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  • 2021 Volume 56 Issue 1
    Published: 08 January 2021
      

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  • WANG Jia-ning, WANG Xiao-yu, SHI Ting-ting, CHEN Lin-xin, MEI Hu
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    Since the beginning of this century, idiosyncratic adverse drug reactions (IADRs) have been proven to be closely associated with human leukocyte antigen (HLA). In this paper, the mechanisms of the HLA-restricted IADRs, including the “p-i” concept, the “altered peptide repertoire” model, and the “altered TCR repertoire” model, were reviewed in detail. The recent advances summarized in this paper can provide valuable references for the development of personalized and precision medicine as well as drug safety evaluation.
  • WANG Yue, FAN Hui-hong
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    To analyze the quality control technologies and research of polysaccharides in recent years. By searching the domestic and international literatures and practical experiences in recent years, a comprehensive integrated progress was collated and induced. Polysaccharide drugs have complex structures and their quality control is difficult. The quality control of polysaccharides should be carried out from three aspects: qualitive test, quantitative test, and safety test. Various technologies and methods such as infrared spectroscopy technology, multi-angle laser light scattering, ion chromatography, liquid chromatography, and nuclear magnetic resonance techniques should be used comprehensively to control the physical properties, molecular weight distribution, sugar composition and sugar structure, content, impurity control, and safety of polysaccharide drugs.
  • XIA Zhao, ZHANG Hai-xin, XU Tian-qi, CHEN Yi-min, ZHOU Guang-xiong
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    OBJECTIVE To investigate phenylpropanoids from the dried fruits of Xanthium sibiricum Patrin ex Widder (Xanthii Fructus). METHODS The compounds were isolated and purified by silica gel column chromatography, ODS chromatography, Sephadex LH-20 and semi-preparative HPLC. Base on HR-ESI-MS and NMR, their structures were identified. The anti-inflammatory activity of the isolated compounds was evaluated by lipopolysaccharide(LPS)-induced macrophage RAW 264.7 as a screening model. RESULTS A total of 24 compounds were isolated from the ethyl acetate fraction of 95% ethanol extract and identified as c-veratroylglycol(1), β-hydroxypropiovanillone(2), ferulaldehyde(3), dihydrodehydrodiconifery alcohol(4), balanophonin(5), lariciresinol(6), guaiacylglycerol(7), 3-hydroxy-l-(4-hydroxy-3, 5-dimethoxyphenyl)-1-propanone(8), salicifoliol(9), 6-(4-hydroxy-3-methoxyphenyl)-3, 7-dioxabicyclo[3.3.0] octan-2-ol(10), ficusal(11), jatrointelignan D(12), icariol A2(13), isolariciresinol(14), ehletianol C(15), (7R, 7'R, 7”S, 7‴S, 8S, 8'S, 8”S, 8‴S)-4”, 4‴-dihydroxy-3, 3', 3”, 3‴, 5, 5'-hexamethoxy-7, 9';7', 9-diepoxy-4, 8”; 4', 8‴-bisoxy-8, 8'-dineolignan-7”, 7‴, 9”, 9‴-tetraol(16), (7R, 7'R, 7”R, 7‴S, 8S, 8'S, 8”S, 8‴S)-4”, 4‴-dihydroxy-3, 3', 3”, 3‴, 5, 5'-hexamethoxy-7, 9'; 7', 9-diepoxy-4, 8”;4', 8‴-bisoxy-8, 8'-dineolignan-7”, 7‴, 9”, 9‴-tetraol(17), 2-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)-propan-1, 3-diol(18), 2, 3-bis-(4-hydroxy-3-methoxyphenyl)-3-methoxypropanol(19), evofolin B(20), threo-guaiacylglycerol-8-vanillin ether(21), erythro-guaiacylglycerol-8-vanillin ether(22), cleomiscosin B(23), 27-p-E-coumaroyloxyursolic acid(24). CONCLUSION Compounds 6-24 are obtained from this plant for the first time. Compounds 14, 21, and 23 show anti-inflammatory activity in LPS-induced RAW 264.7 macrophages with the IC50 values of (28.14±1.89), (16.78±0.68), and (38.42±2.15) μmol·L-1, respectively.
  • ZHANG Xin-yuan, SUN Xiang-ming, SONG Hui, XU Qian, WANG Mei-yao
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    OBJECTIVE To select the best extraction method for total flavonoids in Cuscuta chinensis and determine the estrogenic activity of the extract. METHODS A method for the content determination of total flavonoids in Cuscuta chinensis was established by UV spectrophotometry. The orthogonal design L4(23) was used to optimize and screen the ultrasonic extraction, reflux extraction and flash extraction with the content of total flavonoids as the evaluation index. The uterine coefficient and endometrial thickness were used to evaluate the estrogenic activity of Cuscuta chinensis in immature mice. RESULTS The flash extraction method showed the shortest time and highest total flavonoids content among the three extraction methods. The extraction process was as follows: 70% ethanol as the extraction solvent, the ratio of material to liquid of 1∶40, the cumulative extraction time of 2 minutes and the extraction voltage of 100 V. The results of estrogen activity study showed that the total flavonoids in Cuscuta chinensis could significantly increase uterine weight and endometrial thickness in immature mice. CONCLUSION The flash extraction method is energy efficient and suitable for the extraction of total flavonoids in Cuscuta chinensis. The total flavonoids in Cuscuta chinensis has good estrogenic activity, which can provide a reference for the rational development and utilization of Cuscuta chinensis functional products.
  • YANG Huan,bI Shu-ning, WEI Qiu-ren, WEI Zhen, CHEN Liang, XIE Song-qiang
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    OBJECTIVE To explore the inhibitory effects of fucoxanthin on the migration and invasion of ESCC cells (EC109 and EC9706), and elucidate the underlying molecular mechanisms. METHODS MTT assay was used to detect the cell viability of ESCC cells. Wound healing, Transwell migration and invasion assays were performed to assess the effect of fucoxanthin on migration and invasion in ESCC cells. Western blotting was employed to detect the protein levels of PI3K, p-PI3K (Tyr607), AKT, p-AKT (Ser473), MMP-2, MMP-9, N-Cadherin and E-Cadherin. RESULTS Fucoxanthin inhibited the viability of EC109 and EC9706 cells,with IC50 values of (51.49±4.15) and (52.44±3.38) μmol·L-1, respectively. Interestingly, fucoxanthin also dose-dependently suppressed the migration and invasion of EC109 and EC9706 cells, and downregulated the protein levels of MMP-2, MMP-9 and N-Cadherin and enhanced the expression of E-Cadherin. Further investigations showed that the protein levels of p-PI3K (Tyr607) and p-AKT (Ser473), but not the total protein of PI3K and AKT, were substantially suppressed upon fucoxanthin treatment. CONCLUSION Fucoxanthin can drastically diminish the migration and invasion of ESCC cells, and the underlying molecular mechanism might be blocking PI3K/AKT signaling pathway.
  • LIU Shen-huan, YANG Fu-wei, CAI Yao, QIU Li-peng, CHEN Jing-hua
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    OBJECTIVE To synthesize a stimulus-sensitive precursor polymer (PEG-DOX) from polyethylene glycol and doxorubicin, encapsulate melphalan(MEL) to prepare MEL/PEG-DOX nanometer micelles, and investigate its synergistic anti-tumor effect in vitro. METHODS Through Schiff base reaction, the pegylated dithionyl hydrazide (TPH) was combined with DOX to form a pH/reduction sensitive PEG-DOX prodrug nanocarrier, and MEL/PEG-DOX loaded micelle was prepared by its self-assembly property.The morphology was observed by transmission electron microscopy, the particle size and potential were measured by particle size analyzer, drug loading and encapsulation rate were measured by ultrafiltration, drug release of micelles was evaluated by dialysis, and cytotoxicity was evaluated by MTT. RESULTS The stimulation response PEG-DOX precursor polymer was verified by H-NMR.The mean particle size of peg-dox carrier was (188±2.4) nm, and the polydispersion coefficient (PDI) was (0.255±0.008). The mean particle size of MEL/PEG-DOX loaded micelles was (299.7±2.4) nm, the polydispersion coefficient (PDI) was 0.301±0.03, and the Zeta potential was (-0.385±0.02) mV. DOX drug-polymer interactions (14.85±0.24)%, the encapsulation rate was (85.78±0.37)%, MEL drug-polymer interactions (7.36±0.36)%, the encapsulation rate was (38.79±0.42)%.The results of drug release experiments in vitro showed that MEL/PEG-DOX micelles were sensitive to reduction and pH, and the reduction sensitivity was greater than that of pH. Cytotoxicity analysis showed that DOX and MEL were released together in cells, achieving the joint killing of tumor cells. CONCLUSION MEL/PEG-DOX can be specifically released in the tumor microenvironment, which has a coordinating effect on tumor cells and a good application prospect.
  • WANG Wen-ping, CHEN Yuan, HAI Ya-feng, LI Bo-li, LIU Chen
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    OBJECTIVE To obtain nano-sized extract powder of total flavonoids from Flos Sophorae by combinational application of DES/ethanol extraction and anti-solvent precipitation. METHODS Flos Sophorae was extracted by ethanol or DES (choline chloride and triethylene glycol at molar ratio of 1∶2 containing 20% water). The extraction liquids were mixed with water to obtain suspensions, followed by freeze-drying to prepare extract powders. The extracts were compared on their appearance, particle size, saturated solubility and in vitro dissolution profiles in water. RESULTS Content of total flavonoids in extraction liquid was (17.72±1.54) mg·g-1 for DES and (4.02±0.35) mg·g-1 for ethanol, and that was 129.29 and 20.29 mg·g-1 for DES and ethanol extract powders, respectively. The extract powder of both DES and ethanol showed a larger solubility in water than rutin itself. And their dissolution rates reached over 85% at 20 min, whereas rutin released less than 60% at 2 h. CONCLUSION This method is simple and efficient, the obtained extract possesses favorable solubility and dissolution properties. DES shows a better performance than ethanol during the process.
  • ZHU Ying, HAN Xue-mei, KE Xiao, LI Xi-xuan, QIN Yan-jie, RANG Ying, ZHAI Xue-jia, LU Yong-ning
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    OBJECTIVE To establish a HPLC-MS/MS method for quantitative determination of the main active ingredients of Acanthopanax senticosus extracts and Hypericum perforatum L. extracts in rat plasma, and study combination pharmacokinetics of main active ingredients in rats. METHODS The chromatographic separation was performed on Welch Ultimate XB-C18(2.1 mm×100 mm, 4.6 μm) column as the mobile phase was acetonitrile (containing 0.1% formic acid)-0.1% formic acid in water (containing 5 mmol·L-1 ammonium acetate). The flow rate of 300 μL·min-1 was used for gradient elution, and the electrospray ion source was used for simultaneous scanning of positive and negative ions, and the multi-reaction monitoring mode was used for detection. RESULTS The results show that the established method had good precision and accuracy, and the extraction recovery rate was basically in line with the requirements of biological sample analysis methods. CONCLUSION Pharmacokinetic results show that compared with single administration, eleutheroside E tmax is shortened, hypericin ρmax is increased, and t1/2 is prolonged. The pharmacokinetic results indicat that when the extract of Acanthopanax senticosus is combined with the extract of Hypericum perforatum L., it might produce synergistic anti-depression effect in vivo by increasing the blood concentration of hypericin and shortening the peak time of eleutheroside E.
  • ZHANG Han-zhi, SUN Ning, QIN Feng, LUO Wen-yan, ZHAO Jing-dan, WEN Hong-liang, QIU Ya, LIU Hao, LI Min
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    OBJECTIVE To establish a high performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (HPLC-Q/TOF-MS) method for the structural analysis of the components in polymyxin E sulfate, and identify the vinyl components in aid of photochemical reaction. METHODS Based on the mass data of polymyxin E1 and E2, the strategy for structure analysis of polypeptide antibiotics was summarized. The structure of polymyxins was determined by accurate molecular weight and characteristic fragment ions. The amino acids contained in the components were judged by amino acid residue ions. The photochemical (Paterno-Büchi reaction) was performed under a low-pressure mercury lamp (emission band at 254 nm), and the epoxidation product of the vinyl polymyxin E1 was verified by MS/MS. RESULTS A new fragmentation route was proposed for the first time in this paper. According to the above-mentioned methods, the structures of 21 components were analyzed. Two components of vinyl polymyxin E1 and E2 were found and it was the first time to identify the structure of vinyl polymyxin E1 by Paterno-Büchi reaction combined with characteristic ions analysis. These two novel components were named as 7'-vinyl polymyxin E1 and 6'-vinyl polymyxin E2, respectively. CONCLUSION 7'-Vinyl polymyxin E1 and its photochemical product, 6'-vinyl polymyxin E2, are reported for the first time. The study provides an effective solution for the identification of the components including vinyl ones in polymyxins.
  • CHE Jing, XIA Hou-lin, DENG Yu-jiao, GUAN Yong-mei, YANG Ming, MA Hong-yan
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    OBJECTIVE To establish a method for determination of heavy metals and harmful elements in Periplaneta americana, and conduct analysis according to international and domestic heavy metal limit standards. METHODS The contents of five heavy metal elements including Cd, As, Pb, Hg and Cu in 13 batches of samples were determined by ICP-MS. RESULTS Five elements showed good linearity within the test ranges (r≥0.999 2), with recovery rate ranging from 88.5% to 117.0% (RSD was 0.45%-3.96%). According to international and domestic standards, the unqualified rates of 13 batches of samples were between 7.69% and 100%, and the unqualified rate varied greatly. CONCLUSION The method established in this study can accurately determine the contents of heavy metals and harmful elements in Periplaneta americana. Among them, it is common for Cu to exceed the standard due to large difference in the set limits, and most standards do not require it. There are regulations on the limit of Pb, but the set value is relatively wide, and the limit can be appropriately lowered. The limits of Cd, As and Hg in the international standards have little difference compared with the domestic standards, and the unqualified rates are similar. It is considered that the limits of the three elements are feasible. It is necessary to establish a targeted standard for the limit of heavy metals and harmful elements in Periplaneta americana.
  • BAI Yun-xia, SONG Xiao-ling, QU Bi, LIANG Yue, ZHANG Hui-wen
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    OBJECTIVE To establish a new comprehensive method to evaluate the quality of Granati Pericarpium collected from 11 different regions by HPLC fingerprint combined with grey correlation analysis, cluster analysis and discriminant analysis. METHODS HPLC fingerprint was established with mobile phase consisting of methanol and 0.1% phosphoric acid, and the contents of gallic acid, punicalagin and ellagic acid were determined, while the results of the HPLC fingerprint and chemical composition of Granati Pericarpium were processed by grey correlation, cluster and discriminant analysis. RESULTS The HPLC fingerprint of the samples had good similarity. Twenty-one common peaks were confirmed. The grey correlation analysis showed that S5 (Jiangsu), S1 (Sichuan), S3 (Hebei) and S8 (Anhui) had better medical value. The cluster analysis indicated that the Granati Pericarpium collected from 11 different regions could be divided into five categories, among which S5 (Jiangsu) belonged to the first class S1 (Sichuan),S2 (Jiangsu) and S3 (Hebei) belonged to the third class, S7 (Shanxi) and S8 (Anhui) belonged to the second class. The results of three kinds of analysis were mutually validated and complementary. CONCLUSION HPLC fingerprint combined with gray correlation, cluster and discriminant analysis can comprehensively evaluate the quality of Granati Pericarpium. This paper establishes a scientific, accurate and reliable method, which can be used for comprehensive evaluation of the internal quality of Granati Pericarpium.
  • WANG Zhi-hong, LI Ting, ZHAO Zi-nan, ZHANG Tian, LI Chao, XUE Wei, LI Ke-xin, TAN Ling
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    OBJECTIVE To evaluate rapidly the effectiveness, safety and economics of nimotuzumab(NTZ)in the treatment of nasopharyngeal carcinoma using the HTA method recommended by WHO and provide evidence-based support for clinical drug use. METHODS Retrieved from PubMed, Embase, Cochrane Library, CNKI, Wanfang database and CBM, etc., health technology assessment(HTA)related website and database were searched systematically to select HTA report, Meta-analysis/systemic evaluation and pharmacoeconomic study about NTZ. According to the inclusion and exclusion criteria, two researchers independently screened the literatures, extracted and summarized the data, then performed qualitative description of results. RESULTS Totally 5 Meta-analysis were retrieved. No pharmacoeconomic studies and related HTA reports were retrieved. RESULTS of the study showed that compared with the control group, NTZ can be used to treat advanced nasopharyngeal carcinoma, effectively control the development of the disease, prolong the survival time of patients, improve the prognosis, with good effect and no serious adverse reactions. CONCLUSION NTZ has favorable efficacy and safety in the treatment of advanced nasopharyngeal carcinoma.In the future, pharmacoeconomic research on NTZ can be considered to supplement the evidence of economic evaluation.