng-lan YU, Qin-qin LI, Lu-yao HUANG, Li YANG, Zheng-tao WANG, Li-li DING
    Acta Pharmaceutica Sinica. 2021, 56(10): 2802-2808.

    In recent years, the prevalence of non-alcoholic fatty liver disease (NAFLD) has been dramatically increased in China and specific targeted therapy is still unavailable. The purpose of this research was to investigate whether schisandrin B (SchB) improves NAFLD and the potential mechanisms. Wildtype mice with C57BL/6J background were treated with special high fat diet (containing 40% fat, 22% fructose, 10% sucrose, and 2% cholesterol) for 16 weeks to induce NAFLD. Then SchB (120 mg·kg-1) were used to treat NAFLD mice for 6 weeks. Body weight, food intake, glucose tolerance, insulin resistance, serum level of total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were assayed and histopathological analysis were performed to evaluate the improvement of NAFLD induced by SchB. Furthermore, the level of lipopolysaccharide (LPS) in serum, intestinal permeability, and the expression of genes and proteins associated with mucosal defense were evaluated, intestinal flora composition in fresh cecal contents were analyzed and differential flora were identified to explore the potential mechanism. All animal experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine. These results showed that SchB significantly reduced the body weight of NAFLD mice without changing food intake, and effectively reduced serum level of TC, ALT, and AST. SchB also significantly altered the composition of the microflora in NAFLD mice, increased the abundance of the Akkermansia muciniphila (A. Muciniphila) and elevated the expression of genes and proteins associated with the mucosal defense in ileum and colon, restored the permeability of intestinal barrier. In summary, SchB improves NAFLD by regulating the composition of the microflora and enhancing the function of intestinal barrier to further reduce the excessive lipids accumulation and hepatic inflammation.

  • Shuai-shuai FAN, Hai-bo REN, Meng-ting YANG, Xin-guo WANG, Li-ying NIU
    Acta Pharmaceutica Sinica. 2021, 56(10): 2835-2840.

    An ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established for the simultaneous determination of seven components (chlorogenic acid, rutin, narirutin, hesperidin, sinensetin, nobiletin, tangeretin) in Citri Exocarpium Rubrum. The separation was performed over 12.0 min on a Shim-pack GIST C18 column (100 mm×2.1 mm, 2.0 μm) with a mobile phase consisting of acetonitrile (A) and 0.1% formic acid water solution (B) with gradient elution at a flow rate of 0.4 mL·min-1; the column temperature was 30℃ and the injection volume was 1 μL. Detection was performed on a QTRAP 4500 mass spectrometer equipped with electrospray ionization. Positive and negative electrospray ionization was performed in multiple reaction monitoring mode. All of the analytes showed good linearity (r ≥ 0.997 3) in the tested ranges, with good precision, repeatability and stability for all analytes. The average recoveries were in the range of 99.32%-107.75% with relative standard deviations RSD ≤ 3.94%. The established method is accurate, stable and reproducible, and can provide a research method for the quality control of Citri Exocarpium Rubrum.

  • Ling WANG, E SUN, Jian HOU, Jin-di XU, Shu-chen GUO, Ying-jie WEI, Xiao-bin JIA
    Acta Pharmaceutica Sinica. 2021, 56(10): 2849-2857.

    The metabonomics method was used to explore the processing and synergistic mechanism of epimedium fried with suet oil in warming the kidney and enhancing yang. The kidney-yang deficiency rat model was established by injection of hydrocortisone. Then the UPLC-Q-TOF-MS (ultra-performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry) metabolomics method was combined with multivariate statistical analysis methods and univariate statistical analysis to screen and identify kidney-yang deficiency potential biomarkers in plasma and urine samples. Finally the metabolic regulation mechanism of suet oil group, the epimedium raw product group, the epimedium heating product group, and the epimedium fried with suet oil group improved kidney-yang deficiency was analyzed. The results showed that the plasma and urine metabolism of rats with kidney-yang deficiency induced by hydrocortisone showed obvious trajectory changes. 15 biomarkers related to kidney-yang deficiency were identified in plasma and urine, involving 5 metabolic pathways, namely glycerophospholipid metabolism, sphingolipid metabolism, sulfur metabolism, glyoxylate acid and dicarboxylate metabolism, and cysteine and methionine metabolism. The metabolic pathway of epimedium fried with suet oil warming kidney and promoting yang involved glycerophospholipid metabolism, cysteine and methionine metabolism, and the two processing factors of epimedium fried with suet oil "heating" and "suet oil" enhanced its function of warming the kidney and promoting yang by regulating glycerophospholipid metabolism, cysteine and methionine metabolism, respectively. In this way, the processing and synergistic mechanism of epimedium fried with suet oil was clarified. The animal experiments involved in this article comply with ethical standards and have been approved by the Animal Ethics Committee of Jiangsu Provincial Academy of Chinese Medicine (approval number: AEWC-20200702-119).

  • Yue YANG, De-feng LI, Ting LUO, Hao-liang SHI, Yong-qiang ZHANG
    Acta Pharmaceutica Sinica. 2021, 56(10): 2742-2760.

    The structural modification of natural product represents a powerful tool for anti-cancer drug discovery. Noscapine, as a phthalideisoquinoline alkaloid from opium, has been used as an over-the-counter antitussive drug with excellent oral bioavailability and low toxicity. Recently, the potential of this compound as a particularly attractive lead for anti-cancer drug discovery has been demonstrated. Multiple mechanisms, especially the interference of tubulin polymerization, might be involved. Thereafter, various structural modifications based on semisynthetic routes, which aims to improve the anti-cancer activity and pharmacokinetic properties, as well as to probe the mechanism, has been performed. Several analogues are emerging as possible candidates as novel anticancer therapies. This perspective mainly discusses the advancing noscapine and related analogues in the fight against malignant disease in recent years. Furthermore, the future directions of this evolving field were also preliminary prospected.

  • An-na ZENG, Xue-han WANG, Ai-ping LÜ, Zhi-jun YANG
    Acta Pharmaceutica Sinica. 2021, 56(10): 2612-2621.

    Pulmonary drug delivery agents deliver drugs directly to the lung tissue to obtain higher local concentration, which is beneficial to the treatment of lung diseases, and may reduce the systemic side effects. Therefore, it has become the preferred drug for the treatment of many lung diseases. However, the drugs entering the lungs are easily cleared by the lung tissues, which reduce the retention time of the drugs in the lungs and affects the efficacy. Although particles with a smaller particle size (1-5 µm) are easily inhaled into the lungs, they are also easily swallowed and cleared by lung macrophages. While the porous polymer microspheres (PPMS) with larger geometric diameter (Dg > 5 µm) and low density (ρ < 0.4 g·cm-3) can not only effectively avoid the phagocytosis of alveolar macrophages, but also have a high effective deposition rate in the lungs due to the appropriate aerodynamic diameter, moreover, the polymer is biodegradable and non-toxic, so it has become a research hotspot for pulmonary drug delivery carriers. This article combined with the lung clearance mechanism of granules, summarized the preparation materials and methods of PPMS, as well as its quality control, etc. Furthermore, opinions are also put forward for the development of PPMS, to provide a reference for the in-depth study of PPMS.