The incompatibility of traditional Chinese medicines is related to the clinical medication safety, so has attracted wide attentions from the public. With the deepening of studies on the incompatibility of traditional Chinese medicines represented by 18 incompatible herbs, the incompatibility of theory traditional Chinese medicines has raised to new heights. From the origin of incompatibility theory of traditional Chinese medicines, relationship of herbs, harms of incompatible herbs and principle of prevention to toxic effects of specific incompatible medicines, the innovation and development of the traditional Chinese medicine incompatibility theory was explored. Structurally, the incompatibility of traditional Chinese medicines refers to the opposition of two herbs based on seven emotions and clinical experience. The combination of incompatible herbs may lead to human harms, especially latent harm and inefficacy of intervention medicines. The avoidance of the combination of incompatible herbs and the consideration of both symptoms and drug efficacy are the basic method to prevent adverse reactions. The recent studies have revealed five characteristics of incompatible herbs. Toxicity potentiation, toxication, efficacy reduction and inefficacy are the four manifestations of the incompatible relations. The material changes can reflect the effects of toxicity potentiation and toxication of opposite herbs. The accumulation of toxicity and metabolic changes are the basis for latent harms. The antagonistic effect of main efficacies and the coexistence of positive and negative effects are the distinctive part of the incompatibility. The connotation of incompatible herbs plays an important role in the innovation of the traditional Chinese medicine incompatibility theory.
Drug Incompatibility ; Drug Therapy ; history ; Drugs, Chinese Herbal ; chemistry ; history ; pharmacology ; History, Ancient ; Humans ; Medicine in Literature ; Medicine, Chinese Traditional

To analyze naringin, naringenin and its metabolites in rat urine and feces after intragastric administration of alcohol extract of Exocarpium Citri Grandis, healthy SD rats were fed with alcohol extract of Exocarpium Citri Grandis for 3 days. On the last day, 0-24 h feces and 0-4 h, 4-8 h, 8-24 h urine were collected and analyzed by UPLC-Q-TOF/MS. The post-acquisition data were processed using Metabolynx The result is that naringin and its 6 metabolites, naringenin and its 4 metabolites were detected in the urine of rat. Meanwhile, naringin and its 3 metabolites, naringenin and its 2 metabolites were detected in the feces of rat.
Administration, Oral ; Animals ; Chromatography, High Pressure Liquid ; Citrus ; chemistry ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacokinetics ; Feces ; chemistry ; Flavanones ; metabolism ; urine ; Male ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

AIMTo identify the main metabolites of aconitine in the urine of rabbits.

METHODSAfter oral administration of aconitine (5 mg.kg-1), the urine of male rabbits was collected and extracted by solid phase extraction and analyzed by liquid chromatography-ion trap mass spectrometry.

RESULTSAconitine and 4 metabolites were found in the rabbit urine. Their protonated molecular ions at m/z 632, m/z 604, m/z 590, m/z 500 and multistage fragment ions with neutral loss of 60 u, 32 u, 28 u and 18 u were monitored. Their relative concentration were M1 > Aconitine > M4 > M2 > M3.

CONCLUSIONThe metabolites M1-M4 were deduced as 16-O-demethylaconitine, benzoylaconine, 16-O-demethylbenzoylaconine and aconine, respectively.

Aconitine ; analogs & derivatives ; metabolism ; urine ; Alkaloids ; urine ; Animals ; Chromatography, High Pressure Liquid ; Male ; Rabbits ; Spectrometry, Mass, Electrospray Ionization

The aim of this research was to understand the influence of rhG-CSF on the sphingosine kinase (SphK) activity of monocytes. The peripheral blood monocytes were collected from 6 peripheral blood progenitor cell donors on the fifth day of mobilization with rhG-CSF and from 5 blood donors' buffy coats. The mRNA expressions of monocyte G-CSF receptor and SphK were tested with RT-PCR. The changes of SphK activity of monocytes were assayed after being treated with rhG-CSF. The results showed that the two kinds monocytes collected from both blood donors and peripheral blood progenitor cell donors mobilized with rhG-CSF expressed mRNA of G-CSF receptor and SphK. The SphK activity of monocytes collected from blood donors was not changed significantly after being treated with rhG-CSF (P > 0.05). The SphK activity of monocytes collected from peripheral blood progenitor cell donors transiently increased by (39.6 - 87.2)% after being treated by means of rhG-CSF (P < 0.05) without obviously dose-dependent effect. It is concluded that the SphK activity of monocytes collected from peripheral blood progenitor cell donors can be activated by rhG-CSF.
Granulocyte Colony-Stimulating Factor ; pharmacology ; Hematopoietic Stem Cell Mobilization ; Humans ; Monocytes ; cytology ; enzymology ; Phosphotransferases (Alcohol Group Acceptor) ; drug effects ; metabolism ; Receptors, Granulocyte Colony-Stimulating Factor ; biosynthesis ; genetics ; Recombinant Proteins

Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disease of transformed hematopoietic progenitor cells. In order to investigate the role of sphingosine kinase-1 (SphK-1)/sphingosine 1-phosphate (S1P) signal pathway in the expression of CML cells, and to explore whether P210(bcr/abl) involved is activating SphK-1/S1P signal pathwey, the expressions of SphK-1 and S1P receptor mRNA in bcr/abl positive K562 cells and bcr/abl positive primary CML cells were detected by RT-PCR, the imatinib mesylate, the specific inhibitor of P210(bcr/abl) was employed to inhibit the P210(bcr/abl) tyrosine kinases of K562 cells and CML primary cells, and then the intracellular SphK-1 activity was assayed. The results indicated that after being cultured with 2.5 micromol/L imatinib mesylate for 0.5, 2, 6, 24 and 48 hours, the intensions of inhibiting SphK-1 activity were 0.007%, 38.9%, 34.6%, 28.1% and 76.1% resepectively. SphK-1 activity in CML cells also was reduced by 2.5 micromol/L imatinib mesylate (16.8% - 41.9% decrease). It is concluded that the CML cells express SphK-1 and different S1P receptor, and P210(bcr/abl) fusion protein in CML cells can activate SphK-1.
Benzamides ; Fusion Proteins, bcr-abl ; genetics ; metabolism ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; metabolism ; Lysophospholipids ; genetics ; metabolism ; Phosphotransferases (Alcohol Group Acceptor) ; genetics ; metabolism ; Piperazines ; pharmacology ; Pyrimidines ; pharmacology ; RNA, Messenger ; genetics ; metabolism ; Signal Transduction ; genetics ; Sphingosine ; analogs & derivatives ; genetics ; metabolism

A liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method was developed for the determination of budesonide in dog plasma. Budesonide and the internal standard triamcinolone acetonide were separated from plasma by alkalinized liquid-liquid extraction with ethyl acetate. Chromatographic separation was performed on a Capcell Pak C18 MG column with the mobile phase consisted of acetonitrile -5 mmol x L(-1) ammonium acetate (60:40, v/v) at a flow-rate of 0.50 mL x min(-1). A tandem mass spectrometer equipped with electrospray ionization source was used as detector and operated in the negative ion mode. Quantification was performed using multiple reaction monitoring (MRM) of the transitions m/z 489 --> m/z 357 and m/z 493 --> m/z 413 for budesonide and the internal standard, respectively. The linear calibration curves were obtained in the concentration range of 25.0-2000 pg x mL(-1). The lower limit of quantification was 25.0 pg x mL(-1). The intra- and inter-day relative standard deviation over the entire concentration range was less than 15%. The accuracy was in the range of -8.1% to -1.7% in terms of relative error. The method was applied to a pharmacokinetic study of budesonide controlled-release capsules in Beagle dogs. Maximal budesonide plasma level was observed after (3.5 +/- 3.3) h and the Cmax was (786 +/- 498) pg x mL(-1) after a single oral administration of 9 mg budesonide capsules, Cmax was increased to (2142 +/- 1515) pg x mL(-1) after multiple oral administration (9 mg x 5 d) of budesonide capsules. This method was selective and rapid, and the sensitivity was sufficient for the purpose of the pharmacokinetic study of budesonide controlled-release formulation.
Animals ; Anti-Inflammatory Agents ; blood ; pharmacokinetics ; Area Under Curve ; Budesonide ; blood ; pharmacokinetics ; Chromatography, Liquid ; methods ; Delayed-Action Preparations ; Dogs ; Male ; Sensitivity and Specificity ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry ; methods

The study was to understand the impact on the proliferation and cytotoxicity of donor's T cells during mobilization with rhG-CSF. The peripheral blood mononuclear cells (PBMNC) were collected from 15 donors before mobilization and on fifth day of mobilization with rhG-CSF. After the PBMNC were activated with 500 ng/ml of CD3 monoclonal antibody and 500 microg/ml of rhIL-2 for 96 hours, the activated T cells were collected for testing proliferation, cytotoxicity, Fas expression, perforin and Fas ligand (FasL) mRNA expression, the IFN-gamma concentration in the culture medium of the activated T cells was determined by radioimmunoassay. The results showed that the proliferation activity of T lymphocytes and the cytotoxicity of T cells activated with CD3 monoclonal antibody and rhIL-2 were reduced markedly after mobilization with rhG-CSF (P < 0.05). The Fas molecule expression in the activated T cells was very high both before and after mobilization with rhG-CSF (P > 0.10). The activated T cells expressed perforin mRNA and didn't express FasL mRNA both before and after mobilization with rhG-CSF. The concentration of IFN-gamma in the culture medium of the activated T cells decreased significantly after mobilization with rhG-CSF (P < 0.01). It is concluded that activity of proliferation and cytotoxicity of donor's T cells is impaired after mobilization with rhG-CSF.
Adolescent ; Adult ; Cell Proliferation ; drug effects ; Cells, Cultured ; Fas Ligand Protein ; biosynthesis ; genetics ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor ; administration & dosage ; pharmacology ; Hematopoietic Stem Cell Mobilization ; methods ; Humans ; Male ; Middle Aged ; RNA, Messenger ; biosynthesis ; genetics ; Recombinant Proteins ; T-Lymphocytes ; cytology ; drug effects ; T-Lymphocytes, Cytotoxic ; drug effects ; immunology ; fas Receptor ; biosynthesis ; genetics

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

To explore the mechanism of the absorption of flavonoids from Abelmoschus manihot flowers, in situ intestinal recirculation was performed to study the effect of the absorption at different concentrations and different intestinal regions. To evaluate the conditions of the absorption of six flavonoids from Abelmoschus manihot flowers, the concentrations of Abelmoschus manihot in the perfusion solution were determined by HPLC at predesigned time. And we have investigated the inhibitory effect of six flavonoids from Abelmoschus manihot flowers on P-glycoprotein (P-gp) drug efflux pump. The results demonstrated that the absorption rates of flavonoids from Abelmoschus manihot flowers are not significantly different (P > 0.05) at various drug concentrations, the absorption of flavonoids from Abelmoschus manihot flowers is a first-order process with the passive diffusion mechanism. The absorption rates of each of flavonoids are significantly different. The absorption rate of flavonoid glycoside was lower than that of aglycone; the flavonoids from Abelmoschus manihot flowers could be absorbed in all of the intestinal segments. The best parts of intestine to absorb hyperoside and myricetin are jejunum and duodenum, separately. Verapamil could enhance the absorption of isoquercitrin, hyperoside, myricetin and quercetin-3'-O-glucoside by inhibiting P-glycoprotein (P-gp) drug efflux pump.
ATP Binding Cassette Transporter, Sub-Family B ; antagonists & inhibitors ; Abelmoschus ; chemistry ; Animals ; Flavonoids ; administration & dosage ; isolation & purification ; pharmacokinetics ; Flowers ; chemistry ; Intestinal Absorption ; drug effects ; Male ; Perfusion ; Plant Extracts ; chemistry ; Plants, Medicinal ; chemistry ; Quercetin ; administration & dosage ; analogs & derivatives ; isolation & purification ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Verapamil ; pharmacology

OBJECTIVETo study the isolation of human bone marrow mesenchymal stem cells (MSCs) and in vitro differentiation into chondrocytes as potential seed cell for condyle cartilage tissue engineering.

METHODSHuman MSCs were isolated by percoll solution from normal human bone marrow sample and cultured in flasks. Specific cell surface markers were identified by flow-cytometry. After the cells were treated with inductive medium containing insulin, transferrin, pyruvate, dexathemesone and TGF-beta for 7 - 14 days, microscopic, histological and immuno-histo-chemical studies were performed for chondrogenic phenotype identification.

RESULTSPrimary cultures of human MSCs express CD29 and CD44 positively and meanly, but CD34, CD45 and HLA-DR negatively. After 14 days of induction, the cells were positively stained by safranin O. Immunohistochemical analysis proved strong type II collagen expression.

CONCLUSIONSPercoll helps to generate a better isolation of MSCs from human bone marrow aspirates with a purity more above 95%. The isolated MSCs can be expanded and induced in vitro to differentiate into chondrocytes by inductive medium.

Bone Marrow Cells ; cytology ; Cartilage, Articular ; chemistry ; cytology ; Cell Culture Techniques ; methods ; Cell Differentiation ; drug effects ; Cells, Cultured ; Chondrocytes ; chemistry ; cytology ; Collagen Type II ; analysis ; Dexamethasone ; pharmacology ; Humans ; Immunohistochemistry ; Insulin ; pharmacology ; Mesoderm ; cytology ; Pyruvates ; pharmacology ; Stem Cells ; cytology ; Tissue Engineering ; methods ; Transferrin ; pharmacology ; Transforming Growth Factor beta ; pharmacology