benzofurans and peoniflorin

The objectives of the present investigation were to: (1) elucidate the transport mechanism of paeoniflorin (PF) across MDCK-MDR1 monolayers; and (2) evaluate the effect of ligustilide (LIG), senkyunolide I (SENI) and senkyunolide A (SENA) on the transport of PF through blood-brain barrier so as to explore the enhancement mechanism. Transport studies of PF were performed in both directions, from apical to basolateral side (A→B) and from basolateral to apical sides (B→A). Drug concentrations were analyzed by LC-MS/MS. PF showed relatively poor absorption in MDCK-MDR1 cells, apparent permeability coefficients (Papp) ranging from 0.587 × 10(-6) to 0.705 × 10(-6) cm/s. In vitro experiments showed that the transport of PF in both directions was concentration dependent and not saturable. The B→A/A→B permeability ER of PF was more than 2 in the MDCK-MDR1 cells, which indicated that the transport mechanism of PF might be passive diffusion as the dominating process with the active transportation mediated mechanism involved. The increased Papp of PF in A→B direction by EDTA-Na₂ suggested that PF was absorbed via the paracellular route. The P-gp inhibitor verapamil could significantly increase the transport of PF in A→B direction, and ER decreased from 2.210 to 0.690, which indicated that PF was P-gp substance. The transport of PF in A→B direction significantly increased when co-administrated with increasing concentrations of LIG, SENI and SENA. An increased cellular accumulation of Rho 123 and Western blot analysis indicated that LIG, SENI and SENA had increased the transport of PF in the BBB models attribute to down-regulate P-gp expression. A decrease in transepithelial electrical resistance (TEER) during the permeation experiment can be explained by the modulation and opening of the tight junctions caused by the permeation enhancer LIG, SENI and SENA.

Topics: 4-Butyrolactone; Animals; ATP Binding Cassette Transporter, Subfamily B; Benzofurans; Biological Transport; Blood-Brain Barrier; Dogs; Dose-Response Relationship, Drug; Gene Expression Regulation; Glucosides; Humans; In Vitro Techniques; Madin Darby Canine Kidney Cells; Molecular Structure; Monoterpenes

Sulfur fumigation may induce the decrease or the chemical transformation of some active ingredients of traditional Chinese medicines in vitro. Whether sulfur fumigation can cause the pharmacokinetic changes of the active ingredients in vivo is related to the efficacy and the safety of Chinese medicines' application clinically. A sensitive, specific, and accurate method for the simultaneous determination of paeoniflorin, ferulic acid, senkyunolide A, and senkyunolide I in rat plasma by ultra high performance liquid chromatography coupled with triple quadrupole mass spectrometry was developed to evaluate the influence of sulfur fumigation to Si Wu Tang for the first time. Each compound was extracted from plasma samples by liquid-liquid extraction with ethyl acetate, and the chromatographic separation was accomplished on an Agilent Extend C18 column with a linear gradient elution. The mass spectrometric detection and analysis were performed by using an AB Sciex triple quadrupole 5500 mass spectrometer in multiple reaction monitoring mode. The validated method was successfully applied to a pharmacokinetic study of four compounds in rats after oral administration of sun-dried and sulfur-fumigated Si Wu Tang. The results provided a meaningful basis for evaluating the affection of sulfur fumigation to the clinical application and the efficacy of Si Wu Tang.

Topics: Animals; Benzofurans; Chromatography, High Pressure Liquid; Coumaric Acids; Drugs, Chinese Herbal; Fumigation; Glucosides; Male; Mass Spectrometry; Monoterpenes; Rats; Rats, Sprague-Dawley; Sulfur

In this present study, a sensitive and rapid UPLC-MS/MS method was developed for simultaneous quantification of paeoniflorin, albiflorin, ferulic acid, tetrahydropalmatine, protopine, typhaneoside and senkyunolide I in Beagle dog plasma after oral administration of the Shao-Fu-Zhu-Yu Decoction. Chloramphenicol and clarithromycin were used as internal standards. Plasma samples were processed by protein precipitation with methanol. The separation was performed on an Acquity BEH C18 column (100mm×2.1mm, 1.7μm) at a flow-rate of 0.4mL/min, using 0.1% formic acid-acetonitrile as mobile phase. Method validation was performed as per Food and Drug Administration guidelines and the results met the acceptance criteria. After validation, this method was successfully applied to a pharmacokinetic study. The results showed that the apparent plasma clearance of paeoniflorin, albiflorin, typhaneoside and senkyunolide I were significantly higher than others. Double peak was observed in plasma concentration curves of tetrahydropalmatine, the ferulic acid had a good absorption in Beagle dog plasma, and senkyunolide I was detected in plasma from the first blood sampling time (15min) and rapidly reached Tmax. The compound of typhaneoside has a low bioavailability according to the results.

Topics: Administration, Oral; Animals; Benzofurans; Benzophenanthridines; Berberine Alkaloids; Bridged-Ring Compounds; Chromatography, High Pressure Liquid; Coumaric Acids; Dogs; Drugs, Chinese Herbal; Female; Glucosides; Glycosides; Monoterpenes; Tandem Mass Spectrometry

To establish a LC-MS/MS method for determining the concentration of tanshinone IIA, salvianolic acid B and paeoniflorin of refined coronary cataplasm in rabbit plasma, in order to determine the concentration of the three main ingredients in blood after transdermal administration and calculate their pharmacokinetic parameters.. Rabbits were given refined coronary cataplasm on the basis of 15 g x kg(-1) by transdermal administration to detect the plasma concentration of the three main ingredients using LC-MS/MS. Winnonlin software was used to calculate their major pharmacokinetic parameters.. Tanshinone IIA, salvianolic acid B and paeoniflorin showed good linearity (r>0.999) at 1-100, 50-1 000, 10-1 000 microg x L(-1) respectively in plasma, with average recovery rate of 96.57%, 91.90%, 95.93%, respectively. The RSD within day were less than 15%. After transdermal administration of refined coronary cataplasm in rabbits, the main pharmacokinetic parameters of tanshinone IIA, salvianolic acid B or paeoniflorin were as follows: Cmax (20.85 +/- 12.68), (636.25 +/- 386.91), (787.80 +/- 395.64) microg x L(-1); Tmax (0.49 +/- 0.28), (0.44 +/- 0.27), (0.46 +/- 0.30) h.. The LC-MS/MS method is highly selective and sensitive to determine the concentration of samples in rabbit plasma. The pharmacokinetic characteristics of tanshinone IIA, salvianolic acid B and paeoniflorin are suitable to assess the percutaneous absorption of refined coronary cataplasm.

Topics: Abietanes; Animals; Benzoates; Benzofurans; Bridged-Ring Compounds; Chromatography, Liquid; Coronary Disease; Drugs, Chinese Herbal; Glucosides; Humans; Male; Monoterpenes; Rabbits; Tandem Mass Spectrometry

To study the dissolution rate of active components of different extracting solvents of Danggui Chishao drug pair.. The dissolution rates of phenolic acids (ferulic acid, vanillic acid and gallic acid), monoterpenes (gallic acid, peoniflorin, albiflorin, hydroxypeoniflorin and galloylpaeoniflorin) and phthalates (senkyunolide and ligustilide) contained in Danggui Chishao drug pair were determined by quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS) and ultra high performance liquid chromatography in combination with triple-quadrupole mass spectrometry (UPLC-TQ-MS).. The dissolution rates of phenolic acids and monoterpenes decreased with the increase in alcohol concentration, on the contrary the rates of phthalates increased. The relative dissolution rates of most active components were relatively high in water and low concentration alcohol than other solvents.. Liquid chromatography-mass spectrometry is practical for comprehensive multi-component assessment on traditional Chinese medicine preparation processes and can provide reference for optimization of processing parameters.

Topics: 4-Butyrolactone; Benzoates; Benzofurans; Bridged-Ring Compounds; Chromatography, Liquid; Drugs, Chinese Herbal; Gallic Acid; Glucosides; Hydroxybenzoates; Mass Spectrometry; Monoterpenes; Phthalic Acids; Solvents; Vanillic Acid

Traditional Chinese medicine (TCM) is a complex system, which consists of numerous compounds with related mechanisms to maximize therapeutic efficacy with minimal adverse effects. Some new methods disclosing the contribution of these constituents as well as their relationship in the formula are necessary for elucidating the bio-active constituents and the working mechanisms of TCM. In this study, depletion of target components using preparative HPLC followed by antiplatelet and anticoagulation activities evaluation was first applied to investigate the roles of paeoniflorin and senkyunolide I in a well-known formula, SiWu decoction. The results showed that both paeoniflorin and senkyunolide I not only directly brought about some bio-activities, but also indirectly made the contribution to the total bio-activity reflection of SiWu decoction, especially the latter should deserve to be drawn attention to the research of complicated bio-active constituents of TCM or its formula. So, the significant and effective approach will be very useful for the elucidation of the contribution of each different chemical constituent to the bio-activity of a TCM formula. Furthermore, this study demonstrated the potential utilization of preparative HPLC in the research of TCM.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Benzoates; Benzofurans; Bridged-Ring Compounds; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Glucosides; Humans; Male; Medicine, Chinese Traditional; Molecular Structure; Monoterpenes; Platelet Aggregation; Platelet Aggregation Inhibitors; Rabbits; Thrombin Time

We have used microarray technology to detect the effect of Guanxin No.2 decoction on gene expression in different areas of the myocardial infarcted heart of rats.. Male Sprague-Dawley rats (180-200 g) were randomly divided into three groups: sham-operated; coronary artery ligation; and coronary artery ligation plus administration of Guanxin No.2 decoction (10.0 g raw materials/kg per day by gavage). The experiment was carried out on day seven after ligation.. We found that the gene expression using microarray technology showed many differences in the border infarcted left ventricular area compared with the remote noninfarcted left ventricular area after administration of Guanxin No.2 decoction.. Guanxin No.2 decoction has a long history in treating ischaemic cardiomyopathy in China, but the molecular mechanism has been unclear. In this study we found that some important genes may have contributed to the cardioprotective effect of Guanxin No.2 decoction.

Topics: Animals; Benzaldehydes; Benzoates; Benzofurans; Bridged-Ring Compounds; Cardiotonic Agents; Carthamus tinctorius; Catechols; Chalcone; Coumaric Acids; Dalbergia; Drugs, Chinese Herbal; Gene Expression; Gene Expression Profiling; Glucosides; Heart Ventricles; Hydroxybenzoates; Lactates; Ligusticum; Male; Monoterpenes; Myocardial Infarction; Oligonucleotide Array Sequence Analysis; Paeonia; Plant Extracts; Quinones; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Salvia miltiorrhiza

To develop a method for the determination of salvianolic acid B and paeoniflorin in Shuangdan granules.. The chromatographic separation was performed on a Zorbax SB C18 column with a linear gradient elution of phosphoric acid-water (0.05:100) and phosphoric acid-acetonitrile-methanol (0.05:4:96) was used. The flow rate was 1 mL x min(-1) and column temperature was set at 25 degrees C. The UV detection wavelength was set at 230 nm.. The linear ranger was of 0.710-22.7 microg for salvianolic acid B and 0.103-3.30 microg for paeoniflorin. Three batches of Shuangdan granules were analyzed, and the content of salvianolic acid B ranged from 6.46-11.6 mg x g(-1) and paeoniflorin ranged from 1.44-1.78 mg x g(-1).. The method was accurate, reproducible, reliable, and could be used for quantitative control of Shuangdan granules.

Topics: Benzoates; Benzofurans; Bridged-Ring Compounds; Chromatography, High Pressure Liquid; Drug Combinations; Drugs, Chinese Herbal; Glucosides; Monoterpenes; Paeonia; Plants, Medicinal; Quality Control; Reproducibility of Results; Salvia miltiorrhiza