Clinical Application and Quality Analysis of Classical Formula Xiaoyaowan： A Review / 中国实验方剂学杂志

Xiaoyaowan has the effects of soothing the liver， invigorating the spleen， regulating menstruation， and nourishing blood. It is often used to treat the distending pain of the chest and hypochondriac， loss of appetite， dizziness， and irregular menstruation caused by liver depression and spleen deficiency. The formula originated from the Sinisan of Treatise on Cold Damage（《伤寒论》） in the Han dynasty and was officially formulated in the Song dynasty's Taiping Royal Prescriptions（《太平惠民合计局方》）. In the Ming and Qing dynasties， it was developed into more comprehensive formulas such as modified Bazhentang， modified Xiaoyaowan， and other formulas. In recent years， Xiaoyaowan has become a classic formula for treating many symptoms of liver depression. The Pharmacopoeia of the People's Republic of China（《中华人民共和国药典》）， 2020 edition， records Xiaoyaowan and modified Xiaoyaowan. Modern clinical research has further expanded the therapeutic range of this formula. Through literature research， it is found that there are certain reports on the clinical application and quality analysis of Xiaoyaowan， but the relevant literature lacks collation so far. Therefore， relevant literature was consulted and sorted out. The paper summarized the treatment of mammary hyperplasia， depression， irregular menstruation， melasma， menopausal syndrome， and polycystic ovary syndrome with Xiaoyaowan， as well as the quality analysis of paeoniflorin， ferulic acid， and glycyrrhizinic acid of Xiaoyaowan. It is expected to lay a foundation for further research on clinical application， pharmacodynamic mechanism， and quality control of this classic formula.

Research on Preparation Process and Quality Evaluation of Traditional Chinese Medicine Dispensing Granules and Its Consistency with Traditional Decoction： A Review / 中国实验方剂学杂志

Traditional Chinese medicine dispensing granules（TCMDGs）is the new type of decoction pieces with the development of modernization of TCM， which has received mixed opinions since its practical application. In 2021， the national departments issued Announcement on Ending the Pilot Work of TCMDGs， marking the end of the 28-year pilot work of TCMDGs， and eligible TCM enterprises can produce TCMDGs after filing. However， this does not mean that the preparation process， quality standard and efficacy research of TCMDGs have been developed and matured， on the contrary， there are still some problems that need to be solved and gradually improved. For example， in the production process， there are problems such as unclear， unified and non-standardized preparation parameters. In terms of quality control， there are some problems such as lack of producing area regulation， variety selection and processing specification. In terms of consistency evaluation with traditional decoction， there are problems such as unclear relationship between the chemical constituents and pharmacological effects of the two. Therefore， in view of some prominent problems of TCMDGs at present， this paper takes the published literature as the main data source and combines the specific requirements of the code or technical standards such as the 2020 edition of Chinese Pharmacopoeia， Publicity of the Unified Standard on the Varieties of TCMDGs， Quality Control and Standard Formulation Technical Requirements of TCMDGs. The production process of TCMDGs， the origin and variety of raw materials， the processing of decoction pieces， the quality control standard and the consistency evaluation of formula granules and traditional decoction were sorted out and visualized by literature mining， data analysis and list comparison. Based on the analysis results， the following suggestions were made. In terms of preparation process， the completeness and standardization of process parameters should be strengthened. In terms of quality evaluation， attention should be paid to the relationship between the authenticity， variety， processing and quality of medicinal materials. In the consistency evaluation of formula granules and traditional decoction， the deep difference and mechanism between TCMDGs and traditional decoction were discussed by combining structural Chinese medicine， quality marker（Q-Marker） theory and physicochemical characterization， so as to provide reference for the application and development of TCMDGs.

Predictive Analysis of Quality Markers of Anticoagulant Activity of Kunning Granules Based on UHPLC-Q-TOF-MS/MS and Spectral Efficacy / 中国实验方剂学杂志

ObjectiveTo perform a predictive analysis of the quality marker（Q-Marker） for the anticoagulant activity of Kunning granules. MethodThe chemical components of Kunning granules were analyzed by ultra high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry（UHPLC-Q-TOF-MS/MS） on a Waters ACQUITY UPLC HSS T3 column（2.1 mm×100 mm， 1.8 μm） with the mobile phase of acetonitrile（A）-25 mmol∙L-1 ammonium acetate aqueous solution（B） for gradient elution （0-5 min， 5%-22%A； 5-10 min， 22%-30%A； 10-15 min， 30%-95%A； 15-20 min， 95%-5%A； 20-30 min， 5%A）， flow rate of 0.2 mL∙min-1， column temperature at 30 ℃， injection volume of 1 μL， electrospray ionization（ESI）， positive and negative ion detection modes. Interaction analysis between the targets of chemical components and the targets of abnormal uterine bleeding（AUB） was performed by network pharmacology， and the key components were screened through network topology analysis. The fingerprints of 10 batches of Kunning granules were established by high performance liquid chromatography（HPLC）， the anticoagulant activity of the granules was determined by blood coagulation method and fibrinogen plate method， and the spectrum-effective relationship was established. The components co-occurring in the topological analysis and spectrum-effective relationship were selected as Q-Markers， and their anticoagulant activities were verified and confirmed. ResultA total of 475 chemical components were identified from Kunning Granule， of which 22 key components such as salvianolic acid B， paeoniflorin， naringin and neohesperidin， were the potential material basis for the treatment of AUB. The spectrum-effective analysis showed that peaks 7（paeoniflorin）， 9（naringin）， 10（neohesperidin） and 11（salvianolic acid B） were the optimal principal components， and in vitro activity test showed that these four components could better characterize their anticoagulant activity. ConclusionSalvianolic acid B， paeoniflorin， neohesperidin and naringin may be Q-Markers for the anticoagulant activity of Kunning granules.

Multimodal integrated strategy for the discovery and identification of quality markers in traditional Chinese medicine / 药物分析学报

With the modernization and internationalization of traditional Chinese medicine(TCM),the requirement for quality control has increased.The quality marker(Q-marker)is an important standard in this field and has been implemented with remarkable success in recent years.However,the establishment of Q-markers remains fragmented and the process lacks systematicity,resulting in inconsistent quality control and insufficient correlation with clinical efficacy and safety of TCM.This review introduces four multi-modal integrated approaches that contribute to the discovery of more comprehensive and accurate Q-markers,thus aiding in the establishment of new quality control patterns based on the characteristics and principles of TCM.These include the whole-process quality control strategy,chemical-activity-based screening method,efficacy,safety,and consistent combination strategy,and TCM theory-guided approach.Furthermore,methodologies and representative examples of these strategies are described,and important future directions and questions in this field are also proposed.

Q-marker prediction analysis of Gentiana rigescens Franch. based on HPLC and network pharmacology / 药学学报

Aa a characteristic medicinal plant in China, Gentiana rigescens Franch. has the function of protecting the liver and invigorating the spleen. At present, there are a few studies on the content determination method of characteristic components of G. rigescens, so it is necessary to establish a scientific and effective quality control method; In this study, The high performance liquid chromatography (HPLC) fingerprint of G. rigescens was established, based on literature reviewed and characteristic spectrum identified, the source range of G. rigescens quality marker (Q-marker) was screened. The effectiveness of the ingredients and the corresponding targets and pathways was analyzed through network pharmacology, and drew the diagram of ''component-target-pathway''. Qualitative and quantitative analysis of G. rigescens was performed by HPLC, and screen the main marker components leading to the differences between groups which were determined the Q-marker of G. rigescens; The literature and HPLC had determined that five iridoids were the main source of G. rigescens Q-marker. The network pharmacology (effectiveness) and qualitative and quantitative (detectability) analysis of G. rigescens from different producing areas confirmed that gentiopicroside, swertiamarin, and sweroside can be used as the main landmark components, and there were significant differences in their contents among different producing areas; The analysis of G. rigescens from different producing areas was carried out by network pharmacology and chemical fingerprints, it is confirmed can be used as potential Q-marker to provide sufficient theoretical basis for the quality control of G. rigescens in the later period.

Present Situation Analysis and Thinking on Quality Control Mode of Chinese Materia Medica / 中国实验方剂学杂志

The quality of Chinese materia medica is the premise to ensure its safety and effectiveness in clinical application， and the standardization of Chinese materia medica quality is the most important to realize the sustainable development of traditional Chinese medicine （TCM）. At present， the quality control system of Chinese materia medica has been transformed from a single chemical evaluation to the overall quality control guided by clinical efficacy. However， some quality control items of decoction pieces are still lacking or imperfect in the drug standard of prescription， which makes it difficult to guarantee the effectiveness and safety of Chinese materia medica in clinical application. Based on this， the quality control models and innovative ideas of Chinese materia medica were analyzed and discussed from the perspectives of chemical analysis， biological evaluation and clinical application in this paper. Aiming at the existing problems and actual needs in the control system of Chinese materia medica， this paper proposed the improvement strategies in accordance with the characteristics of TCM， in order to provide theoretical basis for the related research on quality control of Chinese materia medica.

Present Situation Analysis and Thinking on Quality Control Mode of Chinese Materia Medica / 中国实验方剂学杂志

The quality of Chinese materia medica is the premise to ensure its safety and effectiveness in clinical application， and the standardization of Chinese materia medica quality is the most important to realize the sustainable development of traditional Chinese medicine （TCM）. At present， the quality control system of Chinese materia medica has been transformed from a single chemical evaluation to the overall quality control guided by clinical efficacy. However， some quality control items of decoction pieces are still lacking or imperfect in the drug standard of prescription， which makes it difficult to guarantee the effectiveness and safety of Chinese materia medica in clinical application. Based on this， the quality control models and innovative ideas of Chinese materia medica were analyzed and discussed from the perspectives of chemical analysis， biological evaluation and clinical application in this paper. Aiming at the existing problems and actual needs in the control system of Chinese materia medica， this paper proposed the improvement strategies in accordance with the characteristics of TCM， in order to provide theoretical basis for the related research on quality control of Chinese materia medica.

Research on Q-markers of Polygoni Perfoliati Herba based on analytic hierarchy process-entropy weight method and fingerprints / 中国中药杂志

The potential quality markers(Q-markers) of Polygoni Perfoliati Herba were studied based on analytic hierarchy process(AHP)-entropy weight method(EWM), network pharmacology, and spectrum-effect relationship analysis. The AHP-EWM was used for quantitative identification of the Q-markers. To be specific, AHP was applied for the weight analysis of the validity, testability, and specificity of the first-level indexes, and EWM for the analysis of the second-level indexes supported by literature and experimental data. Based on literature and network pharmacology, the validity analysis was to study the component-target-disease-efficacy network, and select the components with the strongest correlation with the efficacy of clearing heat and removing toxin, diuresis and alleviating edema, and relieving cough. For the testability analysis, the high performance liquid chromatography(HPLC) and literature research were used to determine the 10 components in Polygoni Perfoliati Herba, and the fingerprints of Polygoni Perfoliati Herba were established at the same time. The specificity analysis was based on the statistics of the number of plants in which the components existed. Thereby, the 11 compounds: quercetin, oleanolic acid, ellagic acid, gallic acid, kaempferol, rutin, esculetin, quercetin-3-O-glucuronide, ursolic acid, protocatechuic acid, and ferulic acid, were identified as potential Q-markers. The 11 compounds were identified to have high anti-inflammatory activity, indicating that the 11 Q-markers may be the functional material basis. The result in this study is expected to serve as a reference for the quality control of Polygoni Perfoliati 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.

Prediction of Q-markers of Astragali Radix based on network pharmacology and fingerprint / 中国中药杂志

Astragali Radix is one of the most commonly used medicinal materials. In recent years, its cultivated varieties and a variety of adulterants have flooded the market, which makes its quality uneven, and the development of quality control methods has become a research hotspot. Therefore, figuring out the quality markers of Astragali Radix is of great significance for its comprehensive evaluation. In this study, the fingerprints of 15 batches of Astragali Radix were established by HPLC, and the main components causing intergroup differences were screened out by PLS-DA. On the basis of literature review and network pharmacology analysis, the targets and pathways of active ingredients were obtained from SwissTargetPrediction, PubChem Compound and other databases, and then the "component-target-pathway" network was constructed with Cytoscape 3.7.1 for the prediction of potential quality markers. Twenty-eight common peaks were identified in the established fingerprint, and three differential components were selected as potential quality markers for Astragali Radix, which were astragaloside Ⅳ, calycosin-7-O-β-D-glucoside and ononin. The proposed method based on HPLC fingerprint of Astragali Radix is convenient and feasible, facilitating the improvement in its quality control.

Q-marker prediction of Magnoliae Officinalis Cortex before and after "sweating" / 中国中药杂志

Magnoliae Officinalis Cortex, a common Chinese medicinal in clinic, should undergo "sweating" process in producing area according to Chinese Pharmacopoeia, which affects its genuineness and quality. In light of the concept and research mode of quality marker(Q-marker) for decoction pieces, the active components of Magnoliae Officinalis Cortex pieces which altered significantly before and after "sweating" were identified in this study. The main pharmacodynamic material basis was clarified by pharmacodynamic, pharmacokinetic and drug property research, followed by the prediction of Q-markers of Magnoliae Officinalis Cortex before and after "sweating", for better improving its quality standard.

Research progress on chemical constituents and pharmacological effects of Glycyrrhizae Radix et Rhizoma and discussion of Q-markers / 中国中药杂志

Glycyrrhizae Radix et Rhizoma, a traditional Chinese herbal medicine, mainly contains triterpenoids, flavonoids, polysaccharides, coumarins and volatile oils with many pharmacological activities such as anti-tumor, anti-bacterial, anti-viral, anti-inflammatory, immune regulatory and anti-fibrotic effects. The widespread applications of Glycyrrhizae Radix et Rhizoma in food, medicine and chemical industries make its demand increase gradually. Therefore, the quality guarantee of the medicinal is of great value. Starting from the elaboration of chemical components and pharmacological effects of Glycyrrhizae Radix et Rhizoma and the introduction to the concept of quality marker(Q-marker), this study analyzed the Q-markers of Glycyrrhizae Radix et Rhizoma from the aspects of plant phylogene-tics, chemical component specificity, traditional efficacy, traditional medicinal properties, absorbed components, different processing methods and so on, which provides reference for quality evaluation, development and utilization of Glycyrrhizae Radix et Rhizoma.

Research on Q-markers of Eupatorium lindleyanum based on analytic hierarchy process-entropy weight method and network pharmacology / 中国中药杂志

The potential quality markers( Q-markers) of Eupatorium lindleyanum were studied with analytic hierarchy process(AHP)-entropy weight method(EWM) and network pharmacological method. Based on the concept of Q-markers of traditional Chinese medicine, AHP-EWM was employed to quantitatively identify the Q-markers of E. lindleyanum. AHP method was applied to the weight analysis of the validity, testability, and specificity of the first-level indexes, and EWM method was used to analyze the secondlevel indexes supported by literature and experimental data. At the same time, based on the theory and method of network pharmacology, the component-target-disease-efficacy network of E. lindleyanum was built, and the components most closely related to the efficacy of resolving phlegm and relieving cough and asthma were screened out. Through the integrated analysis of the results obtained with AHP-EWM and network pharmacological method, 13 compounds including rutin, quercetin, nepetin, cirsiliol, luteolin, hyperoside,isoquercitrin, kaempferol, caffeic acid, eupalinolide K, eupalinolide A, eupalinolide B, and eupalinolide C were comprehensively identified as the potential Q-markers of E. lindleyanum. The results provide a basis for the quality control of E. lindleyanum.

Research progress of Phyllanthi Fructus and prediction of its Q-markers / 中国中药杂志

Phyllanthi Fructus, a unique Chinese and Tibetan medicinal plant with both edible and medical values, has high potential of cultivation and development. The resources of Phyllanthi Fructus in China are rich, mainly distributed in Yunnan, Sichuan, Fujian, Guangdong, Guangxi, etc. Phyllanthi Fructus is widely used in the clinical practice of Chinese medicine and plays an important role in Tibetan medicine, Uyghur medicine, Yi medicine, and Mongolian medicine. Phyllanthi Fructus mainly contains phenolic acids,tannins, terpenes, sterols, fatty acids, flavonoids, amino acids and other compounds. Modern pharmacological studies show that Phyllanthi Fructus has antioxidant, anticancer, blood lipid-lowering, liver protective, antimicrobial, anti-inflammatory, and immune regulatory activities. In this paper, the research status of Phyllanthi Fructus was reviewed from the aspects of herbal textual research,chemical composition, and pharmacological action. The quality markers(Q-markers) of Phyllanthi Fructus were predicted and analyzed from the aspects of biogenic pathway, specificity and measurability of chemical components, efficacy, properties, new clinical uses, drug-food homology, and transformation of polyphenols. The results will provide a scientific basis for the quality control, quality evaluation, and standard formulation of Phyllanthi Fructus.

Research progress on chemical constituents and pharmacological activities of seabuckthorn and prediction of its Q-markers / 中国中药杂志

Seabuckthorn contains flavonoids, tannins, terpenoids, polysaccharides, and vitamins, which have anti-inflammation,anti-oxidation, liver protection, anti-cardiovascular disease, anti-aging, immune enhancing, anti-tumor, and anti-bacterial activities.We reviewed the papers focusing on the chemical constituents, pharmacological activities, and utilization of seabuckthorn. The quality markers(Q-markers) of seabuckthorn were predicted and analyzed based on original plant phylogeny, chemical composition correlation, traditional medicinal properties, pharmacodynamic correlation, traditional and extended efficacy, pharmacokinetics, metabolic processes, and measurable components. With this review, we aim to provide theoretical reference for the quality control and quality standard establishment of seabuckthorn, so as to promote the rational exploitation and utilization of seabuckthorn resources, and improve the healthy and sustainable development of seabuckthorn industry.

Review of chemical composition, pharmacological effects, and clinical application of Salviae Miltiorrhizae Radix et Rhizoma and prediction of its Q-markers / 中国中药杂志

Salviae Miltiorrhizae Radix et Rhizoma is a Chinese herbal medicine that promotes blood circulation to remove blood stasis, nourishes blood to tranquilize the mind, and cools blood to disperse carbuncles. Salviae Miltiorrhizae Radix et Rhizoma has microcirculation-improving, blood vessel-dilating, atherosclerosis-preventing, anti-inflammatory, anti-tumor, and blood pressure-and blood lipid-lowering activities. As research progresses, the chemical composition, pharmacological effect, and clinical application of Salviae Miltiorrhizae Radix et Rhizoma have attracted much attention. We reviewed the research progress in this field. Based on the concept of quality marker(Q-marker) in traditional Chinese medicine, the Q-markers of Salviae Miltiorrhizae Radix et Rhizoma were predicted and analyzed from the aspects of quality transfer, traceability, ingredient specificity, association between ingredients and pharmacological effects, ingredient predictability, and compounding environment. This review provides a scientific basis for the quality control of Salviae Miltiorrhizae Radix et Rhizoma and its preparations.

Research progress in Terminalia chebula and its predictive analysis on Q-marker / 中草药

Terminalia chebula is a traditional Chinese herbal medicine, which distributed in Yunnan, Guangdong, Guangxi, Tibet and etc. T. chebula is widely used in the clinical medicine of Chinese medicine and it plays a significant role in the Mongolian medicine and the Tibetan medicine. The chemical composition of T. chebula is rich and diverse, including phenolic acids, tannins, triterpenoids, aliphatics, flavonoids, volatile oils, amino acids, trace elements, carbohydrates and so on. Modern pharmacological studies have shown that T. chebula extract has many pharmacological activities, such as anti-oxidation, anti-cancer, anti-tumor, detoxification, antibacterial, strong heart, anti-inflammation, immunomodulation, anti-microbial, and promoting bronchial smooth muscle contraction. From the aspects of textual research, chemical composition characteristics, pharmacological action and so on, this paper expounds the research progress of T. chebula. According to the core concept of Q-marker, we predicted and analyzed the quality markers of T. chebula from the aspects of chemical composition characteristics, traditional efficacy, medicinal properties, pharmacokinetics, new clinical use and measurable composition. It provides reference for the quality evaluation of T. chebula.

Chemical components and pharmacological action for Euodiae Fructus and predictive analysis on its Q-marker / 中草药

Euodiae Fructus is one of the most commonly used traditional Chinese medicinal materials with rich resource and wide distribution. It has broad prospects for development and utilization. The chemical constituents of Euodiae Fructus are abundant, including alkaloids, bitter principles, volatile oils, flavonoids and so on. Traditionally, the alkaloids and bitter principles are considered as its main pharmacodynamic components. Based on the review of its chemical composition and pharmacological action of herbal medicine, according to the theory of quality marker, the quality maker of Euodiae Fructus were predicted from the aspects of source, chemical composition and traditional efficacy, traditional medicinal properties, new clinical uses, and toxicity, measurable ingredients, blood-entering ingredients and different compatible environments, which provide a basis for defining quality markers and formulating scientific quality standards of Euodiae Fructus.

Predictive analysis of Q-marker of Glycyrrhizae Radix et Rhizoma based on network pharmacology combined with qualitative and quantitative research / 中草药

Objective: To make a preliminary prediction of the Q-marker of Glycyrrhizae Radix et Rhizoma from the perspective of the effectiveness and measurability of chemical components based on the concept of Q-marker of Chinese materia medica. Methods: Based on literature integration and data analysis, the source range of Glycyrrhizae Radix et Rhizoma Q-marker was screened, and the effectiveness of the ingredients was analyzed through network pharmacology. Qualitative and quantitative analysis of 15 batches of Glycyrrhizae Radix et Rhizoma from four places of origin was performed by HPLC. The pattern recognition method was used to screen out the main marker components that caused the differences between groups, which were combined with network pharmacological results to further determine the Q-marker of Glycyrrhizae Radix et Rhizoma. Results: Literature studies had determined that flavonoids and triterpenoids were the main source of Glycyrrhizae Radix et Rhizoma Q-marker; Network pharmacology results showed that liquiritin, glycyrrhizic acid and other components had high connectivity in the "component-target-pathway" network and were the main active components; The fingerprints of 15 batches of Glycyrrhizae Radix et Rhizoma samples were established, and five components, including liquiritin and liquiritin apioside, were identified as the main marker components by PLS-DA analysis; The content determination results of liquiritin, liquiritin apioside, glycyrrhizic acid and glycyrrhetinic acid showed that there were significant differences in the content of ingredients among different production areas. The qualitative and quantitative research on pharmacology combined with network pharmacology revealed that liquiritin, liquiritin apioside, glycyrrhizic acid and glycyrrhetinic acid can be used as Glycyrrhizae Radix et Rhizoma Q-marker. Conclusion: Taking flavonoids and triterpenoids as the source of Q-marker for Glycyrrhizae Radix et Rhizoma, the qualitative and quantitative (measurability) study of Glycyrrhizae Radix et Rhizoma herbs from multiple producing areas combined with network pharmacology (effectiveness) revealed liquiritin, liquiritin apioside, glycyrrhizic acid and glycyrrhetinic acid as the potential Q-marker of Glycyrrhizae Radix et Rhizoma are scientific and reasonable, which provide reference for quality control of Glycyrrhizae Radix et Rhizoma.

Analysis of Curcuma longa Q-markers based on traditional efficacy and modern research / 中草药

Curcuma longa, a well-known traditional Chinese medicine, which is warm in nature, acrid and bitter in taste. It has the effects of supplementing qi and activating blood circulation, treating amenorrhea, and pain relief. It was first collected in the Annotation of Materia Medica with long medication history. In this paper, chemical composition and main pharmacological activities of C. longa were summarized, and the quality markers of C. longa were predicted and analyzed based on traditional efficacy and modern research. It is suggested that the identification and quantification of ar-turmerone, α-turmerone, β-turmerone, curcumin, demethoxycurcumin, bisdemethoxycurcumin, and flavonoids should be carried out and the further research of the chemical group of terpenoids and sterols from C. longa should be focused, which could provide scientific basis for clarifying the quality marker (Q-marker) and quality evaluation research of C. longa.