Development of organic three-phase laminar flow microfluidic chip for extraction of ginsenosides from Panax ginseng.

BACKGROUND: Herbal extracts contain multiple active constituents, so the sample preparation based on the liquid-liquid extraction (LLE) is demanding, especially when a study subsequent to extraction is needed. Since the laminar flow occurring in microchannels can be formed between two miscible organic phases, a new method of extracting polar compounds from the crude extract of Panax ginseng Meyer in aqueous ethanol by pure n-butanol in the three-phase laminar flow microfluidic chip was established. METHODS: A new chip consisting of long microchannels with a guide structure was employed to improve the extraction efficiency caused by the low diffusion ability of saponins. The method was evaluated by using the extraction yields and purities of ginsenosides Rg1, Re and Rb1 as the indicators, and extraction conditions such as flow rate, temperature and other governing factors were optimized. RESULTS: Using the new chip method, the extraction efficiencies of ginsenoside Rg1, Re and Rb1 were 63.1%, 69.5% and 71.6%, respectively, which are higher than the 26% achieved in a previous report. The extraction yields of 1.53, 0.51, 0.90 mg/g were also higher than those obtained previously by the successive laminar flow microchip method. CONCLUSION: The proposed new microfluidic chip method has simplified the sample pretreatment steps to improve the yield of ginsenoside extraction from ginseng samples.

Identifying the active ingredients of carbonized Typhae Pollen by spectrum-effect relationship combined with MBPLS, PLS, and SVM algorithms.

Typhae Pollen (TP) and its carbonized product (carbonized Typhae Pollen, CTP), as cut-and-dried herbal drugs, have been widely used in the form of slices in clinical settings. However, the two drugs exhibit a great difference in terms of their clinical efficacy, for TP boasts an effect of removing blood stasis and promoting blood circulation, while CTP typically presents a hemostatic function. Since the active ingredients of CTP, so far, still remain unclear, this study aimed at identifying the active ingredients of CTP by spectrum-effect relationship approach coupled with multi-block partial least squares (MBPLS), partial least squares (PLS), and support vector machine (SVM) algorithms. In this study, the chemical profiles of a series of CTP samples which were stir-fried for different duration (denoted as CTP0∼CTP9) were firstly characterized by UHPLC-QE-Orbitrap MS. Then the hemostatic effect of the CTP samples was evaluated from the perspective of multiple parameters-APTT, PT, TT, FIB, TXB2, 6-keto-PGF1α, PAI-1 and t-PA-using established rat models with functional uterine bleeding. Subsequently, MBPLS, PLS and SVM were combined to perform spectrum-effect relationship analysis to identify the active ingredients of CTP, followed by an in vitro hemostatic bioactivity test for verification. As a result, a total of 77 chemical ingredients were preliminarily identified from the CTP samples, and the variations occurred in these ingredients were also analyzed during the carbonizing process. The study revealed that all the CTP samples, to a varying degree, showed a hemostatic effect, among which CTP6 and CTP7 were superior to the others in terms of the hemostatic effect. The block importance in the projection (BIP) indexes of MBPLS model indicated that flavonoids and organic acids made more contributions to the hemostatic effect of CTP in comparison to other ingredients. Consequently, 9 bioactive ingredients, including quercetin-3-O-glucoside, kaempferol-3-O-rutinoside, quercetin, kaempferol, isorhamnetin, 2-methylenebutanedioic acid, pentanedioic acid, benzoic acid and 3-hydroxybenzoic acid, were further identified as the potential active ingredients based on PLS and SVM models as well as the in vitro verification. This study successfully revealed the bioactive ingredients of CTP associated with its hemostatic effect, and also provided a scientific basis for further understanding the mechanism of TP processing. In addition, it proposed a novel path to identify the active ingredients for Chinese herbal medicines.

Acupuncture for gait disturbance of patients with subacute and chronic stroke: a systematic review and meta-analysis protocol.

INTRODUCTION: Hemiparetic gait is one of the most common sequelae of a stroke. Acupuncture has shown potential in correcting hemiplegic gait patterns and improving motor function recovery after stroke. However, controversial findings and a lack of supportive evidence on the effectiveness of acupuncture for post-stroke hemiplegia. The intelligent gait analysis system provides a new perspective for the study of hemiparetic gait. This systematic review aims to collect relevant studies and critically evaluate the efficacy and safety of acupuncture in alleviating gait disturbance of post-stroke hemiplegia based on quantified gait parameters. METHODS AND ANALYSIS: A comprehensive search of PubMed, Embase, Cochrane stroke group trials register, Cochrane Central Register of Controlled Trials, CINAHL, AMED, three Chinese databases (Chinese Biomedical Literatures database (CBM), National Knowledge Infrastructure (CNKI), and Wan fang Digital Periodicals), four trails registries (The WHO International Clinical Trials Registry Platform, The Chinese Clinical Trial Registry, The US National Institutes of Health Ongoing Trials Register, and The Australian New Zealand Clinical Trials Registry) will be conducted to identify randomised controlled trials of acupuncture for gait disturbance in post-stroke patients. No restrictions on language or publication status. The primary outcomes are gait temporospatial parameters (eg, step length, stride length, step width, step frequency (cadence), walking speed, etc), and gait kinematic parameters (eg, hip peak flex/extend angle, knee peak flex/extend angle, ankle peak dorsi/plantar-flexion angle, etc). We will assess bias using the approach recommended by the Cochrane Handbook for Systematic Reviews of Interventions. A meta-analysis will be conducted to synthesise the evidence for each outcome measure. The χ2 test and I2 statistic will be used for assessing heterogeneity between studies. ETHICS AND DISSEMINATION: No ethical approval is needed because no primary data is collected. Scientific conferences or peer-reviewed journals will publish the findings. PROSPERO REGISTRATION NUMBER: CRD42022384348.

A network pharmacology integrated pharmacokinetics strategy to investigate the pharmacological mechanism of absorbed components from crude and processed Zingiberis Rhizoma on deficiency-cold and hemorrhagic syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: Zingiberis Rhizoma (ZR) and Zingiberis Rhizoma Carbonisata (ZRC), as two forms of ginger-based herbal drugs used in China for at least 2000 years, have been recorded in Chinese Pharmacopoeia and applied for specific indications in traditional Chinese medicine (TCM). AIM OF THE STUDY: The present study aimed to explore the underlying therapeutic and processing mechanism of the absorbed components of ZR and ZRC on deficiency-cold and hemorrhagic syndrome (DCHS) using network pharmacological technique combined with pharmacokinetics strategy. MATERIALS AND METHODS: In this study, a rapid and sensitive approach was conceived to simultaneously determine the seven components (zingiberone, 6-gingerol, 8-gingerol, 6-shogaol, 6-paradol, diacetyl-6-gingerol and 10-gingerol) in rat serum by HPLC-DAD-MS. The network pharmacological technique was employed to evaluate the effect of the absorbed components of ZR and ZRC on DCHS. Also, the vitro experiments were carried out to validate the functions of the seven compounds on coagulation and other major haematological effects. RESULTS: The values of intra-assay and inter-assay precision were determined to be less than 7.44%, with an accuracy value ranging from 83.64% to 107.99%. Analysis of rat plasma revealed that the extraction recoveries and matrix effects of the seven analytes were >85.76%. The method for validation following oral administration of ZR and ZRC to rats was proved to be a success in the pharmacokinetic study of the seven ingredients. Pharmacokinetics showed that ZR processing could enhance the absorption and utilization of 6-shogaol, 6-paradol and diacetyl-6-gingerol, meanwhile reduce the absorption of 6-gingerol, 8-gingerol, and 10-gingerol. Through the pathway enrichment analysis, it was found that the significant biological process of ZR and ZRC on DCHS was primarily associated with complement, coagulation cascades and platelet activation pathways. The vitro experiments indicated that zingiberone, 6-paradol and diacetyl-6-gingerol had a hemostatic effect by upregulating the expression of one or more targets such as TNF-α, FⅩa, FⅫ, FⅧ, ICAM-1, vWF and ITGB3. While 6-gingerol, 6-shogaol, 8-gingerol and 10-gingerol played a critical role in promoting blood circulation by increasing the expression of TM and/or PORC, and/or reducing the expression of ITGB3. CONCLUSION: In brief, network pharmacological technique in combination with pharmacokinetics strategy provided an applicable method for pharmacological mechanism study of ZR and ZRC, which, also, could be used as reference for quality control of the two drugs. In a broader sense, this combined strategy might even be valuable in uncovering the therapeutic and processing mechanism of Chinese herbs on a systematic level.

[Mechanism and protocol optimization of acupuncture in treatment of obesity based on sympathetic nerve system].

The physiological function of adipose tissue is dominated by the sympathetic nerve system (SNS), but obesity and other diseases may cause the abnormality of the SNS signaling pathway. Acupuncture has been proved to be an effective the-rapy to improve the function of SNS in adipose tissue. Based on the physiological and pathological significance of SNS, this paper reviewed the molecular pathways in which acupuncture directly or indirectly regulated the function of SNS in adipose tissue. As the mechanism of electroacupuncture in regulating autonomic nerves was continuously illuminated, the adjustment of acupuncture mode, such as selection of acupoints in different nerve segments and adjustment of stimulation parameters of electroacupuncture, presumedly induced different content ratios of neurotransmitters released by SNS efferent axons, including noradrenaline and neuropeptide Y, thereby producing different effects on weight loss. Therefore, the specific connections between various acupuncture modes and neurotransmitters released by SNS enriched the intrinsic nerve coding of acupoints, thus optimizing the acupoint selection protocol for the treatment of obesity.

Discrimination and chemical composition quantitative model of Raw Moutan Cortex and Moutan Cortex Carbon based on electronic nose and machine learning.

Raw Moutan Cortex (RMC) is a traditional medicinal material commonly used in China. Moutan Cortex Carbon (MCC) is a processed product of RMC by stir-frying. As raw and processed products of the same Chinese herb pieces, they have different effects. RMC has the effects of clearing heat and cooling blood, promoting blood circulation and removing blood stasis, but MCC has the contrary effect of cooling blood and hemostasis. Therefore, it is necessary to distinguish them effectively. The traditional quality evaluation method of RMC and MCC still adopts character identification, and mainly relies on the working experience and sensory judgment of employees with experience. This will lead to strong subjectivity and poor repeatability. And the final evaluation result may cause inevitable errors and the processed products with different processing degrees in actual production, which affects the clinical efficacy. In this study, the electronic nose technology was introduced to objectively digitize the odor of RMC and MCC. And the discrimination model of RMC and MCC was constructed in order to establish a rapid, objective and stable quality evaluation method of RMC and MCC. According to the correlation analysis, the experiment found the content of gallic acid, 5-hydroxymethylfurfural (5-HMF), paeoniflorin and paeonol determined by high performance liquid chromatography (HPLC) had a certain correlation with their odor characteristics. Thus, partial least squares regression (PLSR) and support vector machine regression (SVR) were compared and established the chemical composition quantitative model. Results showed that the quantitative data of RMC and MCC odor could be used to predict the contents of the chemical components. It can be used for quality control of RCM and MCC.

UPLC-Q-Exactive/MS-based metabonomics revealed protective effect of Zingiberis rhizome and its processed product on deficiency-cold and hemorrhagic syndrome rats.

Zingiberis rhizome carbonisata (ZRC) is the processed product of Zingiberis rhizome (ZR). ZR is mainly used for warming the spleen and stomach to dispel cold, whereas ZRC is commonly applied as a treatment for deficiency-cold and hemorrhagic syndrome (DCHS). Although they have long been used to serve different clinical purposes, the specific action mechanism of the drugs and molecular changes underlying ZR processing are not clear. In this study, metabolomics study was carried out to analyze the alterations in endogenous metabolites in serum and urine samples of DCHS rat models using ultra-high-performance liquid chromatography coupled with quadrupole-Exactive mass spectrometry technique and constructed principal component analysis score plots that showed that the ZRC group was completely separated from the DCHS and ZR groups but demonstrated a highly close plotting to the normal control group. The results revealed that both ZR and ZRC intervened in the metabolic pathways of DCHS models but to varying degrees and with different influencing factors. In addition, ZRC was found to function as a treatment for the metabolic disorders of DCHS through 15 pharmacodynamic biomarkers involving a series of pathways, such as glycine, serine, and threonine metabolic pathway, as well as arachidonic acid metabolic pathways. This study showed that metabolomics method based on ultra-high-performance liquid chromatography coupled with quadrupole-Exactive mass spectrometry could preliminarily illuminate the therapeutic mechanism of ZR and ZRC on DCHS and the changes in ZR processing from the molecular-level perspective. The results also provided new insight into further research on DCHS treatment.

[Quality markers of Zingiberis Rhizoma Carbonisata before and after processing].

Based on the previous research results of our group and literature research, the chemical components, mechanisms, pharmacodynamics, and pharmacokinetics of Zingiberis Rhizoma Carbonisata were summarized to determine the quality markers(Q-markers) of Zingiberis Rhizoma Carbonisata and Zingiberis Rhizoma. Our research group has clarified the differential components of Zingiberis Rhizoma Carbonisata and Zingiberis Rhizoma, the meridian-warming hemostatic effect of Zingiberis Rhizoma Carbonisata, the related targets and pathways of the effect, the endogenous biomarkers of Zingiberis Rhizoma Carbonisata, and the hemodynamic processes of Zingiberis Rhizoma Carbonisata and Zingiberis Rhizoma. Moreover, based on high-performance liquid chromatography-diode array detector-electrospray ionization mass spectrometry(HPLC-DAD-ESIMS), a method for determining the content of Q-mar-kers was established. In conclusion, the study finally determined that gingerone, 6-shogaol, and diacetyl-6-gingerol were the Q-mar-kers of Zingiberis Rhizoma Carbonisata decoction pieces, and 6-gingerol, 8-gingerol, and 10-gingerol were Q-markers of Zingiberis Rhizoma decoction pieces. The result is expected to provide a reference for the establishment of quality standards for Zingiberis Rhizoma Carbonisata decoction pieces and Zingiberis Rhizoma decoction pieces.

Identifying of Anti-Thrombin Active Components From Curcumae Rhizoma by Affinity-Ultrafiltration Coupled With UPLC-Q-Exactive Orbitrap/MS.

Recent studies concerning products that originate from natural plants have sought to clarify active ingredients, which both explains the mechanisms of the function and aids in quality control during production. As a traditional functional plant, Curcumae Rhizoma (CR) has been proven to be effective in promoting blood circulation and removing blood stasis. However, the components that play a role in its huge compound library are still unclear. The present study aimed to develop a high-throughput screening method to identify thrombin inhibitors in CR and validate them by in vitro and in vivo experiments. The effect of CR on thrombin in HUVECs cells was determined by ELISA, then an affinity-ultrafiltration-UPLC-Q-Exactive Orbitrap/MS approach was applied. Agatroban and adenosine were used as positive and negative drugs respectively to verify the reliability of the established method. The in vitro activity of the compounds was determined by specific substrate S-2238. The in vivo effect of the active ingredients was determined using zebrafish. Molecular docking was used to understand the internal interactions between compounds and enzymes. ELISA results showed that CR had an inhibitory effect on thrombin. The screening method established in this paper is reliable, by which a total of 15 active compounds were successfully identified. This study is the first to report that C7, 8, and 11 have in vitro thrombin-inhibitory activity and significantly inhibit thrombosis in zebrafish models at a safe dose. Molecular docking studies were employed to analyze the possible active binding sites, with the results suggesting that compound 16 is likely a better thrombin inhibitor compared with the other compounds. Based on the affinity-ultrafiltration-UPLC-Q-Exactive Orbitrap/MS approach, a precisely targeted therapy method using bio-active compounds from CR might be successfully established, which also provides a valuable reference for targeted therapy, mechanism exploration, and the quality control of traditional herbal medicine.

[Analysis of volatile oil components of different species of Curcumae Rhizoma based on GC-MS and chemometrics].

The volatile oil of Curcumae Rhizoma has many active components,which are the key to the quality of Curcumae Rhizoma. Exploring the difference between volatile oil of different kinds of Curcumae Rhizoma facilitates the quality control and rational application of resources. In this study,GC-MS was applied to realize online qualitative and semi-quantitative analysis of the chemical composition spectrum of volatile oil from Curcuma wenyujin( CW),C. phaeocaulis( CP),and C. kwangsiensis( CK). Forty components were identified and their fingerprints were compared and evaluated. Hierarchical cluster analysis( HCA),principal component analysis( PCA),and orthogonal partial least squares discrimination analysis( OPLS-DA) were adopted to analyze the overall and outlier data. The results showed that the whole data could be divided into three kinds according to each analysis mode,and the volatile components of Curcumae Rhizoma vary greatly among species. PCA explored the difference between outliers and the mean value of the group and found that some volatile oils from CW may be greatly affected by the origin. By OPLS-DA,the samples from Zhejiang were able to gather,but those from Guizhou remained isolated,indicating the influence of growing environment on Curcumae Rhizoma metabolites. Based on VIP results combined with the heat map,characteristic volatile oil components of Curcumae Rhizoma from different varieties were screened out: curdione and linalool for CW; 2-undecanone for CP; humulene,γ-selinene,and zederone for CK. The GCMS method established in this study describes Curcumae Rhizoma samples comprehensively and accurately,and the characteristic components screened based on chemometrics can be used to distinguish Curcumae Rhizoma from different varieties and give them unique pharmacodynamic significance,which is fast,convenient,stable,and reliable and supports the rational application of Curcu-mae Rhizoma resources. It is found that the region of origin has great influence on CW,which is worthy of further study.

Screening of high-efficiency and low-toxicity antitumor active components in Macleaya cordata seeds based on the competitive effect of drugs on double targets by a new laminar flow chip.

It is urgent to obtain targeted drugs that selectively bind to pathological targets rather than physiological targets in the early stage of drug screening. G-Quadruplex has become one of the important targets in the development of anti-tumor drugs. However, drugs that target quadruplexes may also bind to dsDNA, which may lead to adverse reactions. In this study, a new three-phase laminar flow chip was constructed to enable the multi-components of a traditional Chinese medicine extract to dynamically and competitively bind with G-quadruplex DNA (on target) and double-stranded DNA (off target), so as to select high-efficiency and low-toxicity anti-tumor drugs. The results showed that there were five compounds in the extracts of Macleaya cordata seeds that exhibited obvious differences in binding to the two targets. Furthermore, the binding constants and modes of four identified alkaloids as they bound to two DNA targets were verified by fluorescence spectra and molecular docking methods. The toxicity to HepG2 and LO2 cells from the four alkaloids was also compared. The results showed that sanguinarine and chelerythrine could be used as candidate drugs with stronger binding to HT24 than DNA26. The chip can also be used for other types of double-target screening of other traditional Chinese medicine extracts or compound libraries.

iTRAQ-based quantitative proteomics and network pharmacology revealing hemostatic mechanism mediated by Zingiberis Rhizome Carbonisata in deficiency-cold and Hemorrhagic Syndrome rat models.

Zingiberis Rhizome Carbonisata (ZRC) has been used as a hemostatic agent in traditional Chinese medicine (TCM). However, the underlying molecular mechanism remains unclear. In this study, network pharmacology method was used to predict the potential mechanism of ZRC on hemostasis, based on the structures of the main compounds. Then, iTRAQ-based quantitative proteomics analysis was used for verification of the candidate target proteins and pathways to illustrate the underlying mechanisms. Furthermore, the differentially expressed proteins (DEPs) in the enriched pathways were validated by Enzyme-linked immunosorbent assay. The results showed that the hemostasis mechanism of ZRC may be related to Platelet activation, Rap1 signaling pathway and Complement and coagulation cascades. And 10 proteins (Fermt3, ACTB, Talin, αIIbß3, Fga, Fgb, Fgg, FXIIIb, Kng and PLC-ß were identified as the target DEPs) are considered as the key factors related to hemostatic efficacy of ZRC. Thus, integrated network pharmacology and quantitative proteomics technology were applied for the effective illuminating the molecular mechanisms of Chinese material medica.

LC-MS based plasma metabolomics study of the intervention effect of different polar parts of Hawthorn on hyperlipidemia rats.

Hawthorn, a well-known traditional Chinese medicine is used for the treatment of dyspepsia syndrome, cardiovascular disease, and hyperlipidemia. Hawthorn has complex composition. However, the effective fraction and mechanisms of action in alleviating hyperlipidemia are unknown. Therefore, the aim of this study was to evaluate the effects of four different polar components of hawthorn on hyperlipidemia rats, and to explore underlying mechanisms of action through liquid chromatography-mass spectrometry based plasma metabolomics. Hyperlipidemia rat model was established by feeding rats using a high-fat diet. High-fat model rats were then treated with four polar components of hawthorn for 14 consecutive days. Plasma samples were collected and subjected to biochemical and metabolomics analysis. Biochemical analysis showed that hawthorn n-butanol and ethyl acetate extracts had the highest efficacy on hyperlipidemia rats. Water fraction showed a partial effect, whereas petroleum ether extract was not effective against hyperlipidemia rats. Furthermore, liquid chromatography-mass spectrometry metabolomics analysis showed that the most effective fraction of hawthorn reversed the metabolic disorder in plasma of hyperlipidemia rats. Metabolomics analysis showed that hawthorn exerts its activity by modulating lipid metabolism, energy metabolism, oxidative stress, and amino acid metabolism.

Rapid quantitative detection of the discrepant compounds in differently processed Curcumae Rhizoma products by FT-NIR combined with VCPA-GA technology.

Curcumae Rhizoma (CR) and vinegar processed Curcumae Rhizoma (PCR) are common medicinal materials widely used in clinical practice in China. There are sliced CR (SCR) and two kinds of PCR products which are processed by different methods: WPCR-prepared with the whole CR root boiled in vinegar and then sliced, and SPCR-prepared with the whole CR root steamed and sliced before boiled with vinegar. In this study, the feasibility of Fourier transform near infrared spectrum (FT-NIR) used to determine the main discrepant components of SCR, WPCR and SPCR were investigated. High performance liquid chromatography (HPLC) was used to identified five discrepant compounds in the three kinds of CR products-curzerene, curcumenol, curdione, furanodienone and demethoxycurin. Pretreatment of NIR qualitative data by different methods revealed that the second derivative in combination with 9 points of Savitzky-Golay smooth (2D9S) could accurately distinguish SCR, SPCR and WPCR from each other, and the discrimination ability was improved significantly by wavebands selection. Then a model with great accuracy was established by combining with wavebands selection and partial least squares regression (PLSR). Compared with the competitive adaptive reweighted sampling (CARS) selection method, 2D9S- variable combination population analysis (VCPA)-Genetic algorithm (GA)-PLSR model was evidently more accurate in prediction of the content of curzerene, curcumenol, curdione and furanodienone, with an R2p of 0.9558, 0.9129, 0.9098 and 0.9350, as well as a ratio of performance to deviation (RPD) of 4.8454, 3.4640, 3.3020 and 4.0082, respectively. Whereas, the content of demethoxycurin failed to be well predicted. The correlation analysis revealed that the results of wavebands selection were consistent with the trend of changes in the content of these target compounds and the findings of NIR absorption analysis, and the characteristic chemical bonds of these compounds corresponded to the areas with significant correlation in the heat map. It can be concluded that the NIR system, combined with appropriate variable selection and linear regression method, can precisely distinguish SCR, SPCR and WPCR from each other, and can accurately and rapidly determine the four discrepant compounds in the three CR products, suggesting a potential of being routinely used for a more diversified analysis in medicinal herbs study.

Fishing antitumor ingredients by G-quadruplex affinity from herbal extract on a three-phase-laminar-flow microfluidic chip.

A new method for fishing antitumor ingredients by G-quadruplex recognition from Macleaya cordata seeds extracts was established using a three-phase-laminar-flow-chip (TPL chip). The TPL chip integrated the separation of drugs from the complex ingredients and organic solvent extraction, simplifying pretreatment processes and reducing reagents and time. In addition, the chip method showed a lower false negative result, owing to the gentle membrane-free filtration process based on diffusion separation in microchannel. Four ligands with high content in alkaloids of Macleaya cordata seeds were selected, those are chelerythrine (CHE), sanguinarine (SAN), protopine (PRO), and allocryptopine (ALL), which demonstrated affinity with G-quadruplex and were potential for antitumor.

[Identification of curcumin content in raw and vinegar-processed rhizomes of Curcuma kwangsiensis based on electronic nose combined with back propagation neural network].

This study aimed to establish a rapid and accurate method for identification of raw and vinegar-processed rhizomes of Curcuma kwangsiensis, in order to predict the content of curcumin compounds for scientific evaluation. A complete set of bionics recognition mode was adopted. The digital odor signal of raw and vinegar-processed rhizomes of Curcuma kwangsiensis were obtained by e-nose, and analyzed by back propagation(BP) neural network algorithm, with the accuracy, the sensitivity and specificity in discriminant model, correlation coefficient as well as the mean square error in regression model as the evaluation indexes. The experimental results showed that the three indexes of the e-nose signal discrimination model established by the neural network algorithm were 100% in training set, correction set and prediction set, which were obviously better than the traditional decision tree, naive bayes, support vector machine, K nearest neighbor and boost classification, and could accurately differentiate the raw and vinegar products. Correlation coefficient and mean square error of the regression model in prediction set were 0.974 8 and 0.117 5 respectively, and could well predict curcumin compounds content in Curcuma kwangsiensis, and demonstrate the superiority of the simulation biometrics model in the analysis of traditional Chinese medicine. By BP neural network algorithm, e-nose odor fingerprint could quickly, conveniently and accurately realize the discrimination and regression, which suggested that more bionics information acquisition and identification patterns could be combined in the field of traditional Chinese medicine, so as to provide ideas and methods for the rapid evaluation and stan-dardization of the quality of traditional Chinese medicine.

Nine absorbed components pharmacokinetic of raw and processed Moutan Cortex in normal and blood-heat and hemorrhage syndrome model rats.

Raw Moutan Cortex (RMC) and Processed Moutan Cortex (PMC) have a long history of use in China and other Asian countries. In this study, a rapid and accurate ultra-high-pressure liquid chromatography coupled with diode array detector (UHPLC-DAD) method was developed and validated for the simultaneous determination of nine absorbed compounds of RMC/PMC. After extraction by protein precipitation with methanol from plasma, the analytes were separated on an Acquity UPLC® BEH Shield RP18 column (2.1 × 100 mm, 1.7 µm, Waters, USA). Acetonitrile (A) and 0.1% (v/v) formic acid in water (B) were selected as the mobile phase to perform gradient elution. The linearity of nine analytes was >0.9915. The intra- and inter-assay precision (RSD) values were within 11.18%, and accuracy ranged from 91.32 to 101.29%. Suitable stability, matrix effect and extraction recoveries were also obtained. The validated method was applied to compare the pharmacokinetics of RMC and PMC in Blood-Heat and Hemorrhage Syndrome Model and normal rats. The results revealed that processing and the pathological state could influence the pharmacokinetic characteristics of compounds in RMC/PMC. The study willbe useful for further studies on pharmacokinetics and clinical application of raw and processed Moutan Cortex.

A mid-level data fusion approach for evaluating the internal and external changes determined by FT-NIR, electronic nose and colorimeter in Curcumae Rhizoma processing.

The aim of this study was to establish a robust and rapid method for identification of the changes of Curcumae Rhizoma (CR) in its physical properties and the components after processing. Color and odor used as the indexes for physical property evaluation in this study were quantified by non-targeted bionic detectors colorimeter and e-nose according to Chinese pharmacopoeia, and all chemical changes of the samples were observed by NIR. The technique of mid-level data fusion was adopted to simulate the recognition mode of human, and the prediction accuracy was 100%. A modified NIR band extraction method was used for feature selection after removing the redundant data which otherwise may compromise the accuracy of analysis, with a result showing bisdemethoxycurcumin and curcumol as the key factors most correlated with the changes during processing. The fused matrix was analyzed to evaluate the weight of different sensors and precisely describe the external changes of the samples, followed by a pairwise correlation analysis to investigate the role of colorimeter, e-nose and NIR in identifying the changes caused by processing as well as their correlation with each other. The results of data fusion revealed that aromatic derivatives produced during processing were closely associated with the changes in external characteristics, i.e., color and smell of the samples, while the changes in proteins did not cause significant differences. Correlation analysis demonstrated that bionic sensors could be classified into two groups: a*, WW and WS sensors, which were related to NIR band at about 6500-6700 cm-1 formed by NH vibration of amide and protein degradation, were sensitive to the processed CR; while L*, b* and WC sensors were found to be correlated to NIR band around 8000 cm-1 which was caused by first overtone of C-H combination of aromatic derivatives, thus could be employed as the detectors for raw CR.

[Herbalogical study of Colla Corii Asini(Ejiao)].

Colla Corii Asini(Ejiao)is an important Chinese medicine used in China for thousands of years, and is well known for its famous tonic properties. The herbalogical study was detailed carried out based on the naming, habitat, harvesting, processing, medicinal properties and clinical efficacy. The results showed that the name of Ejiao could be traced back to Shennong's Materia Medica, and various names of Lvpi Jiao, Penfu Jiao and Fuzhi Jiao were recorded in other ancient books. In the many intervening centuries, the main materials of Ejiao had been replaced from cow leather before Tang Dynasty to donkey skin in the middle to late Tang Dynasty. This phenomenon could be probably caused by complicated social factors of various periods and different efficacy of Ejiao made by all kinds of raw materials. Ejiao was merely processed with the simple methods before Tang Dynasty, which subsequently improved avariety of methods to enhance the supplementation action. Most importantly, Ejiao has a wide clinic application along with the development of processing theories and methods, which can be found in various Classics, especially in imperial medical case record in Qing Dynasty.

Pharmacokinetic-pharmacodynamic modeling for Moutan Cortex/Moutan Cortex charcoal and the contributions of the chemical component using support vector regression with particle swarm optimization.

Moutan Cortex (MC) and Moutan Cortex charcoal (MCC) are two kinds of Chinese medicinal materials widely used in traditional Chinese medicine (TCM) with opposite drug efficacy. And the contributions of the chemical component to the drug efficacy are still not clear. In our study, a support vector regression (SVR) model with particle swarm optimization (PSO) has been developed for simultaneously characterizing the pharmacokinetics (PK) and pharmacodynamics (PD) of MC/MCC. Then the contributions of the chemical component to the drug efficacy of MC/MCC are calculated by the weight analysis of SVR. The experimental results show that the effective substances found by the PSO-SVR model in MC and MCC are consistent with TCM theory. And the PSO-SVR model is a better model for PK-PD compared with the back-propagation neural network (BPNN). In conclusion, the PSO-SVR is a valuable tool that linked PK and PD profiles of MC/MCC with multiple components and identified the contributions of multiple therapeutic materials to the drug efficacy.