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Bi X.,Nanjing University | Bi X.,Jiangsu Engineering Research Center for Efficient Delivery System of | Bi X.,Nanjing Engineering Research Center for Industrialization of Chinese Medicine Pellets | Gong M.,Nanjing University | And 3 more authors.
Evidence-based Complementary and Alternative Medicine | Year: 2014

Shaoyao Gancao Decoction (SGD) derived from Zhang Zhongjing's "Typhoid Theory" is composed of peony and licorice, having the efficacy of nourishing liver, relaxing spasm, and relieving pain. Modern compatibility studies of SGD on chemistry, pharmacology, and pharmacokinetics all demonstrate the reasonable compatibility of peony and licorice. However, the present research on pharmacokinetics is only descriptive and limited to the influence on in vivo dynamic process of certain ingredients; correspondingly, there is lack of studies on the essence of these efficacious substances' in vivo changes; that is, whether it is because there exists in vivo drug interaction in absorption, distribution, metabolism, and excretion (ADME) of active ingredients that leads to the improvement of bioavailability. We herein take SGD as an example and suggest that it is necessary to study in vivo drug interaction of main efficacious components mediated by metabolic enzymes, transport proteins, or plasma protein binding in the course of ADME, which is helpful to illustrate the principle of pharmacokinetic compatibility from the essence leading to the changes of effective substances in vivo. © 2014 Xiaolin Bi et al. Source


Zhou W.,Nanjing University | Zhou W.,Jiangsu Engineering Research Center for Efficient Delivery System of | Zhou W.,Nanjing Engineering Research Center for Industrialization of Chinese Medicine Pellets | Shan J.,Nanjing University | And 5 more authors.
Food and Function | Year: 2015

The oral bioavailabilities of phenolic acids in Flos Lonicerae Japonicae beverage were low. The observation from an in vitro Caco-2 cell model showed that the absorptions of phenolic acids were mainly permeated via paracellular diffusion, and influenced by P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). Besides, the Papp (AP→BL) values in Flos Lonicerae Japonicae were significantly higher than those of monomers, which was attributed to the decrease of efflux ratios (<1.0) influenced by flavones (luteoloside and luteolin) on the P-gp, but they were still poorly absorbed. The results indicated that the absorptions in Flos Lonicerae Japonicae as well as those of monomers were mainly restricted by the tight junctions (TJs). Food supplements (honey and propolis) or edible excipient (chitooligosaccharide) as TJ enhancers will be investigated to improve the functions of Flos Lonicerae Japonicae healthy beverages. © 2015 Royal Society of Chemistry. Source


Zhou W.,Nanjing University | Zhou W.,Jiangsu Engineering Research Center for Efficient Delivery System of | Zhou W.,Nanjing Engineering Research Center for Industrialization of Chinese Medicine Pellets | Wang H.,Nanjing University | And 7 more authors.
PLoS ONE | Year: 2013

The current study aims to investigate the effect of chitosan derivatives on the intestinal absorption and bioavailabilities of forsythoside A (FTA) and Chlorogenic acid (CHA), the major active components in Flos Lonicerae - Fructus Forsythiae herb couple. Biopharmaceutics and pharmacokinetics properties of the two compounds have been characterized in vitro, in situ as well as in rats. Based on the identified biopharmaceutics characteristics of the two compounds, the effect of chitosan derivatives as an absorption enhancer on the intestinal absorption and pharmacokinetics of FTA and CHA in pure compound form as well as extract form were investigated in vitro, in situ and in vivo. Both FTA and CHA demonstrated very limited intestinal permeabilities, leading to oral bioavailabilities being only 0.50% and 0.13% in rats, respectively. Results from both in vitro, in situ as well as in vivo studies consistently indicated that Chito-oligosaccharide (COS) at dosage of 25 mg/kg could enhance intestinal permeabilities significantly as well as the in vivo bioavailabilities of both FTA and CHA than CMCs in Flos Lonicerae - Fructus Forsythiae herb couple preparations, and was safe for gastrointestine from morphological observation. Besides, treatment with Flos Lonicerae - Fructus Forsythiae herb couple preparations with COS at the dosage of 25 mg/kg prevented MDCK damage after influenza virus propagation, which was significantly better than control. The current findings not only identified the usefulness of COS for the improved delivery of Flos Lonicerae - Fructus Forsythiae preparations but also demonstrated the importance of biopharmaceutical characterization in the dosage form development of traditional Chinese medicine. © 2013 Zhou et al. Source


Zhou W.,Nanjing University | Zhou W.,Jiangsu Engineering Research Center for Efficient Delivery System of | Zhou W.,Nanjing Engineering Research Center for Industrialization of Chinese Medicine Pellets | Shan J.,Nanjing University | And 7 more authors.
Analytical Methods | Year: 2015

In this study, we developed a method using UPLC-ESI-MS/MS to simultaneously determine the contents of forsythoside B, loganin, macranthoidin B, dipsacoside B, rutin, arctiin, phillyrin, pinoresinol-β-d-glucoside, 3,5-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, isoquercitrin, hyperoside, astragalin, luteoloside, genistin, arctigenin, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, quercetin, luteolin, genistein, quinic acid, caffeic acid, isoforsythoside and forsythoside A in Flos Lonicerae japonicae-Fructus Forsythiae herb couple with a run time of only 8 min. The separation was performed on an Acquity UPLC HSS T3 C18 column (100 mm × 2.1 mm, 1.8 μm) at a flow rate of 0.4 mL min-1, and acetonitrile/methanol (4:1, v/v)-0.4% formic acid was used as the mobile phase. Variations in the intra- and inter-day precision of all analytes were below 5.00%; the matrix effect of all the analytes was found to be within the acceptable range; and the accuracy was evaluated by a recovery test within the range of 95.63-103.10%. The method successfully quantified the twenty-six compounds in the Flos Lonicerae japonicae-Fructus Forsythiae herb couple. Moreover, it transpired through hierarchical cluster analysis and principal component analysis that the consistency of the Flos Lonicerae japonicae-Fructus Forsythiae herb couple as the two important herbs in Flos Lonicerae japonicae-Fructus Forsythiae herb couple preparations (Shuang-Huang-Lian oral liquid, Yin-Qiao-Jie-Du tablet and Fufang Qin-Lan oral liquid), except that in Qin-Re-Jie-Du oral liquid was relatively good. The results showed that the method was accurate, sensitive and reliable. © 2015 The Royal Society of Chemistry. Source


Zhou W.,Nanjing University | Zhou W.,Jiangsu Engineering Research Center for Efficient Delivery System of | Zhou W.,Nanjing Engineering Research Center for Industrialization of Chinese Medicine Pellets | Liu S.,Nanjing University | And 7 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2013

The current study aims to investigate the pharmacokinetic study of five phenolic acids (neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, 3,5-dicaffeoylquinic acid and 3,4-dicaffeoylquinic acid) following oral administration of Flos Lonicerae preparations in rats. A rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to simultaneously determine the five phenolic acids in rat plasma. After mixing with the internal standard (IS) tinidazole, plasma samples were pretreated by liquid-liquid extraction with ethyl acetate/n-hexane (9:1, v/v). The separation was performed on an Acquity UPLC BEH C18 column (100mm×2.1mm, 1.7μm) at a flow rate of 0.4mlmin-1, and acetonitrile/methanol (4:1, v/v)-0.4% formic acid was used as mobile phase. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) via electrospray ionization (ESI) source with positive ionization mode. All calibration curves had good linearity (r>0.991) over the concentration ranges of 0.74-378ngml-1 for neochlorogenic acid, 0.50-1030ngml-1 for chlorogenic acid, 1.9-250ngml-1 for cryptochlorogenic acid, 0.74-380ngml-1 for 3,5-dicaffeoylquinic acid, and 5.1-328ngml-1 for 3,4-dicaffeoylquinic acid. The intra-and inter-day precision were within 15% and the accuracy ranged from 86.2% to 114.1%. © 2013 Elsevier B.V. Source

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