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  • Li HAN, Hong-peng LI, Wen-ling LI
    Acta Pharmaceutica Sinica. 2020, 55(11): 2558-2569.

    Resveratrol possesses a wide range of biological activities, such as anti-cancer, anti-oxidation, induction of apoptosis, etc., but its poor drug properties, rapid metabolism, low target selectivity and bioavailability limit its application value. Studies have shown that modification of the structure of natural compounds can improve their pharmacological activities. To improve the bioavailability of resveratrol, many researchers have undertaken the synthesis and activity evaluation of resveratrol derivatives and analogues. They have modified the phenolic hydroxyl groups, double bonds and benzene ring of resveratrol so as to further understand the interactions among functional groups and its structure-activity relationship. In this paper, we review the chemical structures, synthetic methods and mechanisms of biological activity of resveratrol monomer derivatives as well as their related therapeutic applications, especially in the anticancer area over the last decade. This will provide some reference value for the further research and development of resveratrol-related drugs.

  • Xiang YUAN, Bing HAN, Zi-ming FENG, Jian-shuang JIANG, Ya-nan YANG, Pei-cheng ZHANG
    Acta Pharmaceutica Sinica. 2020, 55(11): 2674-2678.

    Three butylphthalide derivatives were isolated from the Rhizome of Ligusticum chuanxiong using a series of isolation and purification approaches including macroporous resin, ODS-A column, Sephadex LH-20 and preparative HPLC. These structures were elucidated based on extensive spectroscopic data (UV, IR, HR-ESI-MS and NMR) and identified as (3Z, 3aE)-(6R, 7R, 2'S)-6-hydroxy-7-(2-carboxyl-2-hydroxyethylthio)-3-(2-hydroxybutylidene)-4, 5, 6, 7-tetrahydro-phthalide (1), (3Z, 3aZ)-3-butylidene-6, 7-dihydroxy-4, 5, 6, 7-tetrahydro-phthalide 7-O-α-D-glucopyranosyl-(1→2)-β-D-fructo-furanoside (2) and 3-(3-β-D-glucopyranosyloxy-butylidene)-7-hydroxy-phthalide (3).

  • Qing-hua WANG, Ting-ting DU, Zhi-hui ZHANG, Ming JI, Hai-yu HU, Xiao-guang CHEN
    Acta Pharmaceutica Sinica. 2020, 55(10): 2273-2280.

    In recent years, with rapid advances in chlorogenic acid (CGA) research, it has become widely used in medicine, the chemical industry and health care products, with the potential for broad application. CGA is a water-soluble phenolic natural product and is extensively distributed in a variety of plants. Numerous studies have shown that CGA has strong biological activities including antibacterial, antiviral, antitumor, antioxidative, anti-inflammatory and metabolic regulatory activities. This review summarizes the pharmacological effects as well as the underlying mechanisms of CGA, providing an important theoretical basis for further research on CGA drug targets and potential mechanisms.

  • Jie-hong LIN, Hong-rui YIN, Hong SHAO, Gang CHEN, Mei LIN
    Acta Pharmaceutica Sinica. 2020, 55(10): 2435-2441.

    We utilized a multi-step derivatization gas chromatography-mass spectrometry method for the determination of common amino acid enantiomers, combined with deuterated hydrochloric acid hydrolysis, to identify nine trace D-amino acids in thymalfasin. We optimized the conditions for multi-step derivatization, the volume of reagent for redissolving samples, and the conditions for chromatography and mass spectrometry with isopropanol and trifluoroacetic anhydride as derivatization reagents, and validated the procedure, including sensitivity, linear range, precision, accuracy and recovery. Sixteen pairs of D/L-amino acids and glycine derivatives were separated within 29 min, with the limit of quantification as low as 0.09-2.79 μmol·L-1. Nine amino acid derivatives of thymalfasin showed a good linear relationship within the concentration range examined (r2>0.992 3). The precision results showed that RSD values were less than 10.90%. Accuracy test results of a reference substance ranged from 76.69% to 128.18%. Average recoveries of spiked samples ranged from 70.41% to 125.39%. For the nine D-amino acids assayed, D-Asp and D-Glu content in six batches of thymalfasin were highest, ranging 0.41%-0.49% and 0.25%-0.33%, respectively, with others less than 0.25%. The method is sensitive, efficient and reliable, available for seventeen common amino acids and their enantiomers, and works well with simultaneous determination of nine trace D-amino acids in thymalfasin, providing a reference for the comprehensive control of racemic peptide impurities in this synthetic polypeptide drug.

  • You-yuan LU, Sheng GUO, Hui YAN, Fang ZHANG, Han-qing WANG, Ling JIN, Jin-ao DUAN
    Acta Pharmaceutica Sinica. 2020, 55(10): 2466-2477.

    The fruit of Lycium barbarum L. (FLB) is a food and medicinal herb. Identifying suitable production regions for this plant would be beneficial to its cultivation and production. In this study, the Maxent model was used to identify ecologically suitable regions for the growth of L. barbarum L. In addition, based on its chemical composition, the suitable regions for production were identified by literature analysis and chemometrics. The results show that suitable regions for L. barbarum L. culture are mainly distributed in the northwest of China; suitable regions for the production of medicinal FLB were mainly concentrated in the district of Ningxia, Baiyin, Jiuquan and Zhangye of Gansu, and parts district in west of Inner Mongolia. All are the traditional production regions for FLB, which is consistent with the good quality of FLB produced in Ganzhou in ancient times, and the genuine medicinal materials of FLB produced in Zhongning of Ningxia today. The suitable regions for edible FLB were mainly distributed in northwest of Qinghai, Jiuquan and Zhangye of Gansu, as well as Aksu and Kizi sukirgiz of Xinjiang. The fruit type index of FLB in these regions is large, and the content of fructose and glucose in the fruit is high, which satisfies the edible commodity property. The study results lay a foundation for realizing the regional distribution and development of L. barbarum based on its different uses.

  • Xiao-juan ZHANG, Yan-zhi WANG, Man-qian LI, Zhi-min SONG, Yan GUO, Xue-yu HU, Wei-sheng FENG
    Acta Pharmaceutica Sinica. 2020, 55(10): 2421-2427.

    We separated and purified five chemical constituents of dried ginger by Diaion HP-20, Sephadex LH-20, silica gel and semi-preparative high performance liquid chromatography. Five gingerols were identified by physicochemical properties and MS and NMR spectroscopy techniques:4-(2-butyl-6-methyl-4H-pyran-4-yl)-2-methoxyphenol (1), 4-(2-hexyl-6-methyl-4H-pyran-4-yl)-2-methoxyphenol (2), 1-(4-hydroxy-3-methoxyphenyl)tridecane-3, 5-diol (3), [10]-gingerdiol (4) and 1-[1-(4-hydroxy-3-methoxy phenyl)-3-oxodecan-5-yl]pyrrolidin-2-one (5a, 5b). Compounds 1-3, 5a, 5b are new compounds.

  • Ya-hui DUAN, Xue-mei QIN, Zhen-yu LI
    Acta Pharmaceutica Sinica. 2020, 55(10): 2414-2420.

    Asthma is a chronic inflammatory disease involving eosinophils, mast cells, lymphocytes, neutrophils and other inflammatory cells and immune components. Chinese medicine has unique advantages in the treatment of asthma. In this study an ovalbumin (OVA)-induced asthma model in rats was used to verify the effect of the total sesquiterpenoids of Flos Farfarae (F.F.S) on asthma. The results show that the F.F.S has anti-asthmatic effects. Metabolomic analysis showed that 25 metabolites were changed in asthmatic rats, and 18 of them could be attributed to F.F.S. F.F.S. can block the over-activation of p65 NF-κB, preventing the transmission of pro-inflammatory factor signals to cells. F.F.S. thus could reduce the over-activation of inflammatory cells, inhibiting the secretion of inflammatory factors and further alleviating asthma inflammation. This study lays a foundation for further new drug research. The mechanism of F.F.S. on asthma needs further investigation.

  • Le-ting SI, Hong-fei NI, Qian LI, Lian-jun LUAN, Yong CHEN, Xue-song LIU, Yong-jiang WU
    Acta Pharmaceutica Sinica. 2020, 55(10): 2449-2453.

    A high performance liquid chromatography charged aerosol detector (HPLC-CAD) method was established for the simultaneous determination of five saponins (notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1, Ginsenoside Rd) in Yaobitong capsule, providing a method for quality control. The sample was extracted with methanol and chromatographic separation was performed on a Waters Xbridge Phenol column (150 mm×4.6 mm, 3.5 μm) using acetonitrile-water as the mobile phase with gradient elution at a flow rate of 1.0 mL·min-1. The column temperature was 30℃ and the injection volume was 10 μL. The nebulizer temperature of CAD was 35℃ and the air pressure was 60.2 psi, the filtration was 3.6 s, and the collection frequency was 5 Hz. Notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1 and ginsenoside Rd showed a good linear relationship in the range of 16.96-203.5 μg·mL-1 (R2=0.999 3), 54.46-653.5 μg·mL-1 (R2=0.999 3), 10.96-131.5 μg·mL-1 (R2=0.999 6), 51.50-618.0 μg·mL-1 (R2=0.999 0), 15.94-191.3 μg·mL-1 (R2=0.999 4), respectively. The average recoveries were 98.96%, 100.8%, 94.76%, 100.1%, 103.1%, and RSDs were 0.87%, 1.46%, 1.85%, 2.06%, 0.96% (n=6), respectively. The proposed method is accurate, simple and reliable, and can be used for the determination of five saponins in Yaobitong capsule.

  • Ming-hui LI, Shu-ling WANG, Cheng CAO, Feng-lian CHEN
    Acta Pharmaceutica Sinica. 2020, 55(10): 2375-2380.

    To screen active components of Desmodium styracifolium in protecting calcium oxalate monohydrate (COM) -induced human proximaltubular epithelial cell (HK-2) damage model, and furtherly explore its mechanism of action, total flavonoids of Desmodium styracifolium (TFDS) and eight flavonoids (schaftoside, isoschaftoside, vicenin-2, isovitexin, isoorientin, apigenin, luteolin and genistein) were tested by COM-induced HK-2 damage model. MTT assay was used to detect the effects of different components on the cell viability of COM-induced HK-2 damage model. The lactate dehydrogenase (LDH) release in the cell supernatant and the activity level of superoxide dismutase (SOD) and reactive oxygen species (ROS) of cell were detected by the kit. Western blot was used to detect the expression levels of NLRP3, caspase-1, HMGB1 in HK-2 of different groups. Compared with the model group, the cell activity was significantly increased after 24 h co-culture with TFDS and four flavonoids (isoorientin, apigenin, genistein and luteolin). These active components can reduce the LDH leakage and ROS in cell supernatant and increase the activity of SOD, with regulating the expression of NLRP3, caspase-1, HMGB1. TFDS, apigenin, isoorientin, luteolin and genistein can protect COM-induced HK-2 cell damage, including enhancing cell viability, protecting cell membrane integrity and enhancing oxidative stress, and regulate the expression of proteins related to NLRP3 inflammasome.

  • Le SUN, Xiao-mei CHEN, Chong-ming WU, Shun-xing GUO
    Acta Pharmaceutica Sinica. 2020, 55(10): 2322-2329.

    Dendrobium officinale Kimura et Migo (D. officinale) has been used as a valuable traditional Chinese medicine for more than 2 000 years in China. Modern research has confirmed a wide range of pharmacological activities, such as regulating blood sugar, improving gastrointestinal inflammation, and regulating immunity. Polysaccharides are the main active ingredients of D.officinale. With the intensive studies of the pharmacological activities of D.officinale, evidence for the pharmacological effects and potential mechanisms of D.officinale polysaccharides has increased dramatically. In this review, we summarized the latest progress in the pharmacological and mechanical studies of D.officinale polysaccharides, and based on the pharmacological efficacy and oral absorption and utilization characteristics of D.officinale polysaccharides, it is proposed that regulating the gut microbiota may be one of the key mechanisms for D.officinale to exert its beneficial effects. Research on the mechanism of D.officinale polysaccharides puts forward new research directions and prospects.