Systematic chemical characterization of Xiexin decoctions using high performance liquid chromatography coupled with electrospray ionization mass spectrometry / 中国天然药物

Xiexin decoctions (XXDs) display beneficial anti-inflammatory and anti-diabetic effects, which raises interests on this group of formulae for broad clinical applications. However, there was no report about systematic analysis of XXDs to elucidate the constitution of chemical components, which hampers further investigations on the therapeutic values of XXDs. In this work, crude herbs were extracted and prepared to obtain the XXDs for systemic analysis on their chemical compositions, according to the information described in the ancient Zhang Zhongjing's herbal formulae. LC-MS analysis of five XXDs was carried out to facilitate recognition of the source herbs for compounds in the mixture. A total number of 93 compounds were identified through our methods and their chemical classes encompassed five major groups, including protoberberine alkaloids, flavonoids, stilbenes, anthraquinones and saponins. Our current work provided important information about material basis for pharmacological studies on XXDs and would help shed light on relationships between chemical compositions and therapeutic effects.

Danshen-Chuanxiongqin Injection attenuates cerebral ischemic stroke by inhibiting neuroinflammation via the TLR2/ TLR4-MyD88-NF-κB Pathway in tMCAO mice / 中国天然药物

Danshen-Chuanxiongqin Injection (DCI) is a commonly used traditional Chinese medicine for the treatment of cerebral ischemic stroke in China. However, its underlying mechanisms remain completely understood. The current study was designed to explore the protective mechanisms of DCI against cerebral ischemic stroke through integrating whole-transcriptome sequencing coupled with network pharmacology analysis. First, using a mouse model of cerebral ischemic stroke by transient middle cerebral artery occlusion (tMCAO), we found that DCI (4.10 mL·kg

Mechanism of Xuanfei Baidu Tang in treatment of COVID-19 based on network pharmacology / 中国中药杂志

The study aimed to investigate the multi-constituent, multi-target mechanism of Xuanfei Baidu Tang(XFBD) in the treatment of coronavirus disease 2019(COVID-19), through exploring the main ingredients and effective targets of XFBD, as well as analyzing the correlation between XFBD targets and COVID-19. The compounds of each herb in XFBD were collected from TCM-PTD, ETCM, TCMSP and SymMap database. Next, the information of meridian tropisms was collected from Chinese Pharmacopoeia(2015 edition), and the target information of the major constituents of XFBD were obtained from TCM-PTD, ETCM, TCMSP and TargetNet database. Subsequently, the target network model and the major modules were generated by Cytoscape, and the functional enrichment analysis of XFBD targets were completed by DAVID and STRING. As a result, ten of the 13 herbs in XFBD belonged to the lung meridian, and 326 of the 1 224 putative XFBD targets were associated with the disease target of COVID-19, among which 109 targets were enriched in the disease pathways of viral infection and lung injury. The main biological pathways regulated by the key XFBD targets included viral infection, energy metabolism, immunity and inflammation, parasites and bacterial infections. In conclusion, the therapeutic mechanism of XFBD in COVID-19 showed a multi-herb, multi-constituent, multi-target pattern, with lung as the chief targeted organ. By regulating a series of biological pathways closely related to the occurrence and development of diseases, XFBD plays a role in balancing immunity, eliminating inflammation, regulating hepatic and biliary metabolism and recovering energy metabolism balance.

Analysis of chemical constituents in Shenmai Injection by LC-Q-TOF-MS and LC-IT-MS / 中国中药杂志

The chemical constituents in Shenmai Injection(SMI) were qualitatively analyzed by using liquid chromatography/quadrupole time-of-flight mass spectrometry(LC-Q-TOF-MS) and liquid chromatography-ion trap-mass spectrometry(LC-IT-MS). The analysis was performed on an Agilent Zorbax SB-C_(18)(4.6 mm×250 mm, 5 μm) and gradient elution was carried out with 0.05% formic acid solution-acetonitrile as mobile phase at a flow rate of 0.6 mL·min~(-1) and a column temperature of 30 ℃. Mass spectrometry data of the components in SMI were collected in negative ion mode. The structures of components were speculated and identified by analyzing mass spectrometry data, comparing with standards, and referring to related literature. A total of 64 components in SMI were estimated, and the structures were confirmed in 16 of them by comparison with standards. Fifty-six compounds derived from Ginseng Radix et Rhizoma Rubra included 34 protopanaxadiol ginsenosides, 19 protopanaxatriol ginsenosides, 1 oleanane ginsenosides and 2 other glycosides. Eight compounds derived from Ophiopogonis Radix included 7 steroidal saponins, and 1 monoterpene glycoside. The results of this study would provide an important theoretical basis for the improvement of the quality control standards and the discovery of effective constituents in SMI.

Intelligent and lean manufacturing for Chinese medicine:theory and its applications / 中国中药杂志

To cope with the " six major scientific problems" and the " five major technical challenges" of intelligent manufacturing and lean production of Chinese medicine( CM),we systematically proposed strategies,methods and the engineering theory of intelligent and lean manufacturing for CM by integrating the holistic view of traditional Chinese medicine and the concepts inspired from international advanced pharmaceutical technology. Moreover,the translational research of the theory and methods was successfully applied to six CMs such as Xuesaitong Injection. Several intelligent production lines were designed and built on the basis of the theory and methods,which greatly accelerated the digitalization,networking,and intelligence manufacture for CM. As a conclusion,the theory and applications provide technical demonstration for technical upgrading and high-quality development of CM industry.

UPLC fingerprint combined with quantitative analysis of multi-components by single marker for quality assessment of Danshen Injection / 中国中药杂志

Testing and analysis of chemical markers is currently the prevailing approach for quality assessment of traditional Chinese medicines. However,several important issues remain to be addressed,including the trade-off between accuracy and coverage. In this study,in order to give full play to the advantages of their respective methods and provide technical support for more comprehensively and rapidly evaluate the quality of Danshen Injection products,a fingerprint method was coupled with quantitative analysis of multicomponents by single marker( QAMS),with Danshen Injection as the carrier. Ultra performance liquid chromatography( UPLC) was used to establish the quantitative fingerprint. The UPLC fingerprints contained 13 common peaks,11 of which were identified by using ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry( UPLC-QTOF-MS). Furthermore,with sodium danshensu as the internal reference substance,relative correction factors( RCFs) of protocatechuic aldehyde,caffeic acid,rosmarinic acid,lithospermic acid,and salvianolic acid B were calculated through slope analysis method,and the QAMS method was adopted to determine the contents of these 6 components. The UPLC fingerprint was employed to assess the consistency of 12 batches of Danshen Injection,which showed good batch-to-batch consistency with similarity higher than 0. 99. In the comparison of contents of the six constituents obtained by QAMS and external standard method( ESM),RSD was all less than 4. 3%,indicating the good accuracy of the QAMS method. The QAMS method developed in this study combined with UPLC fingerprint can comprehensively reflect the internal quality of Danshen Injection when only the reference substance sodium danshensu is consumed,with greatly reduced detection cost and time. It provides a technical basis for further improving the quality standard of Danshen Injection.

Research progress of 5-hydroxymethylfurfural, a safety-related substance in traditional Chinese medicine injections / 中国中药杂志

Screening out the safety-related substances and establishing the corresponding standard has been a key research issue to improve the safety of traditional Chinese medicine injections(TCMIs). 5-HMF which widely exists in sugar-containing TCMIs has long been considered as an important safety-related substance. In this review, we summarizes the research progress on the toxicology of 5-HMF as well as the content and standards of 5-HMF in TCMIs.Therein, both literature summary and analysis results indicate that there are lack of toxicology researches of 5-HMF and its metabolites in TCMIs, although the potential toxicity of 5-HMF and its metabolites has been reported. Moreover, the content of 5-HMF largely varies from TCMIs to TCMIs, and even in the same TCMIs from different factories. To ensure the clinical efficacy of TCMIs, it urgent to carry out the study of the toxicology of 5-HMF in TCMIs comprehensively and systematically, so as to set up a relatively uniform standard as well as to develop process quality control method.

Development and application of component-based Chinese medicine theory / 中国中药杂志

Traditional Chinese medicine (TCM) prescription is the main therapies for disease prevention and treatment in Chinese medicine. Following the guidance of the theory of TCM and developing drug by composing prescriptions of TCM materials and pieces, it is a traditional application mode of TCM, and still widely used in clinic. TCM prescription has theoretical advantages and rich clinical application experience in dealing with multi-factor complex diseases, but scientific research is relatively weak. The lack of scientific cognition of the effective substances and mechanism of Chinese medicine leads to insufficient understanding of the efficacy regularity, which affects the stability of effect and hinders the improvement of quality of Chinese medicinal products. Component-based Chinese medicine (CCM) is an innovation based on inheritance, which breaks through the tradition of experience-based prescription and realize the transformation of compatibility from herbal pieces to components. CCM is an important achievement during the research process of modernization of Chinese medicine. Under the support of three national "973" projects, in order to reveal the scientific connotation of the prescription compatibility theory and develop innovative Chinese drugs, we have launched theoretical innovation and technological innovation around the "two relatively clear", and opened up the research field of CCM. CCM is an innovation based on inheritance, breaking through the tradition of experience based prescription, and realizing the transformation from compatibility of herbal pieces to component compatibility, which is an important achievement of the modernization of traditional Chinese medicine. In the past more than 10 years, with the deepening of research and the expansion of application, the theory and methods of CCM and efficacy-oriented compatibility have been continuously improved. The value of CCM is not only in developing new drug, more important is to build a communication bridge between traditional Chinese medicine and modern science and construct the system of key technologies which meet the need of innovation and development of TCM. This paper focused on the research progress, related concepts and technology development of CCM, as well as its application prospect in the theory research of Chinese medicine, development of innovative Chinese drugs, secondary development of Chinese patent medicine and upgrading of pharmaceutical technology.

Dissecting functional chemome of Xiaoqinglong decoction analogous formulae using network formulaology approach / 中国中药杂志

Analogous formulae (AF) refer to a set of traditional Chinese medicine (TCM) formulae sharing similar herbs and/or indications. Dissecting functional chemome of analogous formulae could enhance the understanding of the intrinsic nature of TCM. In this study, taking 5 Xiaoqinglong decoction analogous formulae (XQL AF) including Xiaoqinglong decoction, Mahuang Xingren Shigao Gancao decoction, Mahuang Fuzi decoction, Houpu Mahuang decoction and Daqinglong decoction as example, we systematically investigated the relationship between compounds and indications using network formulaology approach. The functional chemome of XQL AF were revealed by network analysis and molecular docking. This successful application in XQL AF suggests network formulaology could be a useful tool for AF-related research and therefore provide a new way to discover the scientific foundation of Zhang Zhongjing's herbal formulae.

Toxicogenomics and its application in safety evaluation of traditional Chinese medicine / 中国中药杂志

Toxicogenomics (TGx) refers to a set of technologies that assess genome-wide responses after toxic agent exposure. Altered gene expression patterns that are caused by specific exposures reveal how toxicants may disrupt cellular processes and lead to side effects. Development and application of " omics" technology facilitate the toxicogenomic research which sharing and interpretation of the enormous amount of biological information generated in toxicologic field. In recent years TGx has been widely valued and successfully applied as an effective research tool to evaluate the toxic effects of traditional Chinese medicine (TCM). Here we reviewed current progress in the field of TGx and focused on its application in traditional Chinese medicine safety evaluation, especially in revealing the mechanism, finding potential toxic biomarkers and studying compatibility detoxification of TCM.

Network formulaology: a new strategy for modern research of traditional Chinese medicine formulae / 中国中药杂志

This paper briefly analyzed and discussed the current status and major scientific challenges of traditional Chinese medicine (TCM) formulaology research. To promote formulaology research, a new strategy and corresponding technology, network formulaology, were proposed to reveal the complex interaction between functional chemome and biological responses network. The research framework and directions of network formulaology were also summarized and prospected.

Identification of phenylpropanoids in ciwujia injection by HPLC-MS / 中国中药杂志

There are reports about the chemical compounds of Ciwujia herbs, but with no study report about the chemical material basis of Ciwujia injection (CWJI). In this study, LC-MS(n) and LC-Q-TOF-MS techniques were adopted for a qualitative analysis on phenylpropanoids in CWJI. The Ultmate XB-C18 column (4.6 mm x 250 mm, 5 microm) was adopted and eluted with the mobile phase of 0.5% formic acid-water and acetonitrile, with the flow rate at 0.8 mL x min(-1) and the column temperature at 20 degrees C. Based on the data of high-resolution and multi-stage MS, control products and literatures, altogether 54 phenylpropanoids were identified in Ciwujia Injection, including 34 phenylpropanoids, 16 ligans and 4 coumarins. Among them, 28 were reported for the first time in Ciwujia, and 14 compound structures were identified in comparison with the control products. The method established in this study could be used to simply and rapidly identify phenylpropanoids in CWJI. The findings provide scientific data for defining the chemical material basis of CWJI.

Multi-objective optimization of extraction process for red ginseng based upon extraction efficiency and cost control / 中国中药杂志

It is the objective of this study to optimize the extraction process of red ginseng to minimize the unit cost of extracting effective ingredients. The relation between the target variables of total quantity of ginsenosides and first extraction time, first extraction solution amount, second extraction time, second extract solution amount were studied with Box-Behnken experimental design method. At the same we also considered the cost of extraction solution and energy usage. The objective function was set as unit cost of target (total quantity of ginsenosides or its purity) for the multi-objective optimization of extraction process. As a result, the optimal process parameters were found as first extraction time (108.7 min), first extraction solution amount folds (12), second extraction time (30 min), second extraction solution amount folds (8) to minimize the unit cost. It indicated that this approach could potentially be used to optimize industrial extraction process for manufacturing Chinese medicine.

Reliability theory based on quality risk network analysis for Chinese medicine injection / 中国中药杂志

A new risk analysis method based upon reliability theory was introduced in this paper for the quality risk management of Chinese medicine injection manufacturing plants. The risk events including both cause and effect ones were derived in the framework as nodes with a Bayesian network analysis approach. It thus transforms the risk analysis results from failure mode and effect analysis (FMEA) into a Bayesian network platform. With its structure and parameters determined, the network can be used to evaluate the system reliability quantitatively with probabilistic analytical appraoches. Using network analysis tools such as GeNie and AgenaRisk, we are able to find the nodes that are most critical to influence the system reliability. The importance of each node to the system can be quantitatively evaluated by calculating the effect of the node on the overall risk, and minimization plan can be determined accordingly to reduce their influences and improve the system reliability. Using the Shengmai injection manufacturing plant of SZYY Ltd as a user case, we analyzed the quality risk with both static FMEA analysis and dynamic Bayesian Network analysis. The potential risk factors for the quality of Shengmai injection manufacturing were identified with the network analysis platform. Quality assurance actions were further defined to reduce the risk and improve the product quality.

Dynamic predictive modeling of extraction process for red ginseng using near-infrared spectroscopy / 中国中药杂志

It is the objective of this study to develop dynamic predictive model for the extraction process of red Ginseng using NIR spectroscopy. NIR spectroscopy was collected online and PLSR models were developed for total quantity of ginsenosides. The performance of NIR prediction model achieved R, RMSEC, RMSEP of 0.996 09, 0.018 9, 0.016 8, respectively. A first order dynamic mass transfer model was combined with NIR prediction of the quality indicator to predict the trajectory of the extraction process based upon the initial 3 or 4 data points. The results showed good agreement with actual measurements indicating reasonable accuracy of the predictive model. It could potentially be used for advanced predictive control of the extraction process.

Network pharmacology study of mechanism on xuesaitong injection against retinal vein occlusion / 中国中药杂志

Retinal vein occlusion (RVO) is a common clinical disease causing vision loss. Risk factors such as diabetes, atherosclerosis are closely associated with RVO. Xuesaitong injection is used extensively in clinical treatment of RVO, however the mechanism is still unclear. In this study, we investigated the protective effect of Xuesaitong injection on RVO rat model. Using a compound-target network of Xuesaitong on anti-RVO constructed by literature mining, we aim to elucidate the multi-compound, multi-target effect of Xuesaitong injection. Fifteen potential targets of Xuesaitong injection associated with inflammation, angiogenesis, apoptosis, and coagulation were identified in this study. VEGF, IL-1beta and IL-6, three important targets in the compound-target network were further experimentally validated. This study provided experimental evidence for Xuesaitong injection being effective in treating RVO and a network view on its anti-RVO mode of action through a multi-compound and multiple-target mechanism.

Data integration, data mining and visualization analysis of traditional Chinese medicine manufacturing process / 中国中药杂志

Huge amount of data becomes available from the pharmaceutical manufacturing process with wide application of in- dustrial automatic control technology in traditional Chinese medicine (TCM) industry. The industrial big data thus provides golden op- portunities to better understand the manufacturing process and improve the process performance. Therefore it is important to implement data integration and management systems in TCM plants to easily collect, integrate, store, analyze, communicate and visulize the data with high efficiency. It could break the data island and discover useful information and knowledge to improve the manufacturing process performance. The key supporting technologies for TCM manufacturing and industrial big data management were introduced in this paper, with a specific focus on data mining and visualization technologies. Using historic data collected from a manufacturing plant of Shengmai injection of SZYY group, we illustrated the usefulness and discussed future prospects of data mining and visualization technologies.

Strategy and core technologies for the secondary development of Chinese patent medicine / 中国中药杂志

Secondary development of Chinese Patent Medicine (CPM) is an effective and innovation-driven way for the leaping development of Chinese medicine industry with less investment and faster return. Aim to improving the efficacy, safety and batch-to-batch consistency of CPMs, the theory and methodology for the secondary development of CPMs, mode for cultivating superior CPM, approaches to reforming the pharmaceutical technology and the corresponding core technologies were proposed in this paper, which is summarized as 'One objective, Three analyses, Five definitudes and Seven improvements'.

Identification of major components of traditional Chinese medicine Naodesheng tablet by HPLC-DAD-MS(n) / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To identify the major components of traditional Chinese medicine Naodesheng tablet.</p><p><b>METHODS</b>A HPLC-DAD-MS(n) based method was developed to analyze and identify the major components of Naodesheng tablet. Separation was performed on an Agilent Zorbax SB-C(18) column (4.6 mm X 250 mm, i.d, 5 μm) with mobile phase consisting of water with 0.05 % formic acid and acetonitrile as gradient eluent at the flow rate of 0.5 ml.min(-1).</p><p><b>RESULTS</b>A total of 43 components were detected, among which 22 were identified by comparing their UV absorption profiles, the information of molecular Glucosyl puerarin weights, and structures provided by ESI-MS(n) with those of available standards and reference data, such as Safflor yellow A, 4'-O-Glucosyl puerarin, 3'-hydroxypuerarin, Genistein-8-C-apiosyl (1-6) glucoside, Puerarin, 6"-O-xylosyl puerarin, 6"-O-apiosyl puerarin, 3'-methoxy puerarin, 3'-methoxy-6"-o-xylosyl puerarin, Daidzin, Genistin, Pueroside A, Notoginsenoside R(1), Ginsenoside Re, Ginsenoside Rg1,Daidzein,Biochanin A,Ginsenoside Rb(1), Ginsenoside Rc, Ginsenoside Rb(2), Ginsenoside Rb(3), Ginsenoside Rd.</p><p><b>CONCLUSION</b>The proposed method can identify the main components of Naodesheng tablet and provide information for the quality control of this medicine.</p>

A method for predicting activity of traditional Chinese medicine based on quantitative composition-activity relationship of neural network model / 中国中药杂志

<p><b>OBJECTIVE</b>To study a method for evaluating the quality of traditional Chinese medicine (TCM) according as their activity.</p><p><b>METHOD</b>Combined with partial least squares (PLS), BP and RBF neural networks were selected to establish the model of quantitative composition-activity relationship (QCAR) due to their strong approximation capabilities for nonlinear function respectively. The activity of TCM was predicted with the QCAR model, and the quality of TCM was evaluated according to the predicted activity.</p><p><b>RESULT & CONCLUSION</b>The proposed method was applied to evaluate the quality of Chuanxiong. The results indicated that, in the indexes including training error, prediction error and correlation coefficient, the established model is better than the model established by principal component regression or PIS regression. The new model can accurately represent the complicated nonlinear relationship between the components and the bioactivity of Chuanxiong. Consequently, this method has potential to evaluate the quality of TCM according to bioactivity.</p>