Data mining technology has become a powerful tool in traditional Chinese medicine (TCM) research. In this paper, based on the principle and basic requirements of data mining, the mining methods and procedures were described. And then the application of data mining technology in Chinese medicine pair research was classified and summarized, such as the compatibility characters, characteristic pairs, dosage-effect relationship and property compatibility, which provide the direction and data base for modern research of Chinese medicine pair.
Cluster Analysis ; Data Mining ; methods ; Drug Interactions ; Drug Prescriptions ; Medicine, Chinese Traditional ; methods

The combination of Danggui and Honghua (GH) is a popular herb pair commonly used in clinic for the treatment of blood stasis syndrome in China. To evaluate the activating blood circulation and dissipating blood stasis effects of the combination of different proportions of Danggui and Honghua on acute blood stasis rats, and optimize the proportion of GH to have the best activating blood circulation and dissipating blood stasis effect. Acute blood stasis rat model was induced by subcutaneous injection of adrenaline and ice water bath. The blood stasis rats were administrated intragastrically with GH (1 : 0, 4 : 1, 2 : 1, 3 : 2, 1 : 1, 2 : 3, 1: 2, 1 : 4 and 0 : 1) extracts. The whole blood viscosity (WBV), plasma viscosity (PV), and high shear whole blood relative index (HSWBRI), low shear whole blood relative index (LSWBRI), and erythrocyte aggregation index (EAI) were tested to observe the effects of GH on hemorheology of blood stasis rats. And the maximum aggregation induced by adenosine diphosphate (ADP) was tested to observe the effect of GH on platelet aggregation index of blood stasis rats. In addition, the prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT) and plasma fibrinogen (FIB) were tested to observe the effects of GH on blood coagulation function of blood stasis rats. Then principal component analysis and multi-attribute comprehensive index methods were both used to comprehensively evaluate the total activating blood circulation and dissipating blood stasis effects of GH. The results showed that the hemorheological indexes and coagulation parameters of model group both had significant differences with normal group. Compared with model group, GH (1 : 0, 4 : 1, 2: 1, 3 : 2, 1 : 1, 2 : 3, 1 : 2, 1 : 4 and 0 : 1) could improve all the blood hemorheology indexes and regulate part indexes of blood coagulation function and platelet aggregation in acute blood stasis rats. Based on principal component analysis and multi-attribute comprehensive index methods, GH 1 : 1 and GH 3 : 2 both had the best effect of blood circulation and dissipating blood stasis, and the effect of GH 1 : 1 was slightly better than GH 3 : 2. These results suggest that GH could obviously ameliorate the abnormality of hemorheology and blood coagulation function in acute blood stasis rats. The optimized proportion of GH was consistent with regulations of medicine usage that GH 1 : 1 had the highest frequency used in traditional Chinese formulae. It could provide scientific basis for more effective application of the compatibility between Danggui and Honghua in modern clinic medicine.
Animals ; Blood Coagulation ; Blood Viscosity ; Carthamus tinctorius ; China ; Drugs, Chinese Herbal ; pharmacology ; Erythrocyte Aggregation ; Hemorheology ; Partial Thromboplastin Time ; Platelet Aggregation ; Principal Component Analysis ; Prothrombin Time ; Rats ; Rats, Sprague-Dawley ; Thrombin Time

OBJECTIVETo establish a method for studying efficacious materials of traditional Chinese medicines from an overall perspective.

METHODCarthamus tinctorius was taken the example. Its major components were depleted by preparing liquid chromatography. Afterwards, the samples with major components depleted were evaluated for their antioxidant effect, so as to compare and analyze the major efficacious materials of C. tinctorius with antioxidant activity and the contributions.

RESULTSeven major components were depleted from C. tinctorius samples, and six of them were identified with MS data and control comparison. After all of the samples including depleted materials are compared and evaluated for their antioxidant effect, the findings showed that hydroxysafflor yellow A, anhydrosafflor yellow B and 6-hydroxykaempferol-3, 6-di-O-glucoside-7-O-glucuronide were the major efficacious materials.

CONCLUSIONThis study explored a novel and effective method for studying efficacious materials of traditional Chinese medicines. Through this method, we could explain the direct and indirect contributions of different components to the efficacy of traditional Chinese medicines, and make the efficacious material expression of traditional Chinese medicines clearer.

Alkalies ; chemistry ; Antioxidants ; chemistry ; Carthamus tinctorius ; chemistry ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; Glucosides ; chemistry ; Mass Spectrometry

Along with progress of modern science and technology, human is utilizing natural resources and their inherent law more effectively and more efficiently according to their own purposes. Chinese medicine pair (CMP) is relatively fixed combination of two TCMs which was proven to be effective in clinical application. CMP has its inner specification, and it is an intermediate point between single herb and many TCM formulae. With the aid of modern science and technology, and by means of choosing appropriate strategies and approaches, the compatibility rules of CMP might be revealed, which will be significant to develop the compatibility theory of TCM formulae and create modern TCM new drugs.
Animals ; Clinical Trials as Topic ; Drug Interactions ; Humans ; Medicine, Chinese Traditional ; methods ; Research Design ; Systems Biology

The combination of Angelicae sinensis Radix (Danggui, DG) and Astragali Radix (Huangqi, HQ) is a popular herb pair commonly used in clinic for the treatment of blood deficiency syndrome in China. The aim of this paper is to study the interaction of DG and HQ nourishing and tonifying blood effects by response surface method. The blood deficiency mice were induced by injecting N-acetylphenylhydrazine (sc) and cyclophosphamide (ip). The blood deficiency mice were administrated intragastrically with DG-HQ extracts (0:1, 1: 5, 2:5, 2:3, 1:1, 3:2, 5:2, 5:1, 1:0). The changes of the peripheral blood indexes and organ indexes were observed. The indexes were integrated by comprehensive index method; the interactions of DG and HQ were analyzed by the response surface diagram established with Matlab software. The results showed that DG and HQ at most of their combination ratios had synergic effect. Within the range of 1:5 - 5:1, all of the extracts of DG-HQ showed synergic effect, and among which, high-doses had better effects than low-doses. The highest value (-1) of the synergic effect was showed when DG was 10 - 40 g at the same time of HQ as 90 -180 g, and DG was 50 - 100 g at the same time of HQ as 20 - 100 g. DG-HQ at all combination dosages within Chinese Pharmacopeia (DG: 6 - 12 g, HQ: 9 - 30 g) had certain synergic effect, and Danggui Buxue Decoction (DG: 6 g, HQ: 30 g) also was at this range. The results provided scientific basis to the clinical application of DG and HQ. And the response surface method was firstly applied to quantitatively evaluate the bio-activity change of herb combination, which provided a novel way for modern basic research on the interaction of herbs.
Angelica sinensis ; chemistry ; Animals ; Astragalus membranaceus ; chemistry ; Blood Cell Count ; Drug Combinations ; Drug Interactions ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Female ; Mice ; Mice, Inbred ICR ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Random Allocation

The metabolic effect of Fo-Shou-San on blood deficiency mice was studied by using metabolomic method. UPLC-QTOF/MS was used to analyze the plasma metabolome in blood deficiency mice. MS data were processed by MarkerLynx software. With multivariate statistical analysis of plasma metabolite profiles, a clear separation among control, blood deficiency model, and Fo-Shou-San groups was achieved. Potential biomarkers were selected according to the parameters of variable importance in the projection (VIP) and identified according to MS information and database retrieval. The metabolic network of blood deficiency was predicted via MetPA database. Twenty-two potential biomarkers were identified and used to explain the thiamine metabolism, arachidonic acid metabolism, sphingolipid metabolism, glyoxylate and dicarboxylate metabolism, histidine metabolism, nicotinate and nicotinamide metabolism, cysteine and methionine metabolism, tryptophan metabolism, starch and sucrose metabolism, tyrosine metabolism and citrate cycle (TCA cycle). Those metabolic pathways were disturbed in blood deficiency mice, but which could be regulated nearly to normal state after Fo-Shou-San administration. In this study, the metabolomics of blood deficiency mice and the action mechanism of nourishing blood effect of Fo-Shou-San were evaluated. The physiological and metabolic state of the organism could be represented comprehensively by using metabolomics. And metabolomics can be used to evaluate the pharmacodynamics and related mechanisms of Chinese medicine and formulae.
Animals ; Arachidonic Acid ; metabolism ; Biomarkers ; blood ; Blood Coagulation Disorders ; blood ; metabolism ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; pharmacology ; Female ; Metabolic Networks and Pathways ; drug effects ; Metabolome ; Metabolomics ; Mice ; Mice, Inbred ICR ; Plasma ; metabolism ; Random Allocation ; Spectrometry, Mass, Electrospray Ionization ; Sphingolipids ; metabolism ; Thiamine ; metabolism

OBJECTIVETo evaluate the effect of Taohong Siwu Tang and its fractions on hotplate-induced pain in mice, acetic acid-induced writhing response, dysmenorrheal model and isolated uterine contraction in vitro in mice, and discuss material basis of effect sites.

METHODThe samples of fractions were prepared by macroporous adsorptive resins (TH-1-TH-15). In the whole animal experiment, the hotplate-induced pain mice model was established to observe the effect of the samples on pain threshold in mice; the acetic acid-induced writhing response mice model was built to observe the effect of the samples on the writhing response in mice; the mice dysmenorrheal model was established to observe the effect of the samples on the writhing response, and calcium ion (Ca2+) and nitric oxide (NO) levels in uterine tissue of mice. In the isolated uterus contraction experiment, the oxytocin-induced isolated uterus contraction mice model was established to observe the effect of the samples on the isolated uterus contraction index. HPLC-DAD method was adopted for the content determination of effect sites.

RESULTAccording to the evaluation of the integration geological effect, beside TH-2 and TH-4, other three active fractions (TH-9, TH-10 and TH-11) extracted from Taohong Siwu Tang are the main effect sites. Their chemical components were analyzed and identified as monoterpene glycosides, phthalides, organic acids, etc.

CONCLUSIONThe effect sites of Taohong Siwu Tang on dysmenorrhea are TH-9, TH-10 and TH-11, which are 30% - 50% active fractions obtained from water-soluble small-molecular fractions by gradient elution using ethanol through macroporous absorption resin. Compared with TH-10 and TH-11, TH-9 shows stronger effect, which may be related to the type and content of chemical components it contains.

Animals ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; analysis ; therapeutic use ; Dysmenorrhea ; drug therapy ; Female ; Medicine, Chinese Traditional ; Mice ; Mice, Inbred ICR

UNLABELLEDTo establish a rapid component identification method for chemical constituents contained in traditional Chinese medicines and natural products by using liquid chromatography-mass spectrometry database technology.

METHODUltra-high performance liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was applied to collect the retention time and mass spectrum data of chemical constituents contained in traditional Chinese medicines and natural products, and establish a mass spectrum database. The Identify function from Chromalynx XS module in Masslynx workstation was applied to identifiy each chromatographic peak in an automatic and rapid manner. The retention time correction method was used to correct the retention time of identical compounds in different chromatographic systems, in order to improve the adaptability of the method.

RESULTCurrently, the UPLC-MS library contains LC-MS information of more than 210 such chemical constituents as alkaloids, flavonoids, quinones, phenylpropanoids and terpenes, including retention times, xact molecular weights of quasi-molecular ion peaks and their fragment ions under positive and negative modes, respectively. The detection rate of identifying samples by suing the method was around 90%.

CONCLUSIONCompared with manual identification, the method is simple, rapid and highly accurate. The usage of the linear correction for retention times helps solve the disunity of mass spectrum databases caused by different retention times in different chromatographic systems to a certain extent, and expand the application range of the method.

Chromatography, Liquid ; methods ; Databases, Factual ; Mass Spectrometry ; methods ; Medicine, Chinese Traditional

OBJECTIVETo analyze the difference of chemical compounds of frankincense-myrrh before and after their compatibility, and evaluate the effect of differentiated compounds on NO generated by LPS-induced peritoneal macrophage cells in rats, in order to discuss synergetic material basis of frankincense-myrrh compatibility from the prospective of change in chemical constituents.

METHODUPLC-Q-TOF-MS/MS combined technology was used to analyze the chemical components of frankincense-myrrh before and after their compatibility. MarkerLynx 4. 1 statistical software was used to analyze differentiated compounds before and after their compatibility.

RESULTThe results of PCA showed that there were significant differences in the combined extracts of frankincense-myrrh and the chromatogram of their combined liquid, suggesting significant differences in their chemical compounds before and after their compatibility; after their compatibility, the dissolution of pentacyclic triterpenoid (alpha-boswellic acid, beta-boswellic acid) and tetracyclic triterpenoid (elemonic acid, 3-acetoxy-16-hydroxy-dammar-24-ene, 3-hydroxytirucalla-8,24-dien-21-oic acid or 3-hydroxytirucalla-7,24-dien-21-oic acid) increased notably, while the dissolution of both yclic sesquiterpenes and macrocyclic diterpenoids decreased. According to the evaluation on in vitro activity, 2-methoxy-8, 12-epoxy-germa-1 (10), 7, 11-triene-6-ketone, 2-methoxy-5-acetoxyl-furan-germa-1 (10)-alkene-6-ketone and 3-carbonyl Euphorbia kansui-8, 24-diene-21-carboxylic acid notably inhibited NO generated by LPS-induced peritoneal macrophage cells in rats.

CONCLUSIONThese findings provide scientific basis and reference for studies on anti-inflammatory material basis of frankincense-myrrh compatibility.

Animals ; Anti-Inflammatory Agents, Non-Steroidal ; chemistry ; isolation & purification ; Boswellia ; chemistry ; Chromatography, Liquid ; Commiphora ; chemistry ; Drug Synergism ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Lipopolysaccharides ; pharmacology ; Macrophages, Peritoneal ; drug effects ; Male ; Mice ; Mice, Inbred BALB C ; Molecular Structure ; Nitric Oxide ; metabolism ; Tandem Mass Spectrometry ; Terpenes ; chemistry ; isolation & purification ; Triterpenes ; chemistry ; isolation & purification

OBJECTIVETo study the pharmacodynamic interaction of nourishing and tonifying blood effects of the herb pair consisting of Angelica sinensis and Ligusticum chuanxiong by response surface method.

METHODSThe blood deficiency rat model was induced by injecting N-acetylphenylhydrazine and cyclophosphamide. The effects of Angelica sinensis and Ligusticum chuanxiong in different proportions (0:1, 1:5, 2:5, 2:3, 1:1, 3:2, 5:2, 5:1, and 1:0) and at different concentrations on the peripheral blood index and the organ indices were observed. Then all indices were integrated to the total nourishing effect value by comprehensive index method. The interaction was analyzed by response surface method. The model parameters were estimated with nonlinear regression. The three-dimensional response surfaces were constructed with Matlab Software.

RESULTSIn the response surface, most compatibility of Angelica sinensis and Ligusticum chuanxiong showed synergistic action, some showed addition action, and few of them showed obvious antagonist action. The proportion of Angelica sinensis and Ligusticum chuanxiong from 4:1 to 2:1 and the dose of Angelica sinensis and Ligusticum chuanxiong from low to high showed addition action, while the other proportions showed obvious addition action at low dose and synergistic action at high dose.

CONCLUSIONSThe research results could provide scientific evidence for reasonable application of Angelica sinensis and Ligusticum chuanxiong in clinics of Chinese medicine. The quantitative analysis on drug interactions of herbal compatibility by response surface method could provide reference for relative studies.

Angelica sinensis ; chemistry ; Animals ; Drug Interactions ; Drugs, Chinese Herbal ; pharmacology ; Female ; Ligusticum ; chemistry ; Mice ; Mice, Inbred ICR