Traditional uses, botany, phytochemistry, and pharmacology of Lonicerae japonicae flos and Lonicerae flos: A systematic comparative review.

ETHNOPHARMACOLOGICAL RELEVANCE: Lonicerae japonicae flos (LJF) and Lonicerae flos (LF) belong to different genera of Caprifoliaceae with analogous appearances and functions. Historically, they have been used as herbal medicines to treat various diseases with confirmed wind-heat evacuation, heat-clearing, and detoxification effects. However, the Chinese Pharmacopoeia (2005 Edition) lists LJF and LF under different categories. AIM OF THE STUDY: Few studies have systematically compared the similarities and dissimilarities of LJF and LF concerning their research achievements. This systematic review and comparison of the traditional use, identification, and phytochemical and pharmacological properties of LJF and LF provides valuable insights for their further application and clinical safety. MATERIALS AND METHODS: Related document information was collected from databases that included Web of Science, X-MOL, Science Direct, PubMed, and the China National Knowledge Infrastructure. RESULTS: The chemical constituents and pharmacological effects of LJF and LF were similar. A total of 337 and 242 chemical constituents were isolated and identified in LJF and LF, respectively. These included volatile oils, cyclic ether terpenes, flavonoids, phenolic acids, triterpenoids, and their saponins. Additionally, LJF plants contain more iridoids and flavonoids than LF plants. The latter have a variety of triterpenoid saponins and significantly higher chlorogenic acid content than LJF plants. Pharmacological studies have shown that LJF and LF have various anti-inflammatory, antiviral, antibacterial, anti-endotoxic, antioxidant, anti-tumor, anti-platelet, myocardial protective, and hepatoprotective effects. CONCLUSIONS: This review was undertaken to explore whether LJF and LF should be listed separately in the Chinese Pharmacopoeia in terms of their disease prevention and treatment strategies. Although LJF and LF showed promising effects, their action mechanisms remains unclear. Specifically, their impact on gut microbiota, gastrointestinal tract, and blood parameters requires further investigation. These studies will provide the foundation for scientific utilization and clinical/non-clinical applications of LJF and LF, and the maximum benefits from their mutual use.

Anaphylactoid reactions induced by Shuanghuanglian injection and Shenmai injection and metabolomics analysis.

Introduction: Shuanghuanglian injection (lyophilized) (SHLI) is commonly used to treat respiratory tract infection. Shenmai injection (SMI) is mainly used to treat cardiovascular diseases. Despite their widespread clinical use, anaphylactoid reactions (ARs) induced by SHLI and SMI have been reported, which have attracted broad attention. However, the impact of ARs on metabolic changes and the underlying mechanisms are still unclear. Methods: ICR mice were used as model animals and were treated with normal saline, C48/80, SHLI and SMI, respectively. The behavior of mice, auricle blue staining and Evans Blue exudation were used as indexes to evaluate the sensitization of SHLI and SMI and determine the optimal sensitization dose. Anaphylactoid mice model was established based on the optimal dose and enzyme-linked immunosorbent assay (ELISA) was used to model verification. Afterwards, plasma samples of administered mice were profiled by LC-MS metabolomics and analyzed to evaluate the changes in metabolites. Results: High doses of both SHLI and SMI can induce severe anaphylactoid reactions while the reaction induced by SMI was weaker. A Partial Least-Squares Discriminant Analysis (PLS-DA) score plot indicated that following administration, significant metabolic changes occurred in mice. 23 distinct metabolites, including deoxycholic acid, histamine, and 5-hydroxytryptophan, were identified in the SHLI groups. 11 distinct metabolites, including androsterone, 17α-hydroxypregnenolone, and 5-hydroxyindoleacetate, were identified in the SMI groups. Meanwhile, different metabolic pathways of SHLI and SMI were predicted by different metabolites. The associated metabolic pathways include steroid hormone biosynthesis, tryptophan metabolism, histidine metabolism, arachidonic acid metabolism, nicotinate and nicotinamide metabolism, and primary bile acid biosynthesis. Conclusion: Study showed that both SHLI and SMI can induce varying degrees of anaphylactoid reactions, a positive correlation between response intensity and dose was observed. Metabolomics showed that SHLI and SMI may promote the simultaneous release of hormones and inflammatory factors by disturbing relevant metabolic pathways, while SMI may also inhibit the release of inflammatory factors in arachidonic acid metabolic pathway, indicating both pro-inflammatory and anti-inflammatory effects. This study will serve as a reference for developing a new approach to evaluate the safety of SHLI and SMI from perspective of susceptible drug varieties. However, ARs mechanism requires further verification.

Comparative polypharmacokinetics of nine anti-inflammatory components of Jinyinhua (Lonicerae Japonicae Flos) and Shanyinhua (Lonicerae Flos) in mice with p-xylene-induced ear edema / 数字中医药（英文）

@#【Objective】 To reveal the integral in vivo polypharmacokinetics (PPK) similarity or difference between Jinyinhua (Lonicerae Japonicae Flos, LJF) and Shanyinhua (Lonicerae Flos, LF), and provide reference for their clinical application. 【Methods】 The PPK model and its total quantum statistical moment similarity (TQSMS) method were used to compare the integral PPK profiles of nine components with anti-inflammatory efficacy (rutin, caffeic acid, chlorogenic acid, cryptochlorogenic acid, dispsacoside B, macranthoidin B, isochlorogenic acid A, isochlorogenic acid B, and isochlorogenic acid C) of LJF and LF. A total of 54 Specific Pathogen Free (SPF) grade Kunming (KM) mice were randomized into LJF group and LF group (n = 27), and each group was divided into nine subgroups (n = 3) according to different time points. Subsequently, mice model of p-xylene-induced ear edema was constructed by oral administration of LJF and LF. The concentrations of the nine anti-inflammatory components in plasma samples of the mice were determined by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). And the pharmacokinetics (PK) parameters of single component and the integral PPK parameters [total quantum statistical moment (TQSM) and TQSMS] of multiple components were calculated by Drug And Statistics (DAS) software and home-brew programs with Excel, respectively. 【Results】 There were significant differences in single-component PK parameters between LJF and LF (P < 0.05). Whereas, no significant differences were found in multi-component TQSM parameters, including total quantum zero moment (AUCT0-t, AUCT0-∞) and total quantum first moment (MRTT0-t, MRTT0-∞) for the total quanta (P > 0.05). Accordingly, single-component TQSMS varied from 0.220 4 to 0.968 9, and that for the total quanta was 0.828 4, suggesting no significant differences in the speed and extent of bioavailability between LJF and LF. Furthermore, in light of high TQSMS (0.828 4), the integral PPK profiles of the nine anti-inflammatory components of LJF and LF were similar under 90% confidence intervals. 【Conclusion】 The PPK model and its TQSMS method are appropriate and efficient to compare the similarity or difference of integral PPK profiles of multi-component herbal medicines. It is suggested in this research that LJF can be replaced with LF or vice versa for anti-inflammatory treatment.

Comparison of Essential Oils of Houttuynia cordata Thunb. from Different Processing Methods and Harvest Seasons Based on GC-MS and Chemometric Analysis.

Houttuyniae Herba (HH) refers to the dried aerial part of Houttuynia cordata Thunb. (DHC) or the fresh whole grass of Houttuynia cordata Thunb. (FHC), where DHC are harvested in summer and FHC around the year. However, harvest seasons and processing methods (i.e., medicinal parts and drying process) might affect the quality of HH. To compare the essential oils (EOs) of DHC and FHC and their two harvest seasons, GC-MS analysis combined with chemometric analysis was applied. The results showed that the oil yield of FHC (0.076 ± 0.030%) was higher than that of DHC (0.038 ± 0.029%), and oil yield was higher in summer than in autumn (0.044 ± 0.029% for DHC1, 0.036 ± 0.028% for DHC2, 0.084 ± 0.026% for FHC1, and 0.067 ± 0.033% for FHC2, respectively). Moreover, hierarchical cluster analysis (HCA) and principal component analysis (PCA) successfully distinguished the chemical constituents of DHC and FHC oils. Additionally, according to orthogonal partial least squares discriminant analysis (OPLS-DA), eleven components were selected as chemical markers for discriminating DHC and FHC, and two and four chemical markers for discriminating two harvest seasons of DHC and FHC, respectively. Among these markers, the average contents of α-pinene, limonene, ß-phellandrene, α-terpineol, 4-tridecanone, and ethyl decanoate were higher in FHC oils. In contrast, the average contents of nonanal, 1-nonanol, ß-cyclocitral, n-hexadecanoic acid, and octadecanol were higher in DHC oils. Additionally, the contents of 4-tridecanone and ethyl decanoate were both higher in DHC1 oils than in DHC2 oils. Moreover, the contents of ß-myrcene and ß-phellandrene were higher in FHC1 oils, while the contents of 2,6-octadien-1-ol, 3,7-dimethyl-, acetate, and (z)-phytol were higher in FHC2 oils. For these reasons, this study provides a scientific basis for quality control and clinical medication.

[Comparative analysis and research on composition of mulberry-sourced medicinal materials by fingerprint division total statistical moment method and information entropy].

The present work is to analyze the HPLC fingerprints of mulberry-sourced materials(Mori Ramulus, Mori Folium, Muri Cortex, Mori Fructus) using the fingerprint division total statistical moment method and information entropy, and to study the diffe-rences of the chemical components and the overall characteristics of the imprinting template in different parts of mulberry-sourced medicinal materials, so as to provide the basis for finding the effective substances in response to "homologous and different effect" of mulberry(Morus alba). The fingerprints of 24 batches of mulberry-related materials, such as Mori Ramulus, Mori Folium, Muri Cortex, Mori Fructus, were established, and the similarities and differences of the fingerprints were analyzed by calculating the division total statistical moment parameters and information entropy. The AUC_T, MCRT_T, VCRT_T and H values of 24 batches of mulberry-sourced materials were less than 0.05, with significant difference. Among them, all samples showed absorption peaks within 3-11, and 20-24 min, indicating that the four types had the identical or similar chemical composition in the same time period. After 34 min, none of the four types showed absorption peaks. Greater VCRT_T value of the fingerprints of the four kinds was observed at the retention time ranges of 3-4, 16-18, 25-27, and 31-32 min, indicating that the components of the four kinds were significantly different in these time periods; and VCRT_T value of the mulberry was significantly higher than that of the other three kinds of medicinal materials at the retention time windows of 3-4 and 15-17 min; the VCRT_T value of the mulberry white skin was significantly higher at the time windows of 8-10 and 28-30 min; the VCRT_T value of all four kinds was significantly higher within 21-23 min, indicating that the four herbs contain the same or similar components in the chromatogram during this period, but there may be significant differences between the content and the proportion. In addition, the information entropy of mulberry branches is the largest at 7-12, 23-27 min, and that of mulberry fruits is the largest at 2-8 min, which indicates that the components of mulberry branches and mulberry fruits respond greatly in the corresponding period of time, which is also the main peak period of their chemical components. For the chemical components and corresponding efficacy here. The results showed that there are significant differences in the components and contents of mulberry-sourced medicinal materials. The division total statistical moment and information entropy of the total amount of segments can be used to analyze the differences in the components of "homology and different effects", which could provide a more comprehensive analysis method for the determination of quality markers.

[Research status of common processing technology of traditional Chinese medicine "maintaining medicinal properties after carbonisatus" and supramolecular "imprinting template" characterization technology].

Based on the characteristics of biological supramolecules and the law of " imprinting template",the research status and common problems in " maintaining medicinal properties after carbonisatus" in traditional Chinese medicine( TCM) were analyzed,and the further countermeasures were put forward. According to the historical evolution of " maintaining medicinal properties after carbonisatus" in TCM processing,the origin of its common problems was clarified by using the theory of biosupramolecular chemistry. TCM is a megacomplex biological supramolecular system,so TCM processing is just the processing of megacomplex biological supramolecular system,and its essence is a TCM pharmaceutical technology with chemical changes in host and guest of biological supramolecular system with or without adjuvant material under high temperature and humidity. In this study on pharmaceutical technology,host molecule was destructed in the process of carbonizing,but guest molecule was retained. The changing law of the host and guest molecule was controlled by the " imprinting template",which was reflected in the degree of change in the drug properties and efficacy of the decoction pieces. Supramolecular chemistry ran through the whole process,and the " imprinting template" of charcoal medicine was characterized by the supramolecular topological structure characteristics and imprinting behavior. After being combined with the quantitative mathematical model of heating degree in processing,it can realize the accurate processing of " maintaining medicinal properties after carbonisatus" from the source,quantitatively control the quality of carbonic herbs,and formulate stable and controllable quality standards.

A new similarity method for assessment of pharmacokinetic interaction between flucloxacillin and midazolam.

The purpose of this study was to develop a new similarity method to assess the drug-drug interaction between midazolam and flucloxacillin. Total quantum statistical moment (TQSM) of pharmacokinetic profiles were expressed by parameters AUCT, MRTT, VRTT et al. Statistical moment similarity (SMS) expressions were deduced to evaluate the similarity of the converted pharmacokinetic profiles. A trial of the pharmacokinetic interaction between midazolam and flucloxacillin by the SMS method was conducted. For midazolam, total quantum SMS (SMST) was 0.9582; total deviation was 0.0525; total variable probability was 4.18 %; total confidence of probability ß was 97.17 % under significance level 0.05; AUC0-∞ were 334.3±334.1 ng•h•mL-1 (after administration of midazolam alone) and 206.9±172.2 ng•h•mL-1 (after co-administration of midazolam and flucloxacillin), respectively. While, for 1'-hydroxy midazolam, SMST was 0.6920; total deviation was 0.3960; total variable probability was 30.80 %; total confidence of probability ß was 94.10 % under significance level 0.05; AUC0-∞ were 1364±810.7 ng•h•mL-1 (after administration of midazolam alone) and 1637±632.6 ng•h•mL-1 (after co-administration of midazolam and flucloxacillin), respectively. These results revealed that flucloxacillin might have weak pharmacokinetic interactions on midazolam metabolized into 1'-hydroxy midazolam, indicating that there was weak induction to CYP3A by flucloxacillin and that there was at least 30.80 % of metabolic behaviour in change with bioavailability decreased by 38.11 % that took effect to flucloxacillin metabolism for liver injury in CPY3A4 poor metabolic polymorphisms. SMS can be an optional method applied to characterize and analyze pharmacokinetic profiles.

[Screening of Shuanghuanglian Injection allergenic ingredients based on immune fingerprint].

In this paper,immune fingerprint was used to screen the allergenic components of Shuanghuanglian Injection(SHLI) by enzyme-linked immuno sorbent assay(ELISA) combined with HPLC/MS method. ELISA-embedded anti-IgE antibody could successfully adsorb allergens in SHLI and its plasma samples containing drugs through different routes of administration,suggesting that SHLI can induce type I hypersensitivity in rats. HPLC fingerprints and MS map of SHLI and drug-containing plasma samples from different routes of administration before and after anti-IgE antibody adsorption were established. According to the similarity evaluation of HPLC fingerprints and analysis results MS map,the sensitization of traditional Chinese medicine injections can be changed by different administration methods. There were 22 kinds of components that can be adsorbed by specific anti-Ig E antibodies in Shuanghuanglian Injection and its drug-containing plasma,most of them were acids and nitrogen compounds. Based on supramolecular theory,it was inferred that these compounds came from SHLI or body,and may form supramolecular hapten,which results in immunotoxicity and allergic reaction when being used as injection instead of oral liquid. Immune fingerprint is not only used to screen out single component allergen,but also more comprehensive,sensitive and easy to operate. It can provide reference for the future research methods of allergic reaction of traditional Chinese medicine injections.

[Dynamic chromatopharmacokinetics model for components in Chinese medicine and validation in Buyang Huanwu Decoction].

The Chinese medicine is mostly derived from plants or animals, highly polymorphic, with dynamic components which are reflected by the characteristic peaks and fingerprint peaks in chromatographic fingerprints. The chromatopharmacokinetics method for determined components is not applicable due to dynamic changes of chromatopharmacokinetics. Based on the preliminary study, dynamic pharmacokinetics mathematical model for multiple components in Chinese medicine was set up and verified by Buyang Huanwu Decoction as the model drug, applying the principle of the total quantum statistical moment(TQSM), superimposing or subtracting the relevant statistical parameters in blood samples and blank samples. This provided a new method for the chromatopharmacokinetic study of Chinese medicine. HPLC was used to determine the TQSM parameters in blood and blank sample fingerprints of Buyang Huanwu Decoction at each point, and the overall TQSM parameters of drug-containing blood sample and blank samples were obtained with addition calculation of TQSM; while the initial TQSM of the pure drug can be obtained with subtraction calculation. The metabolic and absorption equilibrium constants were calculated iteratively to a steady state using the estimated metabolic equilibrium constants, then the metabolic chromatopharmacokinetic parameters in rats were obtained: VUC_T 1.262×10~8 mAu·s, MRT_T 37.48 h, VRT_T 9.016×10~2 h~2, CL_T 25.79 mL·h~(-1)·kg~(-1), Vs 1.586×10~2 mL·kg~(-1), t_(T,0.5) 6.15 h, respectively. This suggested that 95% of the compounds in whole recipe were metabolized and secreted from the body after 0-96.33 h. The experiment verified that the established mathematical model and the total quantum moment statistics parameters can represent the dose-time relationship of Buyang Huanwu Decoction, which can be used to study on in vivo metabolism dynamics for Chinese medicine.

[Ginseng prescription rules and molecular mechanism in treating coronary heart disease based on data mining and integrative pharmacology].

The ancient dragon Materia Medica, Compendium of Materia Medica and other works recorded that the main effect of ginseng is tonifying qi. It is reported that the main active ingredient of ginseng is ginsenoside. Modern studies have found that ginseng mono saponins are effective for cardiovascular related diseases. This paper preliminary clarified the efficacy of traditional ginseng-nourishing qi and cardiovascular disease through the traditional Chinese medicine (TCM) inheritance auxiliary platform and integration platform of association of pharmacology. With the help of TCM inheritance auxiliary platform-analysis of "Chinese medicine database", Chinese medicine treatment of modern diseases that ginseng rules, so the traditional effect associated with modern medicine and pharmacology; application integration platform enrichment analysis on the target of drug and gene function, metabolic pathway, to further explore the molecular mechanism of ginseng in the treatment of coronary heart disease, aimed at mining the molecular mechanism of ginseng in the treatment of coronary heart disease. Chinese medicine containing ginseng 307 prescriptions, 87 kinds of disease indications, western medicine disease Chinese medicine therapy for ginseng main coronary heart disease; analysis of molecular mechanism of ginseng pharmacology integration platform for the treatment of coronary heart disease. Ginsenosides（Ra1, Ra2, Rb1, Rb2, Rg1, Ro) bind these targets, PRKAA1, PRKAA2, NDUFA4, COX5B, UQCRC1, affect chemokines, non-alcoholic fatty liver, gonadotropin, carbon metabolism, glucose metabolism and other pathways to treat coronary heart disease indirectly. The molecular mechanism of Panax ginseng's multi-component, multi-target and synergistic action is preliminarily elucidated in this paper.

Novel mathematic models for quantitative transitivity of quality-markers in extraction process of the Buyanghuanwu decoction.

BACKGROUND: Nowadays, to research and formulate an efficiency extraction system for Chinese herbal medicine, scientists have always been facing a great challenge for quality management, so that the transitivity of Q-markers in quantitative analysis of TCM was proposed by Prof. Liu recently. In order to improve the quality of extraction from raw medicinal materials for clinical preparations, a series of integrated mathematic models for transitivity of Q-markers in quantitative analysis of TCM were established. Buyanghuanwu decoction (BYHWD) was a commonly TCMs prescription, which was used to prevent and treat the ischemic heart and brain diseases. In this paper, we selected BYHWD as an extraction experimental subject to study the quantitative transitivity of TCM. STUDY DESIGN: Based on theory of Fick's Rule and Noyes-Whitney equation, novel kinetic models were established for extraction of active components. Meanwhile, fitting out kinetic equations of extracted models and then calculating the inherent parameters in material piece and Q-marker quantitative transfer coefficients, which were considered as indexes to evaluate transitivity of Q-markers in quantitative analysis of the extraction process of BYHWD. METHODS: HPLC was applied to screen and analyze the potential Q-markers in the extraction process. Fick's Rule and Noyes-Whitney equation were adopted for mathematically modeling extraction process. Kinetic parameters were fitted and calculated by the Statistical Program for Social Sciences 20.0 software. The transferable efficiency was described and evaluated by potential Q-markers transfer trajectory via transitivity availability AUC, extraction ratio P, and decomposition ratio D respectively. The Q-marker was identified with AUC, P, D. RESULTS: Astragaloside IV, laetrile, paeoniflorin, and ferulic acid were studied as potential Q-markers from BYHWD. The relative technologic parameters were presented by mathematic models, which could adequately illustrate the inherent properties of raw materials preparation and affection of Q-markers transitivity in equilibrium processing. AUC, P, D for potential Q-markers of AST-IV, laetrile, paeoniflorin, and FA were obtained, with the results of 289.9 mAu s, 46.24%, 22.35%; 1730 mAu s, 84.48%, 1.963%; 5600 mAu s, 70.22%, 0.4752%; 7810 mAu s, 24.29%, 4.235%, respectively. CONCLUSION: The results showed that the suitable Q-markers were laetrile and paeoniflorin in our study, which exhibited acceptable traceability and transitivity in the extraction process of TCMs. Therefore, these novel mathematic models might be developed as a new standard to control TCMs quality process from raw medicinal materials to product manufacturing.

A novel concept of Q-markers: Molecular connectivity index.

BACKGROUND: Drugs derived from botany have been playing essential role in both clinical treatment and pharmaceutical industry, unfortunately our worry is still that its quality and therapeutic efficacy are inconsistent. Recently many scientists launched a new project on quality (Q)-marker of medicinal herbs, this study was thus designed to generate a novel concept of quality (Q)-markers: molecular connectivity index (MCI), and to test and verify the new concept of molecular connectivity index (MCI). METHODS: The first-order term (1χ) was selected to calculate and study quality (Q)-marker for TCM. Houttuynia cordata Thunb. (HCT) was adopted as a model to verify the hypothesis. Volatile oils of HCT were determined using gas chromatography-mass (GC-MS). SIMCA 13.0 and SPSS 21.0 were used to deal with the data. RESULTS: The minimum of the MCI values was 1.273, belonging to the peak 15, but the maximum (12.822) belonged to the peak 34, and the average value of fifty volatile oils was 5.798. The results demonstrated that MCI was the principle component, and monoterpenoid and sesquiterpenoid were also the principle components in oils. Fig. 2a shows peak 5, 24, 34 were the significant ingredients, while Fig. 2b shows peak 2, 5, 24 were the significant components. CONCLUSION: The data demonstrated that MCI was associated with the structure of molecules and the therapeutic efficacy, MCI could directly exhibit the relationship between ingredients and effectiveness of Traditional Chinese Medicine (TCM). So MCI could be a potential and promising parameter for quality (Q)-marker. Therefore, MCI may be developed as a novel potential concept to control the quality of TCM.

Application of TQSM polypharmacokinetics and its similarity approach to ascertain Q-marker by analyses of transitivity in vivo of five candidates in Buyanghuanwu injection.

BACKGROUND: It is well-known that the public still have been facing on a severe issue about the inconsistency of quality and therapeutic efficacy of traditional medicines. Recently, Professor Chang-Xiao Liu has created a new promising concept for identifying relevant quality-markers (Q-marker) from herbs, their formulas and manufacturing products. Therefore, building up a new approach is necessary for us to bridge over quality to efficacy of pharmaceutical products. STUDY DESIGN: In this paper, five candidate Q-markers, astragaloside IV, paeonflorin, amygdalin, tetramethylpyrazine, ferulic acid in Buyanghuanwu injection (BYHWI) had been designed to carry out in rat by using single and polypharmacokinetic models for total quanta to ascertain adequate Q-marker. METHODS: The Q-marker transitivity in vivo was studied with polypharmacokinetic model and its similarity approach, which were modeled with TQSM principle. The Q-marker was ascertained with transitive similarity and bioavailability in polypharmacokinetics. Their concentrations in plasma sample of white rat were determined by RP-HPLC. Data analyses were used by the DAS software for singles and myself-written-program with EXCEL for multiples. RESULTS: In BYHWI, five candidate Q-marker pharmacokinetic profiles were singly fixed to two compartmental models in rat using classical compartmental analysis, but there were tremendous differences among which the candidate parameters were fluctuated from nearly 3552 folds to equivalency. The theoretical value of TQSM polypharmacokinetic parameters such as AUCT, MRTT, VRTT, CLT, VT over the mixure of five drugs were 110.8 ±â€¯51.91 mg min ml-1, 176.0 ±â€¯36.5 min, 39,921 ±â€¯4311 min2, 0.3116 ±â€¯0.02347 ml min-1 kg-1, 54.83 ±â€¯7.683 ml kg-1 respectively. The TQSM polypharmacokinetic parameters in astragaloside Ⅳ ordered by AUCT, MRTT, VRTT, CLT, VT were 110.8 ±â€¯51.91 mg min ml-1, 176.0 ±â€¯36.5 min, 39,921 ±â€¯4311 min2, 0.3116 ±â€¯0.02347 ml min-1 kg-1, 54.83 ±â€¯7.683 ml kg-1, respectively, which were closed to the theoretical values. TQSM similarity versus astragaloside Ⅳ was 0.9661. CONCLUSION: The results represented that the optimum Q-marker in BYHWI is astragaloside Ⅳ, whose transitivity in vivo similarity was close to the behavior of polypharmacokinetics with maximum bioavailability to the total quanta. It is feasible for Q-marker in CMMs to screen on the comparison of single pharmacokinetic behavior and bioavailability to the total quanta.

[Analysis on property of meridian supramolecules by biological evolution path].

With human placed in the whole nature, by following the biologic evolution path, the property of channel structure for "imprinting template" in meridian and zang-fu was explored with supramolecular chemistry. In the history of biologic evolution, each molecule in "molecule society" gradually developed into various highly-ordered supramolecular bodies based on self-identification, self-assembly, self-organization, self-replicating of"imprinting template", and thereby the original biochemical system was established, and finally evolved into human. In the forming process of supramolecular bodies, the channel structure of"imprinting template" in guest supramolecular bodies would be kept by host supramolecular bodies, and communicate with the outside to exchange materials, energy, information, otherwise life phenomenon could not continue, for which it was the chemical nature of biolo-gical supramolecular bodies for body to develop meridian. Therefore, the human was a gigantic and complicated supramolecules body in biological nature, and possessed the supramolecules "imprinting template" at each stage of evolution, for which the meridians were formed. When meridians converged, acupoints appeared; when acupointsconverged, zang-fu appeared. With the promotion of the blood from heart, according to"imprinting template", the guest supramolecular bodies and host meridian produced qi-analysis, which was the qi-phenomenon of guest in meridian. It presented as zang-fu image of physiology and pathology as well as action regularities of medication and acupuncture tolerance, by which current various meridian viewpoints could be explained and propose the hypothesis of meridian supramolecular bodies. The meridian and its phenomenon was decide by its "imprinting template" of supramolecular bodies and self-reaction regularities, which abided through the living nature. This was the substance for meridian biology.

[Characteristics of supramolecular imprinting template on liver meridian tropism of traditional Chinese medicine based on molecular connectivity index].

The molecular connectivity index was adopted to explore the characteristics of supramolecular imprinting template of herbs distributed to liver meridian, in order to provide scientific basis for traditional Chinese medicines(TCMs) distributed to liver meridian. In this paper, with "12th five-year plan" national planning textbooks Science of Traditional Chinese Medicine and Chemistry of Traditional Chinese Medicine as the blueprint, literatures and TCMSP sub-databases in TCM pharmacology of northwest science and technology university of agriculture and forestry were retrieved to collect and summarize active constituents of TCM distributed to liver meridian, and calculate the molecular connectivity index. The average molecular connectivity index of ingredients distributed to liver meridian was 9.47, which was close to flavonoid glycosides' (9.17±2.11) and terpenes (9.30±3.62). Therefore, it is inferred that template molecule of liver meridian is similar to physicochemical property of flavonoid glycosides and terpenes, which could be best matched with imprinting template of liver meridian.

[Q-marker of Chinese medicine and metabolic regularity of co-network compatibility and rainbow potential].

The effect of Chinese medicine (CM) compound prescription is the combined action results of single herbs based on the basic theory of Chinese medicine, and its function embodies the characteristics of multi components, multi targets and comprehensive effects. It is difficult to study the therapeutic material, establish quality standards or determine Q-marker, so we can't strictly monitor the quality of the whole process of CM. The identification of Q-marker has a profound influence on the whole process of the pharmaceutical engineering of CM. The scattered effect of CM multi-components is regarded as the integral action of the parent nucleus group by the metabolic rule of co-network compatibility and rainbow potential (CCRP). The rule can be used to communicate the individual components and macro components, to reveal the metabolism of CM in organism body and basic law of information exchange, thus revealing the action law of CM on human body. Through the systematic analysis of the Q-marker's guidance to the development of CM and its relationship with the metabolic rule of CCRP, we try to provide some ideas for the identification of Q-marker.

Study design and implementation for population pharmacokinetics of Chinese medicine: An expert consensus.

Although many population pharmacokinetics (PPK) researches have been conducted on chemical drugs, few have been in the field of Chinese medicine (CM). Each ingredient in CMs possesses different pharmacokinetic characteristics, therefore, it is important to develop methods of PPK studies on them to identify the differences in CM drug safety and efficacy among the population subgroups and to conduct quantitative studies on the determinants of CM drug concentrations. To develop an expert consensus on study design and implementation for PPK of CM, in August 2013, 6 experts in the field of PPK, CMs pharmacology, and statistics discussed problems on the PPK research protocol of CMs, and a consensus was reached. The medicines with toxicity and narrow therapeutic windows and with wide range of target population or with frequent adverse reactions were selected. The compositions with definite therapeutic effects were selected as indices, and specific time points and sample sizes were designed according to standard PPK design methods. Target components were tested through various chromatography methods. Total quantity statistical moment analysis was used to estimate PPK parameters of each component and PPK models reflecting the trend of CMs (which assists in reasonable adjustments on clinical dosage). This consensus specifies the study design and implementation process of PPK. It provides guidance for the following: post-marketing clinical studies, in vivo investigations related to the metabolism in different populations, and development and clinical adjustment of dosages of CMs.

[Impact of ″imprinting templates″ characteristics of traditional Chinese medicine injection supramolecules on (anaphylactoid) hypersensibility].

The (anaphylactoid) hypersensibility mechanism of ″imprinting templates″ characteristics of traditional Chinese medicine (TCM) injection supramolecules was clarified to lay the foundation to build safety evaluation method. Based on the previous publication on special impact of Chinese medicine theories on supramolcular chemistry, combined with the natural origination of (anaphylactoid) hypersensitized special rules as well as the sensitization phenomenon of cordate houttuynia injection, the impact of the structure characteristics of ″imprinting templates″ in TCM injection supramolecules on its (anaphylactoid) hypersensibility was clarified. In Chinese medicine injections, the supramolecular structures can independently be generated, showing overall apparent (anaphylactoid) hypersensibility nature, and their structure characteristics were dependent on the strength. In addition, (anaphylactoid) hypersensitive critical supramolecular structure was present. When it was administrated by ″injection″, it's structure was not easy to be destroyed, often showing apparent immunogenicity, whereas if it was administrated by ″oral″, the structure would be destroyed by the gastrointestinal tract, showing weaker or no apparent immunogenicity. Therefore, there are differences in (anaphylactoid) hypersensibility between ″injection″ and ″oral″ administration of TCM. TCM injections would produce the supramolecules between ″molecular society″ by independent reaction of supramolecular ″imprinting template″ (chemical determinants), showing apparent immune process of recognition, copying, and storage. Single molecule is a special example for this. The screening of anaphylactoid (sensitinogen) includes the single ingredients and their forming supramolecules for TCM injection. This is the unique feature for safety evaluation of Chinese medicine injection.

[Chinese medicine preparation supramolecular imprinting templates based on in vitro release characteristics of BYHW sustained-release tablet].

The study focused on the in vitro release of Buyanghuanwu (BYHW) elementary osmotic pump sustained release tablets. Its band similarity was calculated by the total quantum statistical moment. Meanwhile, in vitro release characteristics were analyzed to discuss the existence of supramolecular imprinting templates. The results show that the same imprint templates may exist in different structures of traditional Chinese medicine(TCM)'s multi-components. The BYHW sustained release tablets prepared by elementary osmotic pump can meet the objectives of "overall control, synchronous release". However, the supramolecular imprinting templates in TCM compound prescriptions should be further explored, the overall and synchronous release of different components was controlled through imprinting templates, so as to seek the more suitable sustained release preparation technology for multiple components of TCM, and make it in line with the characteristics of TCM.

[Dispute for Japanese(wild) honeysuckle flower based on supermolecular imprinting templates].

More and more disputes have happened to confront us continuously since the separation of Japanese(wild) honeysuckle flower in Chinese Pharmacopoeia in 2005. The state pharmacopeia committee decided to separate Japanese(wild) honeysuckle flower into two species for japanese(wild) honeysuckle flower, but didn't define their the convincing reasons still did not provide to us as a result that two medicines are not described the differences in natural properties, efficiency and indication, usage and dosage, as well as not given a resolving methodand specific solution. It was known for us that in the history of traditional Chinese medicine（TCM）, the phenomenenphenomena of the "one drug from multi-species" and "one species for multi-drug" are very ordinary thingswere ubiquitous. Whether separation of the drug species are separated shall be decided to by clinical efficiency. Through Chinese pharmacopoeia (2015 edition) issue of Chinese Pharmacopoeia the 2015 issue of the Chinese Pharmacopoeia, we still cannot find a scientific solution for the dispute of for Japanese (wild) honeysuckle flower, perhaps because of insufficient reorganization of TCM clinical medication regularities, such as "treatment of different diseases with same drug", " treatment of the same disease with different drugs" and "treatment of the same syndrome with multi-prescriptions", and "one prescription treating multiple syndromes"; lack of in-depth analysis for multi-component TCM compounds and autonomisation of "supermolecular template" for organs and meridians; less attention to the advance of efficacy and safety evaluation technologies for multi-component TCM compounds; impacts from the medication mode of "one ingredient-one composition-one effect"; as well as insufficient research methods for bioequivalent evaluation in preclinic and clinic studies . The dispute for species combination or separation for Japanese(wild) honeysuckle flower was apparently caused by regional economy, drug biological equivalent of efficacy and safety, but arising from clinical principles for systematical syndrome treatment with TCM, or concepts in the treatment of diseases with TCM or western medicines. This paper focused on current studies on Japanese(wild) honeysuckle flower in the combination with TCM clinical medication regularities, such as "treatment of different diseases with same drug", "treatment of the same disease with different drugs" and "treatment of the same syndrome with multi-prescriptions", and "one prescription treating multiple syndromes", expounded the specific pharmacological regularity of "heterogeneous equivalence" of Japanese (wild) honeysuckle flower, and put forward methods for studying bioequivalence of Japanese(wild) honeysuckle flower, in order to solve the combination and separation of Japanese(wild) honeysuckle flower and lay a foundation for promoting the development of Chinese herbal medicine industry.