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Objective:To explore the reasonable combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma in treatment of cerebral malaria and investigate its mechanism based on network pharmacology. Method:The traditional Chinese medicine systems pharmacology database and analysis platform （TCMSP） and SymMap were used to obtain all the chemical components of Artemisiae Annuae Herba and Chuanxiong Rhizoma and the action targets were screened to construct a component target protein-protein interaction （PPI） network. Target genes related to cerebral malaria were collected with use of GeneCards and DisGeNET databases. Common targets were screened by overlapping drug targets and disease targets， and protein-protein interaction network analysis was performed to get key targets. Gene ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were carried out to get main signaling pathways. Furthermore， the classical experimental cerebral malaria mouse model was used to detect survival curve， protozoanemia level， survival rate， experimental cerebral malaria （ECM） coma and behavior scores. RayBio<sup>®</sup> cytokine antibody array was used to detect the expression level of cytokines in tissues and experiment was conducted for verification. Result:After combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma， 23 active ingredients， 179 drug targets， and a total of 100 common targets of the drug and disease were obtained. GO functional analysis identified 59 items （<italic>P</italic><0.05）， involving cytokine activity， growth factor activity， immune response， etc. KEGG pathway analysis revealed 51 related signaling pathways. The experimental results showed that the combined use of Artemisiae Annuae Herba and Chuanxiong Rhizoma could significantly improve the clinical signs of ECM mice， such as survival state， coma and behavioral scores. In the detection of expression levels of related cytokines in mice， the expression levels of <italic>γ-</italic>interferon （IFN-<italic>γ）</italic>， interleukin-10 （IL-10）， IL-4， and IL-1<italic>β</italic> in the compatible drug combination drug were significantly higher than those in the model group （<italic>P</italic><0.05）， which was consistent with the overlapping core targets predicted by network pharmacology. Conclusion:Based on the network pharmacology analysis and<italic> in vivo</italic> experiment verification， this study confirmed the synergistic effect of the combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma in the treatment of cerebral malaria， providing clear direction for further mechanism research， and a new possibility for the clinical intervention of cerebral malaria.
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Artemisiae Annuae Herba is a traditional Chinese medicine for clearing deficiency and heat. It is the only natural source of artemisinin, which is a specific antimalarial drug, and has been widely concerned all over the world. In addition to artemisinin, Artemisiae Annuae Herba also contains many sesquiterpenes, coumarins, flavonoids, volatile oils, polysaccharides and other chemical components, which show antipyretic, anti-inflammatory, antiviral microorganisms, anti-asthma, anti-oxidation, anti-tumor and other pharmacological activities. In addition to their own pharmacological activities, some components could enhance the antimalarial activity of artemisinin through different mechanisms at absorption and metabolism in vivo. In order to understand the pharmacokinetic characte-ristics of the chemical constituents contained in Artemisiae Annuae Herba and provide reference for the full development and clinical utilization of Artemisiae Annuae Herba resources in China, this present paper systematically collated the modern research literatures, and summarized the biosynthesis, in vivo analysis and pharmacokinetics of the chemical constituents in Artemisiae Annuae Herba.
Subject(s)
Antimalarials , China , Drugs, Chinese Herbal , Medicine, Chinese Traditional , Oils, VolatileABSTRACT
Objective: To study the constituents from the dried aboveground part of Artemisia annua. Methods: The chemical constituents were isolated by various chromatographic techniques and their structures were elucidated by spectroscopic analyses and comparison of NMR data with those reported in literatures. Results: Six compounds were obtained and characterized as artelignan (1), scopoletin (2), scoparone (3), chrysosplenol B (4), jaceidin (5) and mikanin (6). Conclusion: Compound 1 is identified as a new compound named artelignan.
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Objective: To study and create the algorithm for the diversity (AD) of extensible markup language (XML) tree map, and provide a new tool for the identification of Artemisiae Annuae Herba. Method: According to the literature research, the key information of Artemisiae Annuae Herba was selected from the macroscopic, mesoscopic and microscopic information, etc. Based on the key information, the relevant upper standards of domestic and foreign professional fields were cited to assign the unique identification independent of language for each data element, and the coding rules of relevant data elements were established. The digital coding technology was applied to the flexible structure editor, and the tree map was created, which could be returned as the 5th version of hypertext markup language (HTML5) or XML format. Based on the diversity related algorithms, the authors innovatively developed the AD of XML tree map of Artemisiae Annuae Herba, which took into account both of topology and semantics, and the expression model of related mathematical functions of Artemisiae Annuae Herba was established. By comparing the calculation results with the reality, the algorithm model was debugged continuously until the convergence of the core-culvert algorithm model. Result: Through the research on AD, the diversity between two XML tree maps could be calculated, and the discrimination or identification model of Artemisiae Annuae Herba also could be finally optimized and established. After calculation and analysis of the tested tree maps, the effective rate of the model was 100%. Conclusion: In this study, the establishment of the AD of XML tree map can effectively assist in the identification of Artemisiae Annuae Herba, which provides certain technical support and theoretical guidance for the research on intelligent application of traditional Chinese medicine.
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Artemisiae Annuae Herba is dry aboveground part of Artemisia annua, which has a long history of application in China. Modern research achievements make it shiny all over the world. The breakthrough in modern research also attracts a lot of attention and related research, and now a lot of achievements have been made. In order to perform further research purposefully, systematic review of existing achievements was made to understand industry pattern and development prospect. And the patent document is one of the important science and technology literature source. The patent information was collected from several special patent database, and the patent and industrial structure in the field comprehensively was analyzed with the aid of computer science, including life cycle, geographical distribution, international exchange, efficacy preferences, compatibility strategy, excellent application institutions, and high value patents. The result shows that the field has sizable development space, which should make use of the analysis result of the paper to formulate development strategies in line with our own.
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Objective: The calibration models were developed in the concentration of alcohol precipitation proee for Artemisiae Annuae Herba (AAH) and Lonicerae Flos (LF) in Reduning Injection (RI) to realize the on-line monitoring of production process. Methods: Based on the near infrared reflectance spectroscopy (NIRS), partial least regression (PLS) models were developed to fast measure the contents of neochlorogenic acid, chlorogenic acid, and 4-O-caffeoylquinic acid in the concentration of the alcohol precipitation proee for AAH and LF. Results: In the quantitative models of neochlorogenic acid, chlorogenic acid, and 4-O-caffeoylquinic acid, the coefficient of determination (R2) of cross validation sets were 0.954 5, 0.975 2, and 0.969 1; The root mean square errors of calibration (RMSEC) were 0.213, 0.676, and 0.225; The root mean square errors of cross-validation (RMSECV) were 0.233, 0.692, and 0.258. When the established models were applied to on-line monitoring, the coefficient of determination of neochlorogenic acid, chlorogenic acid, and 4-O-caffeoylquinic acid were 0.984 2, 0.983 7, and 0.987 0, the residual predictive deviation (RPD) were 4.77, 5.29, and 4.37; The relative standard errors of prediction (RSEP) were 3.519%, 3.778%, and 3.895%. Conclusion: The models above are proved to fast measure the contents of neochlorogenic acid, chlorogenic acid, and 4-O-caffeoylquinic acid in the concentration of alcohol precipitation proee for AAH and LF in RI.
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Objective:To study the application of statistical process control technology to establish the real-time release criteria of alcohol precipitation process of ArtemisiaeAnnuae Herba and Lonicerae Flos. Methods: Twenty-ninebatches of samples came from alcohol precipitation process of ArtemisiaeAnnuae Herba and Lonicerae Flos were collected as the calibration set. The contents of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, and solid content were determined to establish the quantitative real-timerelease criteria based on statistical process control technology. Thirteenbatches of alcohol precipitation process of ArtemisiaeAnnuae Herba and Lonicerae Flos were prepared under the different process conditions by the central composite design. They were regarded as the validation set to test the dependability of the real-time release criteria. Results: The established quantitative release ranges were neochlorogenic acid 0.279-0.541 mg/g, chlorogenic acid 1.941-2.610 mg/g, cryptochlorogenic acid 0.453-0.570 mg/g, and solid content3.565%-4.925%. The four index component contentsof the samples 1, 4, 8, 9, and 10 from the validation set werewithin the range of the real-time release criteria. Conclusion: Univariate statistical process control could be well monitored and understood of production process for Chinses materiamedica.They are used to achieve the purpose of real-time release.
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Artemisiae Annuae Herba has used as a medicine for more than 2 000 years. To infer based on the modern study results, Artemisiae Annuae Herba used for the treatment of malaria recorded in Zhou Hou Bei Ji Fang before 1 700 years should come from Artemisia annua. Based on the data of Chinese materia medica, from the field of treatment hotness and preventing attack of malaria etc., the Dao-di producing district of Artemisiae Annuae Herba should at Jingzhou (now Hubei) and surrounding areas in history. From the view of anti-malaria components artemisinin content, the Dao-di growing producing district of Artemisiae Annuae Herba should locate at Chongqing, Guangxi and its surrounding provinces. The study results showed that A. annua was harvested in flower bloom at autumn, and in this time it also had higher artemisinin content. If A. annua was stored exceed six months, artemisinin could be degraded about thirty percent. So it should be stored in a cool and dry place generally. Wild A. annua had a rich genetic diversity. Artemisinin content of A. annua breeding in experimental field could reache to two percent.
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To optimize the alcohol precipitation process for Lonicerae Flos and Artemisiae Annuae Herba (LA) in Reduning Injection and obtain the relationship equation of the key process parameters and quality attributes, which could provided a theoretical basis of the control automization in the alcohol precipitation process. With the transfer rates of neochlorogenic acid, chlorogenic acid, cryptochlorogenin acid, caffeic acid, secoxyloganin and solid content in precipitation liquid as evaluation indexes, the effect of the seven factors, such as relative density and the temperature of LA in liquid phase before alcohol precipitation, alcohol concentration in the end of alcohol precipitation, stirring speed in alcohol precipitation, adding alcohol speed, standing temperature, and standing time, on the alcohol precipitation process was investigated by the single factor experiment. By analysis of variance, the key factors that could influence the alcohol precipitation process were determined. Then the range of parameters of key factors was further studied and explored by Box-Behnken response surface methodology. The optimum preparation conditions of the alcohol precipitation process of LA were as follows: stirring speed was 550 r/min, adding alcohol speed was 4.0 mL/s, standing temperature was 30℃, standing time was 24 h, alcohol concentration was 75%, the relative density of LA was 1.10, and the temperature of LA was 25℃. Under these conditions, the transfer rates of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, caffeic acid, and secoxyloganin were 94.8%, 97.6%, 97.4%, 97.2%, and 96.1%, and the solid content was 4.2%. The alcohol precipitation process of LA have been optimized by the response surface method, which could help to enhance the stability of the process.
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Objective: Near-infrared (NIR) spectroscopy was used to rapidly determine the concentration of chlorogenic acid (CA) and soluble solid content in alcohol precipitation of Lonicerae Japonicae Flos and Artemisiae Annuae Herba (LA) in Reduning Injection, so as to increase the level of quality control of alcohol precipitation process. Methods: The LA samples of alcohol precipitation were collected. The PLS algorithm was used to establish NIR models between spectra and concentration of CA and total solid content, and the concentration of CA and soluble solid content in unknown batch were predicted. Results: The correlation coefficients (R) of NIR models were above 0.980 in calibration sets. The R of verification model was above 0.980, the root mean square error of prediction (RMSEP) for CA and soluble solid content were 0.541 and 0.218, respectively, and the relative standard errors (RSEP) for CA and soluble solid content were no more than 8%. Conclusion: The results demonstrate that NIR could determine the concentration of CA and soluble solid content in alcohol precipitation of Reduning Injection rapidly and accurately.