Jiangsu Engineering Research Center for Efficient Delivery System of TCM

Nanjing, China

Jiangsu Engineering Research Center for Efficient Delivery System of TCM

Nanjing, China
SEARCH FILTERS
Time filter
Source Type

Du L.-N.,Nanjing University | Du L.-N.,Beijing Childrens Hospital Affiliated to Capital Medical UniversityBeijing | Xie T.,Nanjing University | Xu J.-Y.,Nanjing University | And 7 more authors.
Journal of Ethnopharmacology | Year: 2015

Abstract Ethnopharmacological relevance Jinxin oral liquid (JOL) is a traditional Chinese medicine (TCM) formula modified from ma-xing-shi-gan-tang, an ancient formula widely used in the treatment of respiratory diseases such as bronchitis, pneumonia, and asthma. In our previous studies, JOL was shown to safely and effectively treat viral pneumonia, especially that involving respiratory syncytial virus (RSV). Aim of the study To investigate the mechanism of the effect of JOL in RSV infected mice, using a metabolomics approach based on ultra-performance liquid chromatography coupled with linear ion trap quadrupole-Orbitrap mass spectrometry (UPLC/LTQ-Orbitrap-MS). Materials and methods BALB/c mice were divided into four groups, the control group (saline inoculation/no treatment), RSV group (RSV inoculation/saline treatment), RSV+JOL group (RSV inoculation/JOL treatment), and RSV+Riba group (RSV inoculation/ribavirin treatment). Plasma and lung tissue samples were collected 7 days after the inoculation/treatment protocols, and UPLC/LTQ-Orbitrap-MS method based on metabolomics was developed. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were utilized to identify biomarkers potentially associated with the anti-RSV activity of JOL. Results JOL was associated with reduced inflammatory responses in RSV-infected lung tissue. The combination of PCA and OPLS-DA revealed deviations in 11 biomarkers in plasma, and 16 biomarkers in lung tissue induced by RSV that were corrected with JOL treatment. These biomarkers were primarily components of metabolic pathways involving glycerophosphocholines, sphingolipids, and glycerolipids. JOL was able to restore the abnormal levels of these biomarkers detected in the plasma and lung tissue of RSV-infected mice to approximately normal levels. Conclusions This study suggested that JOL can treat RSV pneumonia effectively, partially by ameliorating the associated disturbances to lipid metabolism. The results provided insight into the anti-RSV mechanism of JOL, and also demonstrated that metabolomics is a valuable tool for investigating the efficacy of TCM treatment for RSV pneumonia, and the associated biomarkers involved. © 2015 Elsevier Ireland Ltd.


Zhou W.,Nanjing University | Zhou W.,Jiangsu Engineering Research Center for Efficient Delivery System of TCM | Zhou W.,Nanjing Engineering Research Center for Industrialization of Chinese Medicine Pellets | Zhu X.,Nanjing University | And 7 more authors.
Pharmacognosy Magazine | Year: 2014

Background: Forsythoside A (FTA), one of the main active ingredients in Shuang-Huang-Lian (SHL), possesses strong antibacterial, antioxidant and antiviral effects, and its pharmacological effects was higher than that of other ingredients, but the absolute bioavailability orally was approximately 0.72%, which was significantly low, influencing clinical efficacies of its oral preparations seriously. Materials and Methods: In vitro Caco-2 cell and in vivo pharmacokinetics study were simultaneously performed to investigate the effects of absorption enhancers based on tight junctions: sodium caprate and water-soluble chitosan on the intestinal absorption of FTA, and the eventual mucosal epithelial damage resulted from absorption enhancers was evaluated by MTT test and morphology observation, respectively. The pharmacological effects such as antivirus activity improvement by absorption enhancers were verified by MDCK damage inhibition rate after influenza virus propagation. Results: The observations from in vitro Caco-2 cell showed that the absorption of FTA in SHL could be improved by absorption enhancers. Meanwhile, the absorption enhancing effect of water-soluble chitosan may be almost saturable up to 0.0032% (w/v), and sodium caprate at concentrations up to 0.64 mg/mL was safe, but water-soluble chitosan at different concentrations was all safe for these cells. In pharmacokinetics study, water-soluble chitosan at dosage of 50 mg/kg improved the bioavailability of FTA in SHL to the greatest extent, and was safe for gastrointestine from morphological observation. Besides, treatment with SHL with water-soluble chitosan at dosage of 50 mg/kg prevented MDCK damage after influenza virus propagation better significantly than that of control. Conclusion: Water-soluble chitosan at dosage of 50 mg/kg might be safe and effective absorption enhancer for improving the bioavailability of FTA and the antivirus activity in vitro in SHL.


Zhou W.,Nanjing University | Zhou W.,Jiangsu Engineering Research Center for Efficient Delivery System of TCM | 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.


Zhou W.,Nanjing University | Zhou W.,Jiangsu Engineering Research Center for Efficient Delivery System of TCM | Zhou W.,Nanjing Engineering Research Center for Industrialization of Chinese Medicine Pellets | Shan J.,Nanjing University | And 9 more authors.
Phytomedicine | Year: 2014

Phenolic acids, the main active ingredients in Flos Lonicerae extract possess strong antibacterial, antioxidant and antiviral effects, and their contents was higher largely than that of other ingredients such as flavones, but the absolute bioavailability orally was significantly low, which is significant low influencing clinical efficacies of its oral preparations. In the present study, in vitro Caco-2 cell, in situ single-pass intestinal perfusion and in vivo pharmacokinetics study were performed to investigate the effects of COS on the intestinal absorption of phenolic acids. The pharmacological effects such as antiviral activity improvement by COS were verified by MDCK cell damage inhibition rate after influenza virus propagation. The observations from in vitro Caco-2 cell showed that the absorption of phenolic acids in Flos Lonicerae extract could be improved by COS. Meanwhile, COS at the same low, medium and high concentrations caused a significant, concentration-dependent increase in the Papp-value for phenolic acids compared to the control group (p < 0.05), and was all safe for the Caco-2 cells. The observations from single-pass intestinal perfusion in situ model showed that the intestinal absorption of phenolic acids can be enhanced by COS. Meanwhile, the absorption enhancing effect of phenolic acids might be saturable in different intestine sites. In pharmacokinetics study, COS at dosage of 25 mg/kg improved the bioavailability of phenolic acids in Flos Lonicerae extract to the greatest extent, and was safe for gastrointestine from morphological observation. Besides, treatment with Flos Lonicerae extract with COS at dosage of 25 mg/kg prevented MDCK cell damage upon influenza virus propagation better than that of control. All findings above suggested that COS at dosage of 25 mg/kg might be safe and effective absorption enhancer for improving the bioavailability of phenolic acids and the antiviral activity in vitro in Flos Lonicerae extract. © 2013 Elsevier GmbH.


Zhou W.,Nanjing University | Zhou W.,Jiangsu Engineering Research Center for Efficient Delivery System of TCM | Zhou W.,Nanjing Engineering Research Center for Industrialization of Chinese Medicine Pellets | Tan X.,Jiangsu Provinical Academy of Chinese Medicine | And 8 more authors.
Phytomedicine | Year: 2014

Phenylethanoid glycosides, the main active ingredients in Fructus Forsythiae extract possesses strong antibacterial, antioxidant and antiviral effects, and their contents were higher largely than that of other ingredients such as lignans and flavones, but their absolute bioavailability orally was significantly low, which influenced clinical efficacies of its oral preparations seriously. In the present study, the absorption mechanism of phenylethanoid glycosides was studied using in vitro Caco-2 cell model. And the effect of chito-oligosaccharide (COS) on the intestinal absorption of phenylethanoid glycosides in Fructus Forsythiae extract was investigated using in vitro, in situ and in vivo models. The pharmacological effects such as antiviral activity improvement by COS were verified by MDCK cell damage inhibition rate after influenza virus propagation. The observations from in vitro Caco-2 cell showed that the absorption of phenylethanoid glycosides in Fructus Forsythiae extract so with that in monomers was mainly restricted by the tight junctions, and influenced by efflux transporters (P-gp and MRP2). Meanwhile, the absorption of phenylethanoid glycosides in Fructus Forsythiae extract could be improved by COS. Besides, COS at the same low, medium and high concentrations caused a significant, concentration-dependent increase in the Papp-value for phenylethanoid glycosides compared to the control group (p < 0.05), and was all safe for the Caco-2 cells. The observations from single-pass intestinal perfusion in situ model showed that the intestinal absorption of phenylethanoid glycosides can be enhanced by COS. Meanwhile, the absorption enhancing effect of phenylethanoid glycosides might be saturable in different intestine sites. In pharmacokinetics study, COS at dosage of 25 mg/kg improved the bioavailability of phenylethanoid glycosides in Fructus Forsythiae extract to the greatest extent, and was safe for gastrointestine from morphological observation. In addition, treatment with Fructus Forsythiae extract with COS at dosage of 25 mg/kg prevented MDCK cell damage upon influenza virus propagation better than that of control. All findings above suggested that COS at dosage of 25 mg/kg might be safe and effective absorption enhancer for improving the bioavailability of phenylethanoid glycosides and the antiviral activity in vitro in Fructus Forsythiae extract. © 2014 Elsevier B.V. All rights reserved.


Zhang W.,Nanjing University | Zhang W.,Jiangsu Engineering Research Center for Efficient Delivery System of TCM | Zhang W.,Nanjing Engineering Research Center for Industrialization of Chinese Medicine Pellets | Di L.-Q.,Nanjing University | And 9 more authors.
Journal of Ethnopharmacology | Year: 2014

Ethnopharmacological relevance Glycyrrhizae uralenis (GU) is often prescribed together with Cortex daphnes (CD) in traditional Chinese medicinal practice to increase the efficacy of CD on the treatment of rheumatoid arthritis (RA), but the reasons were still unknown. In order to clarify the rationality of herbaceous compatibility between CD and GU, the comparative evaluations on pharmacokinetic behaviors of daphnetin (a predominantly active ingredient in CD) after intragastric administration of CD and CD-GU (combination of CD and GU) extract were studied. In addition, the effects of glycyrrhizin and liquiritin, active ingredients of Glycyrrhiza triterpenes and Glycyrrhiza flavones respectively, on the pharmacokinetics of daphnetin were also investigated. Materials and methods Five groups of rats were orally administered with CD extract, CD-GU extract, pure daphnetin, co-administration of daphnetin and glycyrrhizin as well as co-administration of daphnetin and liquiritin at the same single dose of daphnetin (20 mg/kg). The rat plasma concentrations of daphnetin were determined by our developed UPLC-MS/MS method. The pharmacokinetics of daphnetin in above groups were investigated and compared. Results Comparing with oral administration of CD extract, AUC and T max of daphnetin significantly increased after giving CD-GU (p<0.05). In addition, in comparison to daphnetin alone, co-administration of daphnetin with liquiritin significantly increased the AUC and Cmax of daphnetin for ~1.5-fold, while co-administered with glycyrrhizin showed limited impact on the pharmacokinetics of daphnetin. Conclusions In this study, it was found that liquiritin, one of the major components of GU, significantly enhanced the bioavailability of the main component daphnetin in CD. In addition, the bioavailability of daphnetin in the CD-GU prescription was also significantly higher than that in CD alone, which could be due to liquiritin. Such results explained the mechanism of the increased efficacy in treating RA with the combined use of CD and GU. © 2014 Elsevier Ireland Ltd.


Zhou W.,Nanjing University | Zhou W.,Jiangsu Engineering Research Center for Efficient Delivery System of TCM | 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.


Bi X.,Nanjing University | Bi X.,Jiangsu Engineering Research Center for Efficient Delivery System of TCM | 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.


Zhou W.,Nanjing University | Zhou W.,Jiangsu Engineering Research Center for Efficient Delivery System of TCM | Zhou W.,Nanjing Engineering Research Center for Industrialization of Chinese Medicine Pellets | Shan J.,Nanjing University | And 7 more authors.
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2014

The current study aims to investigate the pharmacokinetic study of eight caffeic acid derivatives (forsythoside A, isoforsythoside, forsythoside B, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, 3,5-dicaffeoylquinic acid and 3,4-dicaffeoylquinic acid) following oral administration of Flos Lonicerae-Fructus Forsythiae herb combination in rats. A rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to determine the eight caffeic acid derivatives simultaneously in rat plasma. After mixing with the internal standard (IS) tinidazole, plasma samples were pretreated by liquid-liquid extraction with n-butyl alcohol/ethyl acetate (7:3, v/v). The separation was performed on an Acquity UPLC HSS T3 C18 column (100mm×2.1mm, 1.8μm) 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 and negative ionization modes. All calibration curves had good linearity (r>0.991) over the concentration ranges of 1.097-2246ngmL-1 for neochlorogenic acid, 6.535-6692ngmL-1 for chlorogenic acid, 2.103-2153ngmL-1 for cryptochlorogenic acid, 0.5058-129.5ngmL-1 for 3,5-dicaffeoylquinic acid, 0.3205-82.05ngmL-1 for 3,4-dicaffeoylquinic acid, 1.002-512.8ngmL-1 for isoforsythoside, 0.4795-982.1ngmL-1 for forsythoside A and 0.7587-776.9ngmL-1 for forsythoside B, respectively. The intra- and inter-batch precisions were all within 15% and the accuracy (relative error, RE%) all ranged from 85.68% to 114.7%. It was shown from pharmacokinetic parameters that the rank order of AUC0-t, Cmax and T1/2k for phenolic acids was chlorogenic acid>neochlorogenic acid≥cryptochlorogenic acid>3,4-dicaffeoylquinic acid≥3,5-dicaffeoylquinic acid (most of them had significant differences), which corresponded to their administration dosages to rats, but that of MRT0-t and T1/2z were opposite. Besides, the AUC0-t, Cmax, MRT and T1/2z except T1/2k of isoforsythoside and forsythoside B had no significant difference, compared to that of forsythoside A though their administration dosages were significantly lower than that of forsythoside A. All results showed that the method was applied to the pharmacokinetic study of the eight caffeic acid derivatives in rat plasma successfully after oral administration of Flos Lonicerae-Fructus Forsythiae herb combination, and there were significant differences of caffeic acid derivatives even isomers in the pharmacokinetic parameters. © 2014 Elsevier B.V.


Zhou W.,Nanjing University | Zhou W.,Jiangsu Engineering Research Center for Efficient Delivery System of TCM | 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.

Loading Jiangsu Engineering Research Center for Efficient Delivery System of TCM collaborators
Loading Jiangsu Engineering Research Center for Efficient Delivery System of TCM collaborators