Home Latest Articles
Latest Articles
  • Shi-wei ZHU, Xiao-xia GAO, Jun-sheng TIAN, Xue-mei QIN, Guan-hua DU, Yu-zhi ZHOU
    Acta Pharmaceutica Sinica. 2019, 54(2): 235-244.

    Depression, a global disease with various pathogenic factors, is seriously affecting human physical and mental health. In Chinese traditional medical theory, the disease belongs to the category of "Yu Zheng". At present, on the one hand, adverse reactions to antidepressant western medicine are becoming more and more prominent. On the other hand, the study of their antidepressant active ingredients and compatibility mechanisms has become a difficult field in the traditional Chinese medicine compounds due to their complexity. The Chinese antidepressant herb-pairs has become a hot topic in the field of antidepressant research. Herb-pair is the core of traditional Chinese medicine compound. In addition, the compound itself is a herb-pair. The study of traditional Chinese antidepressant herb-pairs is more conducive to clarify the compatibility mechanism of herb interaction and the mechanism of antidepressants on the body.Therefore, this paper systematically expounds antidepressant herb-pairs from the study of material, pharmacokinetics and efficacy, which aims at providing theoretical support for the compatibility mechanism of antidepressant herb-pairs and the research of new antidepressant drugs.

  • Jing CHEN, Zhen XU, Xue ZHANG, Yan-peng LI, Chun-sheng LIU
    Acta Pharmaceutica Sinica. 2019, 54(2): 373-379.

    In order to determine the differences in structure and optimum isolation conditions of Glycyrrhiza uralensis endophytes from different habitats, plate-separation method was used to identify endophytes in G. uralensis from Gansu, Ningxia, Inner Mongolia, Xinjiang, and Beijing. The isolation parameters were defined by investigating various concentrations and sterilization time of NaClO solution. The strains were identified by morphological and molecular biological methods. The results showed that 5% NaClO solution and sterilization time of 5 min were the optimal surface sterilization conditions. Among 129 strains of G. uralensis from 5 producing areas, 438 strains of endophytic fungi were isolated and belonged to 5 orders, 7 genera, and 11 species. Among them, 4 taxa were firstly isolated from the licorice in China. Fusarium was a common genus among the 5 regions. There were differences in the composition and structure of the endophytic fungi of G. uralensis from different habitats. Diversity analysis showed that the endophytic fungi diversity in Gansu was the highest and that of Beijing was the lowest. The comprehensive analyses indicated that the endophytic fungi of G. uralensis are diverse, and there were differences among the number, composition and population of endophytic fungi in five producing areas of Gansu, Ningxia, Inner Mongolia, Xinjiang and Beijing.

  • Yi-xiu ZHAO, Xue LIU, Yan ZHANG
    Acta Pharmaceutica Sinica. 2019, 54(2): 228-234.

    Atherosclerosis refers to vascular pathological changes in which vascular lumen was narrowed or blocked by cholesterol or fat existed in vascular endothelium, which could induce serious cardiovascular events. The pathogenesis of atherosclerosis is complicated extremely. Vascular endothelial dysfunction initiated the plague formation and deterioration, which determined the prognosis of atherosclerosis. Circular RNA (circRNA) is a special endogenous non-coding RNA, which has become a research hotpot in the field of non-coding RNA. This review aims to bring together the recent research on the pathogenesis and pathological process of endothelial dysfunction, and the regulative effect of circRNA on it. Our article will provide new targets and new ideas for the research and development of anti-atherosclerosis drugs.

  • Xue-fei CHEN, Xiang-yu HOU, Xiao-yan CHEN, Da-fang ZHONG
    Acta Pharmaceutica Sinica. 2019, 54(2): 360-365.

    Nifedipine, a calcium channel antagonist, is metabolized mainly by CYP3A4 to dehydronifedipine. A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously determine nifedipine and dehydronifedipine in human plasma using d6-nifedipine/d6-dehydronifedipine as internal standards. After extraction from the plasma by protein precipitation, the analytes and internal standard were separated on a Hypersil Gold C18 (50 mm×2.1 mm, 1.9 μm). The mobile phase consisted of methanol and 5 mmol·L-1ammonium acetate aqueous solution (0.1% formic acid). Positive electrospray ionization was performed using multiple reaction monitoring (MRM) with transitions of m/z 347.3→254.1 for nifedipine, m/z 345.2→283.9 for dehydronifedipine, m/z 353.3→257.1 for d6-nifedipine, m/z 351.2→286.9 for d6-dehydronifedipine. The method had a linear calibration curves over the concentrations of 0.10-80.0 ng·mL-1 for nifedipine and 0.050-40.0 ng·mL-1 for dehydronifedipine. The validated LC-MS/MS method has been successfully used study pharmacokinetic interactions of apatinib (CYP3A4 inhibitor) and nifedipine (CYP3A4 substrate) in human. This clinical trial was approved by the society of ethics and conducted in the first hospital of China medical university.

  • Ming LI, Jian-hui WEN, Fu-yong NI, Xue XIE, Yun WU, Zhen-zhong WANG, Wei XIAO
    Acta Pharmaceutica Sinica. 2019, 54(2): 343-347.

    Chemical constituents from the ethanol extract of Radix Angelicae Pubescentis was isolated and purified through Diaion HP-20 macroporous, silica gel column chromatography, gel filtration over Sephadex LH-20 and preparative HPLC. Two new sesquiterpenoid derivatives were identified as angesesquid A (1) and angesesquid B (2), and their structures were determined. In vitro degeneration model of primary rat disc chondrocytes was used to evaluate the anti-inflammatory activity of these two compounds. The results showed that compounds 1 and 2 had no anti-proliferation effect. Both compounds inhibited the release of NO, but had no inhibitory activity for the release of PGE2. This finding implies that both of these two new sesquiterpenoids could moderately inhibit the inflammatory reaction to some extent.

  • Rong-chang CHEN, Xiao-yu MA, Li-jiao XU, Gui-bo SUN, Xiao-bo SUN
    Acta Pharmaceutica Sinica. 2019, 54(2): 294-300.

    To investigate the effect of scutellarin (Scu) on diabetic cardiomyopathy in mice, type 2 diabetes mellitus was induced by intraperitoneal injection of 50 mg·kg-1 streptozotocin (STZ) into a high-fat diet. Scu was injected intraperitoneally. After 8 weeks, fasting blood glucose and serum biochemical parameters were measured. Masson staining was performed on myocardial tissue. The expression levels of Nrf2, NFκB, AKT and p-AKT in myocardium of mice were observed by Western blot. All the procedures were approved by the Laboratory Animal Ethics Committee of the Peking Union Medical College. The results showed that Scu significantly decreased the heart-body ratio, increased myocardial contractile function, decreased the level of myocardial fibrosis and the expression of collagen I and collagen Ⅲ in myocardium of diabetic mice. Scu can effectively reduce the levels of lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB), malondialdehyde (MDA) in serum of diabetic mice, increase the level of antioxidant enzymes in serum, and inhibit the release of inflammatory factors. Further studies showed that Scu significantly increased Nrf2 nuclear translocation, inhibited NFκB nuclear translocation and increased AKT phosphorylation. It indicates that Scu has significant effect on diabetic cardiomyopathy in mice.

  • Gang BAI, Yuan-yuan HOU, Guo-yu DING, Min JIANG, Jie GAO, Tie-jun ZHANG, Chang-xiao LIU
    Acta Pharmaceutica Sinica. 2019, 54(2): 197-203.

    The quality of traditional Chinese medicine (TCM) is the lifeline for TCM industry. The development of artificial intelligence (AI) has provided new means for the quality management of Chinese medicinal materials (CMM). In this paper, we take the quality marker (Q-marker) as a breakthrough point, focused on the research strategy from chemical markers to Q-markers, picked up the characteristics of the Q-markers from the near infrared spectrum (NIRS), and explored the feasibility of establishing the NIRS assay based on Q-marker. After integrated the biological activity detection and artificial neural network algorithm, we try to establish the relationship between the spectral properties of NIRS and specific efficacy of the CMM. Finally, the bottlenecks will be solved that related to the transmission and traceability of quality attributes in the process of TCM production, quantity change, overall quality management and so on. This system is going to improve TCM quantity scientific and intelligent supervision, and promote the upgrading of traditional TCM industry.

  • Yan-ling SONG, Ling LI, Zhong-yan LIU, Jie LI, Peng-bo ZHANG
    Acta Pharmaceutica Sinica. 2019, 54(2): 335-342.

    Ten novel oleanolic acid (OA) derivatives containing urea or thiourea group were designed and synthesized, the chemical structures were confirmed by 1H NMR, 13C NMR and HR-MS. All of these compounds were evaluated for the inhibitory activity against growth of HepG2 and SGC7901 cells. The results showed that compounds I3 and 3 exhibited significant antitumor activities with IC50 of 9.4 and 5.5 μmol·L-1, respectively. Molecular docking studies showed that all these compounds exhibit inhibitory ability against mTOR kinase. Compounds I3 and 3 were further evaluated for the inhibitory activity against mTOR kinase. The results showed that I3 and 3 exhibited strong inhibitory effect on mTOR kinase with IC50 values of 0.83 and 0.26 μmol·L-1.

  • Chun-lei YU, Tian-jiao XU, Xiao-jie ZHANG, Miao-xian DONG, Ying-cai NIU
    Acta Pharmaceutica Sinica. 2019, 54(2): 329-334.

    We were interested in ascertaining differences in developmental neurotoxicity in normal and blood-stasis pregnant mice administered orally Rhizoma Curcumae and the underlying molecular biology mechanisms of any differences. To answer these questions, a blood stasis model was induced by being immersion in ice water. C57BL/6 mice with blood stasis, normal C57BL/6 mice, Nrf2 knock out (KO) mice with blood stasis were randomized into control groups and Rhizoma Curcumae exposure groups. The pregnant mice were administered Rhizoma Curcumae during pregnant day 5 to day 18. The neurodevelopment reflex was examined by the positive occurring time of avoidance precipice reflex tests. Measurement of glutathione (GSH) in brain of the offspring was performed by colorimetric assays. Transcription factor NF-E2-related factor 2 (Nrf2), glutamate cysteine ligase catalytic subunit (GCLc), and glutamate cysteine ligase modifier subunit (GCLm) mRNA and protein expression in brain of the offspring were examined by real-time RT-PCR and Western blot, respectively. All animal care and experiments procedures were reviewed and approved by the Animal Care and Use Committee of Qiqihar Medical College. Our results demonstrated for the first time evidence that C57BL/6 mice treated with Rhizoma Curcumae (10.0 g·kg-1) extended the positive occurring time of avoidance precipice reflex tests of offspring mice compared with the normal control group (P < 0.05). We could not find any significant change in that of blood-stasis pregnant mice offspring compared with the normal control group (P>0.05). Compared with the normal control group, level of glutathione, mRNA and protein expression of Nrf2, GCLc, and GCLm significantly increased in brain of the offspring of blood-stasis pregnant mice (all P < 0.05). However, mice treated with Rhizoma Curcumae (10.0 g·kg-1) did not change those of offspring (all P>0.05). Knock out Nrf2 using CRISPR/Cas9 extended the positive occurring time of avoidance precipice reflex tests of offspring of blood-stasis pregnant mice (P < 0.05). To conclude, developmental neurotoxicity of the blood-stasis pregnant mice to Rhizoma Curcumae was weaker than that of the normal pregnant mice. Cold-induced Nrf2 activation has important roles in "YOU-GU-WU-YUN" phenomenon of Rhizoma Curcumae.

  • Ming-juan WANG, Shuai KANG, Xuan LIU, Xu WANG, Peng LIU, Zhong DAI, Shuang-cheng MA
    Acta Pharmaceutica Sinica. 2019, 54(2): 354-359.

    Though red yeast rice (RYR) has been used as medicine for centuries, few study has been reported about its biological activities related to traditional medicinal application and marketed RYR showed poor consistency in quality. In this study, with comprehensive investigation of their production processes and field acquisition samples including those from genuine producing area, an ultra performance liquid chromatographic (UPLC) method was firstly established to discriminate RYR for different applications based on their secondary metabolites fingerprint. It was performed on a CAPCELL CORE AQ column (100 mm×4.6 mm, 2.7 μm), with PDA (range:200-650 nm, extracted:237 nm) and ELSD detection. The mobile phase used was water (A) and acetonitrile (B) both containing 0.1% formic acid at gradient elution (0-15 min, 50% B→85% B (linear); 15-16 min, 85% B→50% B (linear) and maintained until 21 min), with a flow rate of 0.5 mL·min-1. The method established was fully validated in agreement with guidelines of Chinese Pharmacopeia. Common metabolites were found in RYR for same application and the fingerprints of RYR for food coloring or brewing from various manufacturers had similarities above 0.90. Meanwhile, significant differences were observed among the fingerprints for various applications and discrimination could be achieved by principal component analysis (PCA). Lovastatin was absence in RYRs for food coloring or brewing, and the fingerprint of traditional medicinal RYR was similar to that of RYR for brewing. However, standardization was required for RYR containing lovastatin because of their significant differences from various manufacturers in fingerprints and lovastatin content. The results demonstrated the feasibility to discriminate RYR for different applications by the secondary metabolites fingerprint method established in this study, which provides a scientific basis to investigate the relationship between biological activities of medicinal RYR and their corresponding secondary metabolites, and further aid their quality standardization and improvement.