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2020 Vol. 38, No. 3

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Mechanism of Jinzhen oral liquid in treatment of coronavirus disease 2019 based on network pharmacology
CAI Mengcheng, YU Chaoqin
2020, 38(3): 193-201. doi: 10.12206/j.issn.1006-0111.202003163
Abstract(10615) HTML (3883) PDF (1354KB)(88)
Abstract:
  Objective  To explore the molecular targets and related potential pathways of Jinzhen oral liquid in the treatment of coronavirus disease 2019 (COVID-19).  Methods  The potential blood-entry active ingredients and targets of Jinzhen oral liquid were retrieved by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). COVID-19 related gene targets were retrieved through GeneCard. Protein-protein interaction network of common targets was constructed by String. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway analysis of the intersection network were conducted by Bioconductor Database.  Results  141 active ingredients were screened according to oral bioavailability and drug similarity. 350 target genes directly related to COVID-19 were obtained from the GeneCard. 47 genes were obtained from the intersection of component-target and disease-target. These genes were mainly involved in response to lipopolysaccharide, oxidative stress and other biological processes. Molecular functions were mainly related to cytokine receptor binding, cytokine activity, receptor ligand activity, etc. The active ingredients were related to IL-17 signaling pathway, TNF and Influenza A signaling pathway, etc.  Conclusion  The possible active compounds of Jinzhen oral liquid could be anti-viral and anti-inflammatory that could have potential therapeutic effect against virus infection, lung injury and inflammation caused by SARS-CoV-2.
Prevention and treatment of COVID-19 with Traditional Chinese Medicine
YU Yaru, LU Pengfei, WANG Hongxia, HUANG Baokang
2020, 38(3): 202-206, 210. doi: 10.12206/j.issn.1006-0111.202003098
Abstract(8030) HTML (2810) PDF (536KB)(87)
Abstract:
The novel coronavirus pneumonia is an acute respiratory infectious disease mainly manifested by fever, fatigue and dry cough, caused by new coronavirus 2019-nCoV infection(COVID-19). Traditional Chinese Medicine played an important role in the prevention and treatment of COVID-19 during this breakout. This article reviews the clinical treatments of SARS-CoV-2 with TCM, the pathogenesis of COVID-19, dialectical treatment with TCM, and the antiviral, anti-inflammatory, immune regulatory effects of TCM. Some TCM with dual immuno-modulatory effects draw special attention, which may shed light on the prevention and treatment of COVID-19.
Clinical medication response under new major infectious disease: off-label use and compassionate use
LI Zhuman, GUO Zhijun, XU Feng
2020, 38(3): 207-210. doi: 10.12206/j.issn.1006-0111.202003035
Abstract(6723) HTML (1939) PDF (515KB)(38)
Abstract:
At present, there are no specific targeted drugs for the treatment of pneumonia (COVID-19) caused by the novel coronavirus (SARS-CoV-2). Interferon, lopinavir/ritonavir, ribavirin, chloroquine phosphate were chosen as off-label use, and remdesivir was chosen as compassionate use. This paper reviewed the behavior of the two medication response to the new major infectious disease.
Research progress on indanomycin natural products
ZHU Yuqin, WU Jiequn, SUN Peng
2020, 38(3): 211-215, 226. doi: 10.12206/j.issn.1006-0111.201910034
Abstract(7945) HTML (1734) PDF (928KB)(70)
Abstract:
Indanomycins are a class of secondary metabolites of microorganisms with a trans-tetrahydroindan (indane) ring. These compounds generally have good antibacterial, insecticidal and antitumor biological activities, which have caused wide interest for medicinal chemists and biologists. This review summarizes the research progress of the discovery, biological activity, chemical synthesis and biosynthesis of indanomycin compounds since 1979 and provides scientific reference for the research and development of indanomycin antibiotics.
Anti-inflammatory study on 9,9'-O-di-(E)-feruloyl-meso-5,5'-dimethoxysecoisolariciresinol (LCA), an active ingredient in Litsea cubeba (Lour.) Pers
YU Luyao, JIA Dan, SHEN Hui, SUN Xiaolei, QIN Luping, HAN Ting
2020, 38(3): 216-220. doi: 10.12206/j.issn.1006-0111.201912159
Abstract(7109) HTML (1601) PDF (735KB)(43)
Abstract:
  Objective  To evaluate the anti-inflammatory effects of LCA, which is the active component from Litsea cubeba (Lour.) Pers.  Methods  Pharmacodynamic evaluations of ear swelling and cotton ball granuloma models were used in animal experiments. In vitro experiment, lipopolysaccharide (LPS) stimulated monocyte macrophage RAW264.7 cells were used to evaluate the anti-inflammatory activity of LCA by detecting the secretions of nitric oxide (NO), tumor necrosis factor-α (TNF-α), the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein.  Results  In ear swelling experiment, the extent of ear swelling was significantly lower in the LCA treated group than the model group. The inhibition rate was greater in the high LCA concentration group than the positive drug group. In addition, LCA reduced the weight of cotton ball granuloma markedly. At the cell level, LCA significantly inhibited the secretions of NO, TNF-α and reduced the expressions of iNOS and COX-2 in LPS-stimulated RAW 264.7 cells.  Conclusion  LCA has significant anti-inflammatory effects in vitro and in vivo. The further studies are warranted for the development of anti-inflammatory drugs.
Improvement of impaired endothelial progenitor cell functions by in vitro drug interference in DOCA-salt hypertensive mice
SHANG Liuwenxin, SUN Xin, PENG Cheng, XIE Hehui, CHEN Fengyuan, ZHANG Chuan
2020, 38(3): 221-226. doi: 10.12206/j.issn.1006-0111.201912074
Abstract(5975) HTML (1204) PDF (1339KB)(21)
Abstract:
  Objective  To investigate the effect of tetrahydrobiopterin (BH4), superoxide dismutase-polyethylene glycol (PEG-SOD) and N(G)-nitro-L-arginine (L-NNA) on impaired endothelial progenitor cell (EPC) functions in DOCA-salt hypertensive mice.  Methods  DOCA-salt hypertension was created and systolic blood pressure was measured by tail-cuff methods. EPC was isolated from bone marrow of mice and characterized by flow cytometry and fluorescence microscopy. EPC of DOCA-salt mice was incubated with BH4, PEG-SOD, and L-NNA for 24 h, then in vitro EPC function assays were performed.  Results  Compared with control group, systolic blood pressure was significantly increased in DOCA-salt mice. Both EPC adhesion and angiogenesis functions were impaired in DOCA-salt mice compared to control animals, which were reversed by incubation with BH4, PEG-SOD and L-NNA.  Conclusion  BH4, PEG-SOD and L-NNA rescued the impairments from EPC functions in DOCA-salt hypertensive mice.
Identification of structural analogues xanthine, theophylline and theobromine by surface-enhanced Raman spectroscopy
CUI Xiaolin, LU Feng
2020, 38(3): 227-231, 258. doi: 10.12206/j.issn.1006-0111.202001005
Abstract(7741) HTML (1881) PDF (1218KB)(36)
Abstract:
  Objective  To distinguish the structural analogues xanthine, theophylline and theobromine by surface-enhanced Raman spectroscopy.  Methods  Concentrated silver colloid enhancement reagent was prepared as the Raman substrate to increase the number of "hot spots" per unit area, improve the sensitivity of surface-enhanced Raman spectroscopy, enhance the signal strength of the samples and achieve the effective discrimination of structural analogues. Meanwhile, the feasibility of surface-enhanced Raman spectroscopy in practical application was verified by determining serum samples of three mixtures.  Results  The concentrated silver colloid greatly increased the Raman intensity of the three structural analogues. The spectra of each individual compound and the mixture in the serum system was obtained. The detection limit of the three substances in aqueous solution were 0.005, 0.01 and 0.005 μmol/L respectively.  Conclusion  Surface-enhanced Raman spectroscopy is a potent technique for distinguishing structural analogues. It is rapid, sensitive and nondestructive to samples. Hence, it can be widely used in the fields of detection, analysis, clinical treatment and diagnosis.
The effect of four compounds of astragalus isoflavones on the differentiation of PC 12 cells
WU Qiuling, CHENG Yanqiong, LIU Aijun, ZHANG Weidong
2020, 38(3): 232-236. doi: 10.12206/j.issn.1006-0111.202001045
Abstract(7444) HTML (2155) PDF (937KB)(23)
Abstract:
  Objective  To investigate the effects of calycosin, formononetin, calycosin-7-glucoside and ononin on PC 12 cells differentiation.  Methods  PC 12 cells were cultured and treated with different concentrations of nerve growth factor (NGF), calycosin, formononetin, calycosin-7-glucoside and ononin for 5 days, once a day, 3 times in a row. The neurite outgrowth of PC 12 cells was observed and the expression of β III-tubulin were measured by immunofluorescence.  Results  Compared with the vehicle group, neurite outgrowth and the expression of β III tubulin in PC 12 cells had not promoted by calycosin, formononetin, calycosin-7-glucoside and ononin (0.01-10.00 μmol/L).  Conclusion  PC 12 cells differentiation could not be induced by calycosin, formononetin, calycosin-7-glucoside and ononin.
Pharmacokinetics of HMS-01 in rats
ZHANG Yu, QIN Zhen, SUN Yang, LÜ Jiaguo, WU Fang, LIU Xia
2020, 38(3): 237-240, 249. doi: 10.12206/j.issn.1006-0111.201907036
Abstract(9250) HTML (2278) PDF (547KB)(32)
Abstract:
  Objective  To study the pharmacokinetics of HMS-01 in rats and provide support for subsequent study.  Methods  A sensitive and specific method for the determination of HMS-01 in plasma and other biological samples was established by LC-MS/MS. The pharmacokinetics of HMS-01 in rats was studied by the established method. The pharmacokinetics of one dose of single intragastric administration and one dose of single intravenous administration in SD rats were studied, and the basic pharmacokinetic parameters were obtained.  Results  After intravenous injection of 1 mg/kg HMS-01, the area under the plasma concentration-time curve AUC0-t of male and female rats was 221 ng·h/ml and 409 ng·h/ml, respectively. The average clearance rates were 4.53 L/h·kg and 2.41 L/h·kg, respectively. The average plasma elimination half-lives were 0.786 h and 1.27 h, and the apparent distribution volume was 5.13 L/kg and 3.82 L/kg, respectively. After intragastric administration of 30 mg/kg HMS-01, the peak time of plasma concentration in rats was 1.17 h, the peak concentration of Cmax was 1 243 ng/ml, and the elimination half-life t1/2 was 2.00 h. The AUC0-t of male and female rats was 2 271 and 8 529 ng·h/ml respectively, and their bioavailability was 34.3% and 69.5% respectively.  Conclusion  The pharmacokinetics of HMS-01 in rats has significant gender differences. It is well absorbed orally, and the bioavailability of HMS-01 in females is much higher than that in males.
Inhibition of ebracteolatain A in the proliferation of breast cancer cells by interfering with PKD1-mediated MEK/ERK and PI3K/AKT signaling pathways
ZHOU Jin, LI Chengjian, TAN Fuli, YANG Xinying, ZHANG Xiaolin, ZHAO Liang
2020, 38(3): 241-244, 276. doi: 10.12206/j.issn.1006-0111.201912008
Abstract(5958) HTML (1865) PDF (780KB)(24)
Abstract:
  Objective  Breast cancer is one of the deadliest malignancies in the world. ebracteolatain A (EA) is a kind of acetylphloroglucinol extracted from ebracteolatain. To explore the specific mechanism of EA inhibiting the proliferation of breast cancer cell MCF-7, so as to provide a new approach for the clinical treatment of breast cancer.  Methods  EA with different concentrations were added to breast cancer cell MCF-7 to detect changes in PKD1 protein expression. The plasmid with overexpressed PKD1 was constructed and transfected into cells, and the mRNA and protein expression levels of PKD1 were detected by real-time fluorescence quantitative PCR and Western Blot assay. CCK-8 assay was used to detect changes in cell proliferation capacity. Western Blot assay was used to detect the expression level of PKD1 and its related signaling pathways.  Results  EA inhibited the expression of PKD1 protein in breast cancer cells with a dose-dependent manner (P< 0.05). When transfected with the overexpressed plasmid, PKD1 was significantly increased in mRNA and protein levels (P<0.001). At the same time, PKD1 overexpression significantly reversed inhibition of EA on MCF-7 proliferation (P<0.001). It was confirmed by signaling pathway analysis that EA might affect the proliferation ability of breast cancer cells by inhibiting PKD1-mediated MEK/ERK and PI3K/AKT signaling activity (P<0.05).  Conclusion  EA could inhibit the proliferation of breast cancer cells by regulating PKD1-mediated MEK/ERK and PI3K/AKT signaling pathways.
Determination of britanin content in different parts of Inula linariifolia Turcz by HPLC
LI Yubin, YE Ji, ZHANG Weidong
2020, 38(3): 245-249. doi: 10.12206/j.issn.1006-0111.202001049
Abstract(4643) HTML (1115) PDF (658KB)(39)
Abstract:
  Obejctive  To determine and compare britanin content in dried aerial parts and capitulum of Inula linariifolia Turcz from 7 different origins by HPLC.  Methods  Analysis was performed on Agilent Zorbax SB C18 (250 mm×4.6 mm, 5 μm). Acetonitrile and water were used as mobile phase for gradient elution at 1.2 ml/min. Column temperature was 30 ℃ and the detection wavelength at 212 nm.  Results  The results meet the requirements of the method validation in 2015 edition of Chinese Pharmacopeia. The average britanin content in dried aerial parts of Inula linariifolia Turcz is 0.125% vs 0.732% in capitulum, which is significantly different.  Conclusion  The established method is simple and convenient. It can be used for quality control of Inula linariifolia Turcz.
Rapid identification of chemical constituents in serum and plasma of Fuzheng Huayu capsules by UHPLC-TOF/MS
XING Xinrui, CAO Qi, CHEN Si, ZHU Zhenyu
2020, 38(3): 250-254, 267. doi: 10.12206/j.issn.1006-0111.201906027
Abstract(8314) HTML (2128) PDF (586KB)(51)
Abstract:
  Objective  To identify the blood components of Fuzheng Huayu capsule by ultra performance liquid chromatography-high resolution time-of-flight mass spectrometry (UHPLC-Q-TOF/MS).  Methods  ACQUITY UPLCHSS T3 (2.1 mm × 100 mm, 1.8 μm) was used to chromatographic separation; mobile phase was 0.1% formic acid aqueous solution (A) −0.1% formic acid acetonitrile solution (B). The gradient elution conditions included: 0−3 min, 2% B; 3−18 min, 2%−50% B; 18−22 min, 50%−95% B; 22−25 min, 95% B. The equilibration time was 10 min, the flow rate was 0.40 ml/min, and the analysis time was 25 min. The mass spectrometry was characterized by electrospray ionization by a positive-negative ion mode scan with a range of 100-1 100 m/z.  Results  49 components were identified in the serum samples at one time, of which 4 were positive and negative ion modes.  Conclusion  The blood components of Fuzheng Huayu capsule were clarified by this method, which enriched the scientific connotation of Fuzheng Huayu capsule, and laid the foundation for the in-depth study of the compound.
Study on the stability of the effective components cinnamic acid in the decoction of cinnamon
LI Qunying, LI Shengjian, XU Tianyi, XIELI Chunzi, ZHAO Liang, XU Qiuping
2020, 38(3): 255-258. doi: 10.12206/j.issn.1006-0111.202002002
Abstract(10200) HTML (1961) PDF (577KB)(275)
Abstract:
  Objective  To develop a high-performance liquid chromatography-diode array detector (HPLC-DAD) method for determination of cinnamic acid in the decoction of cinnamon, and investigate the effect of different storage temperature and time for the stability of cinnamic acid.  Methods  An HPLC- DAD method was established. Separation was performed on an Agilent Zorbax C18 column (4.6 mm×250 mm, 5 μm) with 0.1% formic-acetonitrile acid water solution (60:40) as the mobile phase by isocratic elution. The flow rate was 1.0 ml/min, the temperature of column was 25 ℃, the injection volume was 5 μl, the detective UV wave length was 275 nm. The decoction were stored under refrigerated temperature (4 ℃) ambient temperature (25 ℃) and high temperature (40 ℃). The cinnamic acid was detected after 0, 1, 3, 7, 14, 21, 30 d.  Results  Cinnamic acid was successfully separated by this method, with good linear relationship between 10.21-204.20 μg/ml. The precision, repeatability, stability and recovery were good. Compared with the zero day, the content of cinnamic acid in the decoction of cinnamon decreased significantly (P<0.01) after 21 days and 30 days of ambient temperature storage and after 14 days, 21 days and 30 days of high temperature storage, but no significant change was found in the other groups (P>0.05).  Conclusion  This HPLC-DAD method had good stability and repeatability. Cinnamic acid was stable in the decoction of cinnamon for 30 days under refrigerated temperature.
Research on the fingerprint and three active components assay in Shenshuaining granules by HPLC
SONG Xinhua, CHEN Xujiao, DENG Fengyi, GAO Shouhong, PENG Hui
2020, 38(3): 259-263. doi: 10.12206/j.issn.1006-0111.201911005
Abstract(6358) HTML (1587) PDF (591KB)(23)
Abstract:
  Objective  To establish the fingerprint spectrum and assay three active components (hesperidin, salvianolic acid B and chrysophanol) in Shenshuaining granule by HPLC method.  Methods  The chromatographic separation was achieved on SunFireTM C18 column with acetonitrile-0.1% formic acid aqueous solution as mobile phase. Gradient elution program was applied with flow rate of 1.0 ml/min, detection wavelength at 254 nm and the column temperature at 25 ℃. The fingerprint spectrum was established and three active components in Shenshuaining granule were assayed.  Results  There were 22 common peaks on the fingerprints after analyzing chromatograms from 10 batches of Shenshuaining granules. Good fingerprint similarities (≥0.9) between different batches and the control chromatogram were found. This method has great repeatability, stability and precision, which meets all the assay requirements.  Conclusion  A simple and reliable HPLC method was developed, which is suitable for the fingerprint establishment of Shenshuaining granules. It provides a method for the quality control of Shenshuaining granules.
Emodin assay in Ampelopsis radix by RP-HPLC
MENG Fei, SONG Xueli
2020, 38(3): 264-267. doi: 10.12206/j.issn.1006-0111.201911114
Abstract(4948) HTML (1013) PDF (582KB)(25)
Abstract:
  Objective  To establish a method for Emodin assay in Ampelopsis radix, and to improve the quality control of Ampelopsis radix.  Methods  Reversed phase high performance liquid chromatography was used. The column: Apollo-C18 (4.6 mm×250 mm, 5 μm); mobile phase: methanol:0.2% phosphoric acid (85:15); flow rate: 1.0 ml/min; column temperature: room temperature; detection wavelength: 220 nm.  Results  With the specified chromatographic conditions, there was a good linear relationship for Emodin in Ampelopsis radix in the range of 0.124-3.968 μg/ml. The linear regression equation was Y= 53 962X–966.46, r=0.999 7. The average recovery was 99.7%. RSD=2.5% (n=9).  Conclusion  This method is accurate, sensitive and repeatable. It is suitable for the determination of emodin in Ampelopsis radix.
Oxycodone versus sufentanil in patients undergoing laparoscopic gastrointestinal surgery
PU Jun, LI Yonghua, YANG Liye
2020, 38(3): 268-272. doi: 10.12206/j.issn.1006-0111.201912165
Abstract(6060) HTML (1812) PDF (671KB)(26)
Abstract:
  Objective  To compare the perioperative application of sufentanil and oxycodone in patients undergoing laparoscopic surgery for gastric or colorectal cancer.  Methods  59 patients were selected and randomly divided into group O and group S. Anesthesia was induced with sufentanil 0.3 μg/kg in group S and oxycodone 0.3 mg/kg in group O. Anesthesia was maintained with sevoflurane balanced anesthesia. When heart rate or blood pressure reached 20% over the baseline, additional dose of oxycodone 0.1 mg/kg was given in group O and sufentanil 0.1 μg/kg in group S. 30 minutes before the end of surgery, patients in group S received sufentanil 0.1 μg/kg and group O with oxycodone 0.1 mg/kg separately. Two hours in the PACU, a rescue dose of sufentanil 0.1 μg/kg or oxycodone 0.1 mg/kg was given to the patients with VAS score bigger than 4. Hemodynamic index, VAS score, Ramsay score, adverse responses and analgesics rescue were recorded.  Results  No difference was found in hemodynamic index, VAS score and analgesics rescue between the two groups (P>0.05). Ramsay score of group S is lower than that of group O (P=0.014). Induction period bucking incidence in group O was obviously lower than that in group S(P=0.002). The incidence of emergency agitation in group O was significantly lower than that in group S(P=0.045).There was no significant difference in respiratory depression, postoperative nausea and vomiting between two groups (P>0.05).  Conclusion  Compared with sufentanil, oxycodone significantly reduced the incidence of bucking and emergency agitation. Oxycodone provided better sedation to patients who received laparoscopic surgery for gastric or colorectal cancer.
Correlation analysis of valproic acid and its metabolites to hepatotoxicity
ZHOU Xun, CHEN Shun, ZONG Chuanfeng, GAO Shouhong
2020, 38(3): 273-276. doi: 10.12206/j.issn.1006-0111.201910080
Abstract(7557) HTML (2501) PDF (533KB)(46)
Abstract:
  Objective  To analyze the correlation of valproic acid and its metabolites (2-propyl-4-pentenoic acid, 3-hydroxy valproic acid,5-hydroxy valproic acid) with liver injury reference index.  Methods  328 plasma samples from epilepsy patients were collected and divided into two groups(123 samples from patients with abnormal liver function, experimental group; 205 samples from patients with normal liver function, control group).The plasma concentrations of valproic acid and its metabolites in the two groups were determined by LC-MS/MS method and the diagnostic value of the concentrations to liver disfunction was analyzed by ROC curve.  Results  The mean plasma concentration of valproic acid and its three metabolites in the patients with abnormal liver function was higher than that in the control group with was statistically difference(P<0.05).The concentration of valproic acid and its metabolites could be used as a reference for the diagnosis of liver injury,5-hydroxy valproic acid had better diagnostic value than valproic acid.  Conclusion  The metabolites of valproic acid were associated with hepatotoxicity, which could be used as a diagnostic index of liver injury and could be a reference for clinical safe application of valproic acid.
Bibliometrics analysis of community chronic disease management research based on literature co-occurrence analysis system
LIU Binglong, GE Qinan, MA Erli
2020, 38(3): 277-281. doi: 10.12206/j.issn.1006-0111.202002057
Abstract(5736) HTML (1413) PDF (552KB)(20)
Abstract:
  Objective  To investigate the current situation and existing problems of community chronic disease management in China and provide a theoretical basis for community chronic disease management to reduce the mortality and economic burden.  Methods  Research papers on community chronic disease management published in Chinese academic journal network from January 2010 to January 2020 were selected. Literature co-occurrence analysis system software, Bicomb2.0, and SPSS were used for data extraction and analysis based on publication years, geographical distribution, funding sources, etc.  Results  1 427 papers were included. Most papers were published in the recent three years (2017—2019), with an average of 206.7 papers per year. 1 347 papers in Chinese (94.4%) and 80 in English (5.6%) were published in 436 journals, and 24.5% were funded. Hot topics are community health services, health management, diabetes and hypertension management, influencing factors.  Conclusion  Community chronic disease management has drawn a lot of attention in China. Economically well-developed provinces invested more on community chronic disease management. Universities are the main research institutions. Most researches are still at the exploratory stage.
Application of TTI in quality control of the military thermo-sensitive drugs
WANG Boyang, LI Jie, GAO Jin, WANG Zidong
2020, 38(3): 282-285, 288. doi: 10.12206/j.issn.1006-0111.201912088
Abstract(6396) HTML (1905) PDF (627KB)(37)
Abstract:
To ensure the safety and efficacy of the military thermo-sensitive drugs, it is necessary to monitor the temperature changes through the whole process of production, transportation, storage, distribution and application. The characteristics of various commercial TTI were analyzed. The applications of TTI technology in the quality control for military thermo-sensitive drugs were reviewed in order to provide accurate quality assurance for those drugs.
2020, 38(3): 286-288. doi: 10.12206/j.issn.1006-0111.201911045
Abstract(6229) HTML (1746) PDF (484KB)(43)
Abstract: