"Component-target-efficacy" network analysis and experimental verification of Qingkailing Oral Preparation / 中国中药杂志

This study aims to explore the mechanism of Qingkailing(QKL) Oral Preparation's heat-clearing, detoxifying, mind-tranquilizing effects based on "component-target-efficacy" network. To be specific, the potential targets of the 23 major components in QKL Oral Preparation were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The target genes were obtained based on UniProt. OmicsBean and STRING 10 were used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. Cytoscape 3.8.2 was employed for visualization and construction of "component-target-pathway-pharmacological effect-efficacy" network, followed by molecular docking between the 23 main active components and 15 key targets. Finally, the lipopolysaccharide(LPS)-induced RAW264.7 cells were adopted to verify the anti-inflammatory effect of six monomer components in QKL Oral Preparation. It was found that the 23 compounds affected 33 key signaling pathways through 236 related targets, such as arachidonic acid metabolism, tumor necrosis factor α(TNF-α) signaling pathway, inflammatory mediator regulation of TRP channels, cAMP signaling pathway, cGMP-PKG signaling pathway, Th17 cell differentiation, interleukin-17(IL-17) signaling pathway, neuroactive ligand-receptor intera-ction, calcium signaling pathway, and GABAergic synapse. They were involved in the anti-inflammation, immune regulation, antipyretic effect, and anti-convulsion of the prescription. The "component-target-pathway-pharmacological effect-efficacy" network of QKL Oral Preparation was constructed. Molecular docking showed that the main active components had high binding affinity to the key targets. In vitro cell experiment indicated that the six components in the prescription(hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide) can reduce the expression of nitric oxide(NO), TNF-α, and interleukin-6(IL-6) in cell supernatant(P<0.05). Thus, the above six components may be the key pharmacodynamic substances of QKL Oral Preparation. The major components in QKL Oral Prescription, including hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide, cholic acid, isochlorogenic acid A, and γ-aminobutyric acid, may interfere with multiple biological processes related to inflammation, immune regulation, fever, and convulsion by acting on the key protein targets such as IL-6, TNF, prostaglandin-endoperoxide synthase 2(PTGS2), arachidonate 5-lipoxygenase(ALOX5), vascular cell adhesion molecule 1(VCAM1), nitric oxide synthase 2(NOS2), prostaglandin E2 receptor EP2 subtype(PTGER2), gamma-aminobutyric acid receptor subunit alpha(GABRA), gamma-aminobutyric acid type B receptor subunit 1(GABBR1), and 4-aminobutyrate aminotransferase(ABAT). This study reveals the effective components and mechanism of QKL Oral Prescription.

Identification of Q-markers for Cistanches Herba based on HPLC-Q-TOF-MS/MS and network pharmacology / 中国中药杂志

This study aims to establish a method for analyzing the chemical constituents in Cistanches Herba by high performance liquid chromatography(HPLC) and quadrupole-time-of-flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS), and to reveal the pharmacological mechanism based on network pharmacology for mining the quality markers(Q-markers) of Cistanches Herba. The chemical constituents of Cistanche deserticola and C. tubulosa were analyzed via HPLC-Q-TOF-MS/MS. The potential targets and pathways of Cistanches Herba were predicted via SwissTargetPrediction and DAVID. The compound-target-pathway-pharmacological action-efficacy network was constructed via Cytoscape. A total of 47 chemical constituents were identified, involving 95 targets and 56 signaling pathways. We preliminarily elucidated the pharmacological mechanisms of echinacoside, acteoside, isoacteoside, cistanoside F, 2'-acetylacteoside, cistanoside A, campneoside Ⅱ, salidroside, tubuloside B, 6-deoxycatalpol, 8-epi-loganic acid, ajugol, bartsioside, geniposidic acid, and pinoresinol 4-O-β-D-glucopyranoside, and predicted them to be the Q-markers of Cistanches Herba. This study identified the chemical constituents of Cistanches Herba, explained the pharmacological mechanism of the traditional efficacy of Cistanches Herba based on network pharmacology, and introduced the core concept of Q-markers to improve the quality evaluation of Cistanches Herba.

Analysis and prediction of quality markers of Lonicerae Japonicae Flos / 中国中药杂志

Lonicerae Japonicae Flos, as common Chinese medicine, has been used for thousands of years in the treatment of inflammation and infectious diseases with definite efficacies. The complex composition of Lonicerae Japonicae Flos results in its extensive pharmacological effects, so the assessment of its quality by only a few index components is not comprehensive. Guided by the quality marker(Q-marker), the present study comprehensively analyzed and predicted the quality connotation of Lonicerae Japonicae Flos based on the chemical composition and component transfer, the phylogenetic relationship, chemical composition effectiveness, measurability, and specificity. Chlorogenic acid, isochlorogenic acids A, B, and C, luteoloside, rutin, sweroside, and secoxyloganin were predicted as candidate Q-markers of Lonicerae Japonicae Flos.

Study on critical quality attributes of Qingjin Huatan Decoction based on serum pharmacochemistry / 中国中药杂志

Qingjin Huatan Decoction is a classic prescription with the effects of clearing heat, moistening lung, resolving phlegm, and relieving cough. In order to explore the critical quality attributes of Qingjin Huatan Decoction, we identified the blood components of Qingjin Huatan Decoction by ultra-performance liquid chromatography quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS) under the following conditions, chromatographic column: Acquity UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm); mobile phase: 0.1% formic acid acetonitrile(A)-0.1% formic acid in water(B); gradient elution; flow rate: 0.2 mL·min~(-1); column temperature: 30 ℃; injection volume: 5 μL. The electrospray ionization(ESI) source was used to collect data in both positive and negative ion modes under the following conditions, capillary voltage: 3 kV for the positive ion mode and 2 kV for the negative ion mode; ion source temperature: 110 ℃; cone voltage: 30 V; cone gas flow rate: 50 L·h~(-1); nitrogen degassing temperature: 350 ℃; degassing volume flow rate: 800 L·h~(-1); scanning range: m/z 50-2 000. In this experiment, a total of 66 related components of Qingjin Huatan Decoction were identified, including 22 prototype components and 44 metabolites. The results of this study preliminarily revealed the pharmacodynamic material basis of Qingjin Huatan Decoction in vivo, which has provided an experimental basis for the determination of quality markers of Qingjin Huatan Decoction and the development of new drugs.

Modern research progress of traditional Chinese medicine Paeoniae Radix Alba and prediction of its Q-markers / 中国中药杂志

Paeoniae Radix Alba is the dried root of Paeonia lactiflora, which was first recorded in the Shennong's Classic of Materia Medica and listed as the top grade. It is a common blood-tonifying herb, and its chemical components are mainly monoterpenes and their glycosides, triterpenes, flavonoids and so on. Modern research has demonstrated that Paeoniae Radix Alba has the activities of anti-inflammation, pain easing, liver protection, and anti-oxidation, and thus it is widely used in clinical practice and has broad development prospects. In this paper, the research progress on the chemical composition, pharmacological effects, and quality control of Paeoniae Radix Alba were summarized. On this basis, the Q-markers of Paeoniae Radix Alba were predicted from the aspects of mass transfer and traceability, chemical composition specificity, and availability and measurability of chemical components, which will provide a scientific basis for the quality evaluation of Paeoniae Radix Alba.

Basic study on treatment of COVID-19 with Shufeng Jiedu Capsule and research and development ideas of new Chinese materia medica against COVID-19 / 中草药

Coronavirus disease 2019 (COVID-19) has become a major global epidemic, and traditional Chinese medicine (TCM) has played an important role in the prevention and control of major epidemics. Taking Shufeng Jiedu Capsule as an example, this paper summarized the ideas and research practice of TCM in early intervention, blocking disease progression, improving symptoms, anti-inflammation and immunoregulation, suppressing "cytokine storm", syndrome differentiation and playing the advantages of compatibility based on the understanding of COVID-19. The idea of establishing a scientific model for the research and development of new drugs of TCM was put forward.

Research Strategies for Quality Standards of Famous Classical Formula Based on Standard Decoction (Material Reference) / 中国实验方剂学杂志

The inheritance of traditional clinical value of famous classical formulae is an important direction for the development of traditional Chinese medicine industry.Compared with the previous research and development of new drugs, the management requirement of " material reference" was introduced into the famous classical formulae research, which is used as the reference of process optimization and quality control.The characteristics of compound preparation of famous classical formulae are also reflected in the core concept of " quality inheritance of classics" in the road of industrial development.How to implement the above requirements and concepts into product development and industrial production? There are many specific common problems to be solved in practical research.How to effectively establish the " material reference" of famous classical formulae of different dosage forms? How to use " material reference" to guide the process optimization of compound preparation of famous classical formulae? How to determine the daily dose of famous classical formulae? How to take effective measures in the selection of raw material to reduce quality fluctuation range? This paper discusses the key issues such as production process and quality evaluation from the following aspects.Firstly, the management regulations and research and development guidelines are analyzed, and the specific implementation methods are given.Then, the possible problems in the Requirements for Declaration Documents (Draft for Opinions) are pointed out, and relevant suggestions are given.Finally, based on the research experience of standard decoction and famous classical formulae in the laboratory, an example is given to provide reference for the development of compound preparation of famous classical formulae.

Systematic research of secondary development of Shufeng Jiedu Capsule / 中草药

The study of secondary development of major Chinese materia medica varieties is the important content of Chinese materia medica (CMM) innovation research, and it is also the important approach of inheriting and developing traditional Chinese medine (TCM) theory and breaking the bottleneck restricting of the development of TCM theory and CMM industry. In this paper, the secondary development of Shufeng Jiedu Capsule (SJC) was systematically studied. The chemical components of SJC were elucidated by the identification and characterization of herbs, SJC and components ingested into the blood. The main effective components were further screened and cleared by integrating UPLC-Q/TOF-MS, NF-κB double luciferase reporter gene system, binding experiments of G protein coupled receptors, network pharmacology analysis, and spectrum-efficiency screening method. Based on the traditional efficacy, the mechanism of SJC was explained in terms of anti-inflammatory immunity, antipyretic effect, pharmacokinetics and tissue distribution of the main components based on the methods of animal model and genomics. The formula features, compatibility regularity were clarified and the action properties, comparative advantages and core clinical value were found and refined by the research of decomposed recipes and the comparison with the similar CMM recipes and chemical drugs. The quality control systems of SJC and related herbs were established by content determination of multi-target ingredients and multi-batch samples, and the establishment of the characteristic mode of HPLC fingerprint. The original quality standards were promoted comprehensively to ensure the uniformity, stability and controllability of product quality. This study not only provided important theoretical and experimental basis for clinical application and guidance of clinical practice, but also provided research ideas and modes for the secondary development of other major CMM varieties.

Study on quality marker of Haima Bushen Pills / 中草药

Haima Bushen Pills (HBP) is a kind of major Chinese materia medica varieties, which has been proven to be effective. However, due to its weak research foundation and simple quality control method, the quality of HBP cannot be evaluated scientifically and controlled effectively. In this paper, the chemical components of HBP and components ingested into the blood were identified and characterized based on the concept and determination principle of quality marker (Q-marker). Then, through the animal models, proteomics, metabolomics, network pharmacology, receptor binding and enzyme detection and other methods, its effectiveness was evaluated, the mechanism was explained, the effective components were determined, and the Q-marker was extracted. This paper provides theoretical and experimental evidence for giving full play to the clinical value and establishing a scientific quality evaluation system of HBP.

The concept, core theory and research methods of Chinesemedicine quality markers / 药学学报

Q-marker is a new concept of quality control for traditional Chinese medicine. Since its introduction in 2016, it has received extensive support and participation from researchers and manufactures of the entire industry. In order to establishing the research level of quality markers, normative research model, we review the proposed core theory and research methods of Chinese medicine quality markers. The definition and scientific connotation of Chinese medicine quality markers are analyzed. The core theories and research methods of quality markers are summarized from five aspects: "effectiveness", "specificity", "transfer and traceability", "compatibility environment" and "measurability" of quality markers. This paper aims to provide useful theoretical and methodological guidance for studying Chinese medicine quality markers.

A hypothesis on the Q-markers based on characteristics of opposite-effect of herbs: an example of Sanqi / 药学学报

The quality definition of traditional Chinese medicine (TCM) is a hot area in modern research of TCM. In recent years, the characteristics of one herb with multiple effects have been widely accepted and studied. The typical opposite-effect of herbs is considered as a special part of one herb with multiple effects, and was summarized in this paper. Sanqi was used as an example of opposite-effect herbs for developing the strategies and approaches on the Q-markers. The traditional opposite-effect should be studied by modern pharmacological research methods. The correlation of the chemical components with the opposite effects should be established in order to verify the material basis and evaluate the mechanism including targets and pathways. The unique characteristics of chemical components should be analyzed and defined. Finally, the Q-markers of the opposite effect herb will be confirmed. This paper provides a useful reference for the precise quality control of herbal opposite-effects.

A smart near-infrared spectroscopy evaluation system for quality management of Chinese medicinal materials based on quality markers / 药学学报

The quality of traditional Chinese medicine (TCM) is the lifeline for TCM industry. The development of artificial intelligence (AI) has provided new means for the quality management of Chinese medicinal materials (CMM). In this paper, we take the quality marker (Q-marker) as a breakthrough point, focused on the research strategy from chemical markers to Q-markers, picked up the characteristics of the Q-markers from the near infrared spectrum (NIRS), and explored the feasibility of establishing the NIRS assay based on Q-marker. After integrated the biological activity detection and artificial neural network algorithm, we try to establish the relationship between the spectral properties of NIRS and specific efficacy of the CMM. Finally, the bottlenecks will be solved that related to the transmission and traceability of quality attributes in the process of TCM production, quantity change, overall quality management and so on. This system is going to improve TCM quantity scientific and intelligent supervision, and promote the upgrading of traditional TCM industry.

Research approaches of quality marker (Q-marker) of Chinese materia medica formula based on “five principles” / 中草药

Q-marker of Chinese materia medica (CMM) is a latest proposed core concept of CMM quality evaluation and quality control. A wide range of relevant researches on the Q-marker have been carried out by science and technology workers since the concept was put forward. However, to date, most studies are still limited to Q-marker studies of single herbs and pieces and cannot fully reflect all the elements of the concept of Q-marker. In this paper, the scientific connotation of five elements and the principles, ideas and approaches for the discovery and determination of CMM Q-marker were systemically discussed from the perspectives of quality transmissibility and traceability, ingredient specificity, component validity, component measurability, and formula compatibility environment. Moreover, research approaches of Q-marker of CMM formula based on “five principles” were proposed. The examples of representative researches provide a systematic research idea and reference for the research and discovery of CMM Q-marker.

Method of quality marker research and quality evaluation of Chinese materia medica based on drug properties and effect characteristics / 中草药

The quality of Chinese materia medica (CMM) is the lifeline of Chinese medicine industry. However, many problems are still found in the quality study on CMM, which restricts the healthy development of Chinese medicine industry to a certain extent. Aiming at the problems existing in the quality research on CMM, the research idea, method and approach of quality marker research and quality evaluation of CMM were put forward based on systematic analysis and discussion on the basic properties and clinical features of CMM according to the core concept of quality marker and the combination of research practice, from the perspective of transmission and traceability of quality elements, the relationship between chemical composition and traditional efficacy containing "drug property" and "drug function", composition analysis of endemicity based on pharmacophylogenetic study and biosynthetic approach. Finally, a new integrated mode of CMM quality evaluation and control was established.

Study of secondary development of Liujing Toutong Tablets / 中草药

To study the secondary development of major Chinese materia medica (CMM) varieties is the important content of CMM innovation research, and it is also the important approach of inheriting and developing traditional Chinese medicine (TCM) theory and breaking the bottleneck restricting the development of TCM theory and CMM industry development. In this paper, the secondary development of Liujing Toutong Tablets (LTT) was systematically studied. The chemical components of LTT were elucidated by identification and characterization of herbs, LTT and components ingested into the blood. The main effective components were further screened and cleared by binding experiments of G protein coupled receptors and network pharmacology analysis. The mechanism of LTT was explained by the studies of animal models, isolated organs, cells, functional receptors, and network pharmacology related with headache. The formula features, compatibility regularity were clarified and the action properties, comparative advantages and core clinical value were found and refined by the research of decomposed recipes and the comparison with the similar CMM recipes and chemical drugs. The quality control systems of LTT and related herbs were established by systematic research of identification and characterization of chemical components, the LTT chemical information herbal source, content determination of multi-target ingredients, establishment of the characteristic mode of HPLC fingerprint, sample determination of multiple batches. The original quality standards were promoted comprehensively ensuring the uniformity, stability and controllability of product quality. This study not only provided important theoretical and experimental basis for clinical application and guiding clinical practice, but also provided research ideas and modes for the secondary development of other major CMM.

Research strategies in standard decoction of medicinal slices / 中国中药杂志

This paper discusses the research situation of the standard decoction of medicinal slices at home and abroad. Combined with the experimental data, the author proposes that the standard decoction of medicinal slices is made of single herb using standard process which should be guided by the theory of traditional Chinese medicine, based on clinical practice and referred to modern extraction method with a standard process. And the author also proposes the principles of establishing the specification of process parameters and quality standards and established the basis of drug efficacy material and biological reference. As a standard material and standard system, the standard decoction of medicinal slices can provide standards for clinical medication, standardize the use of the new type of medicinal slices especially for dispensing granules, which were widely used in clinical. It can ensure the accuracy of drugs and consistency of dose, and to solve current supervision difficulties. Moreover the study of standard decoction of medicinal slices will provide the research on dispensing granules, traditional Chinese medicine prescription standard decoction and couplet medicines standard decoction a useful reference.

Quality markers research on Chinese materia medica: Quality evaluation and quality standards of Corydalis Rhizoma / 中草药

Corydalis Rhizoma was taken as an example for demonstration research based on the concept of quality markers (Q-markers), confirmed standards and research modes were proposed by the author. The chemical constituents of Corydalis Rhizoma were identified using high performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (HPLC/ESI-Q-TOF MS). The source and specificity of chemical constituents were confirmed by analyzing biosynthetic pathway and component specificity. The major effective components were clarified through efficacy, drug property, pharmacokinetic studies, and correlation analysis of chemical constituents. The Q-markers were determined by integrating all the results of the studies. At last, seven alkaloidal compounds including tetrahydropalmatine, corydaline, coptisine, palmatine, dehydrocorydaline, tetrahydrojatrorrhizine, and protopine have been selected as Q-markers and quality control methods of multi-component assaying and fingerprint have been established.

Promotion on systematic quality standard of Shufeng Jiedu Capsule / 中草药

The idea and model of quality research on traditional Chinese medicinal materials and compound Chinese materia medica were established and this method was applied to systematical promoting the quality standard of raw herbal materials and preparation of Shufeng Jiedu Capsule (SJC). The chemical components from Polygoni Cuspidati Rhizoma et Radix, Forsythiae Fructus, Isatidis Radix, Bupleuri Radix, Patriniae cum Radice Herba, Verbenae Herba, Phragmitis Rhizoma, and Glycyrrhizae Radix et Rhizoma were identified and 184 compounds were determined. The fingerprints of the eight medicinal materials were established, 10 compounds were identified as the anti-inflammatory substance of SJC by studying the correlation between chemical components and their anti-inflammation effect. The methods of multi-component determination and fingerprint controlling have been established and the quality standard of SJC has been improved comprehensively.

Relation of "property-response-component" and action mechanism of Yuanhu Zhitong Dropping Pills based on quality marker (Q-Marker) / 中草药

The research of effective components of Chinese materia medica (CMM) is one of the key points of modernization of traditional Chinese medicine (TCM), is the core of interpreting overall efficacy and mechanism of TCM, and is the important foundation of realizing the safety, efficacy, and quality control of CMM. Previous studies mostly focused on the binary research mode of "component-effect". However, in this paper, the triarchic theory of "property-effect-component" was proposed and the research strategy and mode of exploring the mechanism, effective components, and quality markers (Q-Marker) of TCM were established based on the basic properties of TCM, basic concepts and terms of TCM theory and also related with the core contents of TCM theory including syndrome differentiation and treatment, rules of treatment, method of treatment, compatibility regularity, and drug property. The Yuanhu Zhitong Dropping Pills (YZDP) were taken as an example for demonstration research and corydaline, tetrahydropalmatine, protopine, imperatorin, and isoimperatorin were determined to be the Q-Marker of YZDP.

Historical story on natural medicinal chemistry: Artemisinin-a milestone of traditional Chinese medicine study / 中草药

2015 Nobel Prize was awarded to Professor TU You-you, which fill the gap of Chinese scientists in the Nobel Prize in natural science. The discovery of artemisinin is a brilliant record in the history of science in the world. This is also a great inspiration for scientific community, especially for natural medicine researchers. This paper summarized the historical evolution of artemisinin, expressing the respects to the last generation of scientists and encouraging the younger researchers in this field. This article is one of the series of historical stories on natural product chemistry written by the authors.