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  • ZHOU Lipeng, LUO Xiaowei, WANG Shukai, CHANG Zihao, HU Qian, LIU Yuqi, GAO Ye, CHEN Yinxin, WANG Baojin, HUANG Ya, WANG Zhaohui, CUI Yitong, LIU Yue, ZHANG Lanzhen
    Chinese Pharmaceutical Journal. 2024, 59(2): 136-141.

    OBJECTIVE To study the chemical constituents of ethyl acetate extract from Moringa oleifera leaves. METHODS The chemical constituents of ethyl acetate extract from Moringa oleifera leaves were isolated and purified by chromatographic methods. The structures of isolated compounds were identified by MS and NMR data. DPPH and ABTS were used to test the antioxidant activities of the compounds in vitro. RESULTS Fourteen compounds were isolated from ethyl acetate extract of Moringa oleifera leaves and identified as icariside B1 (1), (3S)-O-β-D-glucopyranosyl-6-[3-oxo-(2S)-butenylideny]-1, 1, 5-trimethylcyclohexan-(5R)-ol (2), icariside B2 (3), 9-hydroxy-megastigma-4, 7-dien-3-one-9-O-β-D-glucopyranoside (4), tectorigenin (5), tectoridin (6), iristectorin A (7), iristectorin B (8), 5-hydroxy-2-hydroxymethylpyridine (9), androsin (10), 3, 4, 5-trimethoxyphenyl-1-O-β-D-glucopyranoside (11), 1-O-(4-hydroxymethylphenyl)-α-L-rhamnopyranoside (12), benzyl-O-β-D-glucopyranoside (13) and methyl 2-[4-(α-L-rhamnopyranosyl) phenyl] acetate (14), respectively. Among them, compounds 6, 7 and 8 had certain antioxidant activities, but the activities were weaker than that of vitamin C as positive control. CONCLUSION Compounds 2-11 are isolated from Moringa genus for the first time.

  • LIU Minyan, HE Jingyu, HE Qingguo, DONG Yan, ZHANG Huixin, SU Hongning
    Chinese Pharmaceutical Journal. 2024, 59(2): 142-150.

    OBJECTIVE To construct a multi-dimensional network system of “component-target-disease”, find the quality markers related to the efficacy of Shensong Yangxin capsules, and establish an efficient and rapid determination method. METHODS The pharmacodynamic substances selected by network pharmacology were used as quality markers and a novel HPLC-ESI-MS/MS method was developed. During the development of the method, multiple-reaction monitoring scanning and a multi-periods program were applied for quantification by switching electrospray ion source polarity between positive and negative modes at appropriate time points in a single run. Chromatographic separation was performed on a Waters C18 column with linear gradient elution of 0.1% formic acid aqueous solution and acetonitrile at a flow rate of 0.8 mL·min-1. RESULTS According to the results of network pharmacology, twenty compounds with high contribution were selected as quality markers for content determination. The results of methodological verification showed that all calibration curves had good linearity (r2>0.991 1) within the test ranges. The precision, accuracy and stability of the method were all satisfying. CONCLUSION The analytical method is simple, rapid, specific and reliable, which is useful for pharmacodynamic substance screening and comprehensive quality evaluation of Shensong Yangxin capsules.

  • DONG Degang, YANG yue, ZHENG Xianglong, MAO Wenli, SONG Mei, YAN Zhangren, WANG Wanchun
    Chinese Pharmaceutical Journal. 2024, 59(2): 151-160.

    OBJECTIVE To investigate the effect of 717 Jiedu decoction on neutrophil extracellular traps (NETs) and CYR61/CCN1 expression in local tissue of rats after Agkistrodon halys bite. METHODS SD rats were randomly divided into normal control group, Agkistrodon halys bite group and high-dose and low-dose 717 Jiedu decoction groups. The serum and thigh gastrocnemius were collected, and the pathological changes of gastrocnemius in each group were observed by Hematoxylin-Eosin staining(HE) and Masson staining, the ultrastructure of gastrocnemius in each group was observed by transmission electron microscopy, the apoptosis of gastrocnemius cells in each group was detected by TUNEL method, and the serum circulating-free cell (cf-DNA) level was detected by PicoGreen fluorescence. The expression levels of myeloperoxidase (MPO) in serum and gastrocnemius were detected by enzyme-linked immunosorbent assay(ELISA), the change of neutrophil elastase (NE) in gastrocnemius was detected by immunohistochemistry, and the level of citcitinic histone H3 (CitH3) in gastrocnemius was detected by immunofluorescence. The expressions of CYR61/CCN1 protein and its mRNA in gastrocnemius were detected by Western blot and PCR. RESULTS Compared with the normal group, the model group showed significant inflammatory infiltration and bleeding reaction, and the degree of collagen fibrosis increased. Ultrastructure showed that the structure of gastrocnemius cells in the model group was seriously damaged, and the distribution of muscle segments was asymmetrical. The contents of cf-DNA and MPO in serum were significantly increased (P<0.01), the protein expressions of MPO and CitH3 in gastrocnemius were increased (P<0.05 or P<0.01), and the protein and mRNA expressions of CYR61/CCN1 in gastrocnemius were up-regulated. All the administration groups of 717 Jiedu decoction significantly improved the local inflammatory response and bleeding symptoms of rats, reduced the degree of collagen fibrosis, effectively inhibited the apoptosis rate of gastrocnemius cells of pit viper bitten rats, and reduced the contents of cf-DNA and MPO in serum (P<0.05 or P<0.01). The expressions of NE and MPO in gastrocnemius were inhibited in the high-dose 717 Jiedu decoction group, and the expression of CitH3 in gastrocnemius muscle was decreased in all administration groups of 717 Jiedu decoction (P<0.05 or P<0.01), and the high expression of CYR61/CCN1 protein and its mRNA was inhibited. CONCLUSION The venom of Agkistrodon halys can induce the formation of neutrophil NETs in local tissue and the overexpression of CYR61/CCN1. The 717 Jiedu decoction could improve the ultrastructure of gastrocnemius muscle and inhibit cell apoptosis, which may also improve snitch symptoms by regulating the NETs-Cyr61/CCN1 pathway. The signaling molecules of NETs and CYR61/CCN1 are expected to be new targets for the prevention and treatment of local tissue damage caused by Agkistrodon halys venom.

  • QI Lemuge, YANG Zonghui, WEI Ziqi, DUAN Haijing, CHEN Honggang, JIN Ling, ZHANG Jinbao, ZHAO Wenlong
    Chinese Pharmaceutical Journal. 2024, 59(2): 161-171.

    OBJECTIVE To compare the anti-alcohol and liver-protecting effects of four ancient prescriptions, Baibei powder, Shigao decoction, Jupi decoction and Gegen powder, and explore the potential mechanisms of the four ancient prescriptions in the treatment of alcoholic liver disease (ALD). METHODS Rats were randomly divided into normal group, model group and drug administration groups, and the rat drunken model was prepared with 56° liquor. The rats in each administration group were given Chinese medicine decoction by gavage, and the normal group and the model group were given pure water by gavage. The drunken sleep time of rats was recorded, and the blood ethanol concentration and the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in serum and liver were measured. Network pharmacology method was used to analyze the effective components, key targets and signaling pathways of the four ancipent prescriptions in the treatment of ALD. RESULTS The four ancient prescriptions could significantly prolong the drunkenness time and shorten the sobering time of drunken model rats. Among them, Baibei powder could significantly increase the serum activities of ADH, ALDH and super-oxide dismutase (SOD) and improve triglyceride (TG) and glutathione (GSH) contents (P<0.05). Shigao decoction could significantly reduce the content of serum TG. Jupi decoction could significantly improve the serum GSH and malondialdehyde (MDA) content. Gegen powder could significantly reduce the concentration of blood ethanol, improve the activities of ADH, ALDH and SOD and the contents of TG, total cholesterol (TC), glutathione S-transferase (GST), GSH and MDA in the serum or liver (P<0.05 or P<0.01). The four prescriptions could reduce the degree of liver pathological damage and reduce the area of lipid droplets to varying degrees. Through the network pharmacology analysis, a total of 78 targets were screened out for the treatment of ALD by the four prescriptions. Among them, tumor necrosis factor (TNF), protein kinase B1(AKT1), estrogen receptor 1 (ESR1), epidermal growth factor receptor (EGFR), cytochrome P450 2C19(CYP2C19) and peroxisome proliferator activated receptorα (PPARα) could be used as important targets for the treatment of ALD. Kyoto encyclopedia of genes and gnomes pathway enrichment analysis showed that the ancient prescriptions may play a pharmacodynamic role through PPAR, AMP-activated protein kinase(AMPK), TNF/PPARα-CYP2E1-ALDH signaling pathway. CONCLUSION The four prescriptions all have certain anti-alcohol and liver protection effects, and the effect of Gegen powder is more significant. The four prescriptions may regulate key targets such as TNF, AKT1, cytochrome P450 2E1(CYP2E1), PPARα and ALDH by acting on the TNF/PPARα-CYP2E1-ALDH pathway, thereby accelerating alcohol metabolism, improving lipid metabolism, and reducing oxidative stress.

  • WAN Lingjuan, HE Hongjie, LI Jintian, FENG Xiaoli, LIU Xiaoxia, WEI Shuchang, WU Xiaoyu
    Chinese Pharmaceutical Journal. 2024, 59(2): 172-178.

    OBJECTIVE To investigate the effects of different drying methods on the concentrates of Astragalus membranaceus and provide a basis for the optimization and establishment of their drying processes. METHODS The contents of Astragalus methyloside, Pistil isoflavone glucoside, Pistil isoflavone, Mangiferin, Astragalus polysaccharide, ethanol extract and the clarity index and solubility index were used as evaluation indexes to dry Astragalus concentrate by freeze-drying, vacuum drying, atmospheric pressure drying and microwave drying, and the weights of each index were jointly determined by hierarchical analysis (AHP) and entropy weighting method, and the most suitable drying method was selected by the combination of comprehensive scoring, cluster analysis, fingerprinting and other methods as well as the characteristics of each drying method itself. RESULTS The effects of different drying methods on the concentration of Astragalus membranaceus varied widely, with the highest comprehensive scores for freeze-drying and vacuum-drying and lower scores for atmospheric-pressure drying and microwave drying. According to the analysis of similarity evaluation software, the fingerprint profiles of freeze-dried and vacuum-dried samples were the most similar to those of concentrates, the differences between the samples obtained from the two drying methods were small, and the results were similar to the comprehensive scores. Within the experimental range, the concentrates of Astragalus membranaceus were more stable under freeze-drying and vacuum-drying conditions. CONCLUSION The effect of different drying methods and conditions on Astragalus concentrates varies greatly. Through the study of four drying methods, vacuum drying is finally selected as the most suitable drying method for Astragalus concentrates.

  • XU Qinke, WEI Xuebing, LI Li, WEI Peng, GUO Zhaohui, SUN Ying
    Chinese Pharmaceutical Journal. 2024, 59(2): 179-185.

    OBJECTIVE To establish a method for the determination of 37 kinds of inorganic elements by microwave digestion and inductively coupled plasma mass spectrometer (ICP-MS), and to detect and analyze 37 kinds of inorganic elements in cistanches herba from different habitats, and to preliminatively explore the pollution distribution of various inorganic elements in cistanches herba from different habitats. METHODS Using nitric acid and hydrogen peroxide as digestion reagent, microwave digestion was used to pretreat the samples. The contents of 37 inorganic elements in cistanches herba were determined simultaneously by internal standard correction and external standard quantitative ICP-MS method. RESULTS In the curve range of 0.50-100 μg·L-1(Hg: 0.20-20 μg·L-1) showed a good linear relationship with the peak area (r≥0.997 4). The detection limits were 0.000 27-0.045 μg·L-1. The average recoveries were 76.5% to 110.0% at high, medium and low levels. RSD of precision and repeatability were lower than 4.8%. The detection rates of 5 harmful heavy metal elements (copper, lead, arsenic, mercury, cadmium) that need to be controlled by Chinese Pharmacopoeia (2015 edition) in 40 batches of cistanches herba were 27.5%, 7.5%, 82.5%, 0 and 100%, respectively. The detection rate of barium, manganese, rubidium and strontium in 40 batches of samples is 100%, and the content is much higher than other elements,there are obvious regional differences. CONCLUSION This method has high sensitivity, good reproducibility, reduced the inspection time and cost, and can simultaneously detect various inorganic elements in cistanches herba, providing data support for optimal cultivation, quality assurance and drug safety of cistanches herba.

  • HAN Qiang, ZHANG Lei, GONG Yinhua, ZHU Jianguo, XIE Cheng
    Chinese Pharmaceutical Journal. 2024, 59(2): 186-190.

    OBJECTIVE To explore the occurrence and characteristics of interstitial lung disease (ILD) induced by novel oral anticoagulants (NOACs) and provide references for clinical safe drug use. METHODS The case reports of ILD induced by NOACs published in PubMed, Embase, CNKI, Wanfang and VIP were searched from the establishment of each database to March 2023, and statistical analysis was conducted on relevant information and data. RESULTS A total of 11 male patients from 8 articles were identified and included in the analysis, including 5 cases of apixaban, 5 cases of dabigatran etexilate and 1 case of edoxaban. The age of the patients was 65-91 (79.6±7.1) years old. All patients suffered from dyspnea and were diagnosed with ILD after imaging examination, in which diffuse alveolar hemorrhage was relatively common. ILD was found from 3 days to 4 years after medication. After treatment including drug withdrawal, mechanical ventilation and methylprednisolone pluse therapy, 9 cases had good prognosis and 2 cases died of respiratory failure. CONCLUSIONS ILD could be induced by different NOACs. Attention should be paid to dyspnea and other symptoms at the early stage of treatment, and imaging examination should be performed when necessary. Once ILD was suspected to be caused by NOACs, withdraw in time and appropriate measures such as glucocorticoid should be taken.

  • ZHANG Qi, SUN Yaqi, GAO Jinglin, NIE Xuyang, FENG Zhangying, WANG Mingxia
    Chinese Pharmaceutical Journal. 2024, 59(1): 1-6.

    Anti-tumor drugs have high toxicity and adverse reactions. Liposome formulation can reduce drug toxicity and degradation of drug activity, which is a promising target vector. At present, the pharmacokinetic study of most anti-tumor drug liposomes mainly takes the total concentration as the index, but the free drugs are the part that really plays the pharmacological effect in vivo. So the separation and determination of the free drugs are very important. Sample pretreatment is a key step in the separation and extraction of free drugs after liposome administration. This article focuses on common detection methods, pretreatment methods and analysis examples, to provide reference for the establishment of analysis methods in vivo for anti-tumor drug liposomes.

  • ZHOU Fanxing, TOGN Minghui, LIU Juan, LI Rong, FANG aiqing, GUO Yingqiu, SHI Zhenping, LI Juan
    Chinese Pharmaceutical Journal. 2024, 59(1): 7-17.

    Animal medicine is one of the important sources of Chinese medicine for disease prevention and treatment. In recent years, its bioactive substances have been gradually discovered, especially the protein and peptide components, which are co-occurring substances in animal medicine, with good biological activities such as antibacterial, anticancer and antithrombotic. In this paper, it was selected animal sources such as toad, different families of earthworms and scorpion, which have been studied more frequently, and searched domestic and international databases to review the research data related to animal proteins and peptides from 1989 to the present, focusing on reviewing the composition, composition analysis and biological activities of the proteins and peptides of these animal sources, so as to provide a reference basis for further research and application of animal source proteins/peptides.

  • LIU Jingjing, ZHANG Zhongmou, DAI Zhong, YANG Jingfan, XU Beilei, KANG Shuai, MA Shuangcheng
    Chinese Pharmaceutical Journal. 2024, 59(1): 18-28.

    OBJECTIVE To establish a molecular identification method for the adulteration of Zaocys dhumnades in Chinese patent medicine. METHODS Eleven kinds of Chinese patent medicines containing Zaocys dhumnades and 15 kinds of Zaocys dhumnades and their adulterants were collected. The total genomic DNA was extracted from all samples, and the comparison and analysis of Zaocys dhumnades and its adulterants were conducted based on 12S gene fragments. The universal primer sequence, the specific primer sequence and the primers and probes used for fluorescence quantification of Zaocys dhumnades were designed according to the difference points. Different PCR methods were used to amplify the DNA of Zaocys dhumnades contained in the medicinal materials of Zaocys dhumnades and Chinese patent medicines respectively. The reaction system was optimized and the tolerance and adaptability of the methods were investigated. RESULTS The specific PCR technique of Zaocys dhumnades was established. All the authentic Zaocys dhumnades had a clear band around 200 bp, and other adulterants had no band. Fluorescent quantitative PCR method was established for the identification of Chinese patent medicines with low DNA content. CONCLUSION The medicinal materials of Zaocys dhumnades can be effectively identified by PCR amplification with specific primers. Fluorescent quantitative PCR detection can effectively identify the authenticity of Zaocys dhumnades in Chinese traditional medicine.The method is specific, rapid and sensitive, which provides a reference for the identification of Zaocys dhumnades in Chinese patent medicine.