Co-reporter:Xueju Zhang, Lu Wang, Zhong Zheng, Zifeng Pi, Zhiqiang Liu, Fengrui Song
Journal of Pharmaceutical and Biomedical Analysis 2017 Volume 140(Volume 140) pp:
Publication Date(Web):5 June 2017
DOI:10.1016/j.jpba.2017.03.040
•Online MD-UPLC-ESI–MS/MS method has been validated and applied success- fully to real-time and simultaneous determination of genipin, geniposide, gardenoside and geniposidic acid after oral administration of irioid extract from Gardenia Jasminoides Ellis.•It is the first time to elaborate and confirm that the pharmacokinetic differences of these iridoid compounds between healthy and type 2 diabetic rats.Iridoid glycosides consist the main bioactive constituents of Gardenia jasminoides Ellis (G. jasminoides), which is used alone or in combination with other medicine herbs for treatment of diabetes mellitus in China. This paper investigated for the first time comparative pharmacokinetics (PKs) of four unbound iridoids (including genipin, geniposide, gardenoside and geniposidic acid) in rat blood between healthy and type 2 diabetic groups with different disease progressions (9 or 13 weeks). Online microdialysis-ultra performance liquid chromatography-mass spectrometry (MD- UPLC–MS/MS) method was used after oral administration of iridoid extracts obtained from the fruits of G. jasminoides. Student's t-test was used for statistical comparison of PK parameters. Results showed that genipin, geniposide and geniposidic acid feature higher Cmax, larger area under the curve (AUC), lower clearance (CL), longer Tmax and mean residence time (MRT) in type 2 diabetic rats than those in healthy rats (p < 0.05). However, no significant difference was observed in PK parameters between the two diabetic groups with different complication progressions (p > 0.05). Type 2 diabetic rats showed significantly altered PK behaviors of genipin, geniposide and geniposidic acid (especially systemic exposure, AUCs of genipin, geniposide and geniposidic acid). Online MD-UPLC–MS/MS provides real-time sampling and monitoring, these functions can be applied to PKs of iridoids from G. jasminoides.Download high-res image (112KB)Download full-size image
Co-reporter:Xue Li, Zifeng Pi, Shu Liu, Wei Wang, Zhiqiang Liu, Fengrui Song
Journal of Chromatography B 2017 Volume 1063(Volume 1063) pp:
Publication Date(Web):15 September 2017
DOI:10.1016/j.jchromb.2017.08.012
•A system was established to online monitor the metabolism changes of astragaloside II in complex intestinal microbiota.•A homemade cultural device was built and used for metabolism reserch of astragaloside II in intestinal microbiota.•HP-β-CD was firstly used as an impurity removal agent in MD system.A new system was described for the online monitoring of astragaloside II (AII) metabolism in intestinal microbial community. The system was based on a homemade cultural device coupled with microdialysis (MD) and ultra-performance liquid chromatography–mass spectrometry (UPLC–MS). Main improvements include a simplified anaerobic incubator enabling the experiment to be conducted in ambient atmosphere, continuous sampling, and decreased matrix effect. Importantly, our method distinctly decreases the interference of small molecules by adding 20 mg ml−1 of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) to the perfusion fluid. Using the developed method, the metabolism of AII in intestinal bacteria was successfully investigated. Results were then compared with those obtained by conventional incubation and sampling method. We found that the integrated experimental system maintained the proper fermentation environment for bacteria and enabled high chromatography performance. With the advantages of auto-sampling, online detection, non-requirement of expensive fermenting equipment, and negligible matrix interference, the method can greatly contribute to the investigation of the dynamic biotransformation of astragalosides in complicated matrix-based biological samples.
Co-reporter:Guang-Yue Hou, Li-Hui Men, Lu Wang, Zhong Zheng, ... Zhong-Ying Liu
Chinese Chemical Letters 2017 Volume 28, Issue 6(Volume 28, Issue 6) pp:
Publication Date(Web):1 June 2017
DOI:10.1016/j.cclet.2016.12.039
The effect of Radix Scutellariae treated on type 2 diabetic rats has been investigated by a liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) based urinary quantitative approach. In this research, multiple reactions monitoring mode of MS/MS in LC–MS/MS analysis was used to quantitatively analyze the concentrations of 7 endogenous compounds in urine of normal control group, type 2 diabetic model group and Radix Scutellariae-treated group, and multivariate statistical analysis was utilized for MS data processing. The above-mentioned three groups can be distinguished via pattern recognition. The obtained results indicated that Radix Scutellariae affect the urinary metabolic profiling of type 2 diabetic rats on the polyol pathway, protein glycation reaction and amino acids metabolism pathway. According to these results, Radix Scutellariae should have the pharmacological effect on preventing or delaying the onset and progression of diabetes and its complications.Download high-res image (143KB)Download full-size imageLC–MS/MS quantitative analysis combined with multivariate statistical analysis is used for evaluating the metabolic response of Radix Scutellariaeon treated DM2 rats.
Co-reporter:Lu Wang, Shu Liu, Xueju Zhang, Junpeng Xing, Zhiqiang Liu, Fengrui Song
Journal of Chromatography A 2016 Volume 1452() pp:47-57
Publication Date(Web):24 June 2016
DOI:10.1016/j.chroma.2016.05.026
•HPLC-ESI-MS/MS combined with IMS-MS method has been established.•71 components in the fruits of G. Jasminoides were identified or presumed.•AB-8 macroporous resins and C18 HPLC orthogonal column separation increased chromatographic peak capacity.•Ion mobility separation (IMS) was employed as a supplementary separation technique to discover new natural isomers.In this paper, an analysis strategy integrating macroporous resin (AB-8) column chromatography and high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) combined with ion mobility spectrometry (IMS) was proposed and applied for identification and structural characterization of compounds from the fruits of Gardenia jasminoides. The extracts of G. jasminoides were separated by AB-8 resin column chromatography combined with reversed phase liquid chromatography (C18 column) and detected by electrospray ionization tandem mass spectrometry. Additionally, ion mobility spectrometry (IMS) was employed as a supplementary separation technique to discover previously undetected isomers from the fruits of G. jasminoides. A total of 71 compounds, including iridoids, flavonoids, triterpenes, monoterpenoids, carotenoids and phenolic acids were identified by the characteristic high resolution mass spectrometry and the ESI-MS/MS fragmentations. In conclusion, the IMS-MS technique achieved the separation of isomers in crocin-3 and crocin-4 according to their acquired mobility drift times differing from classical analysis by mass spectrometry. The proposed strategy can be used as a highly sensitive and efficient procedure for identification and separation isomeric components in extracts of herbal medicines.
Co-reporter:Ruixing Zhang;Xiaoyu Zhuang;Li Zong;Shu Liu
Analytical and Bioanalytical Chemistry 2016 Volume 408( Issue 21) pp:5843-5854
Publication Date(Web):2016 August
DOI:10.1007/s00216-016-9696-4
Although anticancer drug resistance has been linked to high expression of P-glycoprotein and the enhanced DNA repair ability, the biochemical process and the underlying mechanisms of drug resistance are not clear. In order to clarify the biochemical mechanisms of drug resistance during anticancer drug treatment, we studied the metabolomics of MCF-7/S and MCF-7/Adr cell lines, the COC1 and COC1/DDP cell lines, including the metabolic pathways of multidrug-resistant tumor cells and the changes of endogenous substances in cells. The intracellular metabolites were profiled using ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS). In this study, 24 biomarkers in MCF-7/Adr cells and 15 biomarkers in COC1/DDP cells that are involved in some important metabolic pathways were putatively identified. Several metabolic pathways are changed in tumor cells showing drug resistance, such as protein synthesis pathways, cysteine synthesis, the glutamine metabolic pathway, and the ammonia cycle; the first of these are involved in the synthesis of some important proteins including membrane proteins, multidrug resistance-associated proteins, and P-glycoprotein (P-gp). Proteins related to drug resistance were overexpressed in multidrug-resistant tumor cells. These proteins depended on energy and play important roles in the emergence of drug resistance. The changes in glutathione and cysteine metabolic pathways showed that the cells can activate related metabolic pathways and reduce the cell apoptosis when they encounter oxidative damage. These findings indicate that drug resistance is likely associated with increased P-gp synthesis and reduced apoptosis of tumor cells.
Co-reporter:Lu Wang, Shu Liu, Zhong Zheng, Zifeng Pi, Fengrui Song and Zhiqiang Liu
Analytical Methods 2015 vol. 7(Issue 4) pp:1535-1542
Publication Date(Web):23 Dec 2014
DOI:10.1039/C4AY02690J
As a result of the donation of one electron, superoxide anion radicals (O2˙−) are produced in vivo, which are closely linked with several diseases in humans. In the past decades, some analytical methods for the determination of O2˙− scavenging capacity have been established. The most common methods in vitro are spectrum-based microplate screening assay using nitroblue tetrazolium (NBT) or cytochrome c as the target/probe for evaluating O2˙− scavenging activity. The target/probe is spectrophotometrically monitored at the ultraviolet-vis (UV-vis) region in the analysis of the samples with restraining UV-vis absorption. Nevertheless, the results of these methods were severely compromised when they were applied to analyze the samples with strong absorption in the visible region, such as natural pigments. To solve these problems, a simple and rapid assay combined with a new probe, a highly water-soluble tetrazolium salt, 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium sodium salt (WST-1) and ultra-high performance liquid chromatography-diode-array detection (UPLC-DAD) method was developed. Above all, this method could be adapted to samples of strong absorption in the visible region. In this study, the superoxide anion radical scavenging activities of various natural pigments were evaluated.
Co-reporter:Xiudong Yang;Xue Li;Ying Xu;Zifeng Pi;Na Lin;Zhiqiang Liu;Fengrui Song
Chinese Journal of Chemistry 2015 Volume 33( Issue 9) pp:1069-1076
Publication Date(Web):
DOI:10.1002/cjoc.201500307
Abstract
In traditional Chinese medicine theory, Panax ginseng and Veratrum nigrum L. is an important incompatible herb pair. Studies on the content variation of main components and the influences on the metabolism in rat intestinal bacteria are useful to understand the mechanism of incompatibility of this herb pairs. In this study, the content variation of ginsenosides and their metaboltic profiles in the extracts of P. ginseng and compatibility of P. ginseng with V. nigrum L. (G-V) were investigated using relative quantitative method of electrospray ionization mass spectrometry (ESI-MS) and UPLC-MSn, respectively. The relative contents of most ginsenosides were reduced in the extract of G-V. Furthermore, ginsenosides Rb1, Rb2, Rc and Rd could be metabolized to Rd, F2 and C-K in rat intestinal bacteria. The metabolic speeds of Rb1, Rb2 and Rc in the G-V extracts at ratios of 10:5, 10:7 and 10:10 and the metabolic rates of ginsenosides Rb1, Rb2 and Rc to Rd, Rd to F2 in all compatibility extracts were lower than that in the P. ginseng extract. In conclusion, this study illustrated the mechanism of effect-reducing by comparison of the relative contents and metabolic profiles of ginsenosides after compatibility of P. ginseng and V. nigrum L.
Co-reporter:Feng Zhou;Hongbin Zhu;Shu Liu;Kang Ma;Fengrui Song;Zhiqiang Liu
Chinese Journal of Chemistry 2015 Volume 33( Issue 2) pp:241-246
Publication Date(Web):
DOI:10.1002/cjoc.201400692
Abstract
In this study, an extend application was developed to in situ analyze the herbal pieces of Aconitum plants by Direct Analysis in Real Time Mass Spectrometry (DART-MS). Nearly all aconitine-type alkaloids can be desorbed and ionized in this method, including diester diterpenoid aconitines (DDAs), monoester diterpenoid aconitines (MDAs) and some other diterpenoid aconitines. The spectra of in situ analysis for the herbal pieces of aconitum plants are similar with that of their extracts. Radix Aconiti and Radix Aconiti Kusnezoffii can be distinguished from each other by the intensity differences of character fragment ions from MDAs, such as m/z 586, 572, and 556. The qualified and unqualified herbal pieces can be also identified by the relative abundances of DDAs. The RSD of the relative abundances of some character ions at m/z 556, 586, and 590 were 13.53%, 4.03%, and 12.03%, respectively. So this in situ analytical method can identify both the types of Aconitum preparata and their quality. It provides the following advantages in the analysis of Chinese herbs: fast detection without much pretreatment, high-throughput analysis, and reduction of pollution without any organic solvent.
Co-reporter:Ruixing Zhang, Xiaoyu Zhuang, Shu Liu, Fengrui Song and Zhiqiang Liu
Analytical Methods 2014 vol. 6(Issue 15) pp:5746-5752
Publication Date(Web):27 May 2014
DOI:10.1039/C4AY00771A
An electrospray ionization-tandem mass spectrometry (ESI-MS/MS) strategy was developed for the detection of mercury ion with high sensitivity and selectivity based on a competition system of glutathione and mercury specific DNA to mercury ion. Mercury ion selectively bound to a special mismatched DNA and glutathione (GSH) because thiol-containing tripeptide can effectively sequester Hg2+ ion from thymine–Hg2+–thymine structure. Following the competition reaction, the concentration of mercury ion in the analyte was indirectly reflected by monitoring the concentration change of free GSH by ESI-MS/MS method. The electrospray ionization-mass spectrometry (ESI-MS) analysis of the competition system provided the connection of mercury ion and mercury specific DNA (MSD), and also provided the process by which GSH competed mercury ion from MSD. Note that the proposed competing platform exhibits exquisite selectivity and sensitivity to Hg2+ ion with a detection limit of 5 nM. Furthermore, this assay design avoids the labeling of the probe, use of the quantum dot, fluorescence dye, and heavy metals. Therefore, it is much friendlier for the operators and the environment. The proposed method was applied to some real samples (tap water, lake water, and fish), and the obtained results were satisfactory.
Co-reporter:Guang-Yue Hou, Lu Wang, Shu Liu, Feng-Rui Song, Zhi-Qiang Liu
Chinese Chemical Letters 2014 Volume 25(Issue 7) pp:1039-1043
Publication Date(Web):July 2014
DOI:10.1016/j.cclet.2014.04.029
The formation of advanced glycation end-products (AGEs) and aldose reductase (AR) activity have been implicated in the development of diabetic complications. Our study sought to characterize the capacities of eleven herbal extracts against the formation of AGEs and the AR activity. An ultrahigh performance liquid chromatography and tandem mass spectrometry (UPLC–MS/MS) method was used for the detection of AR activity and the screening of AR inhibitors in this research. The amount of sorbitol from each analyte was directly detected using the multiple reaction monitoring mode and the sorbitol level could be reduced via the addition of an inhibitor. Moreover, the BSA/glucose (fructose) system was applied to investigate their inhibitory activities of AGEs formation in glycation model reactions. Compared with other screened herbs used in our study, Flos Sophorae Immaturus and Radix Scutellariae seemed to be more effective on inhibiting the formation of AGEs and AR activity. The inhibiting capacities of herbal extracts against AR activity and AGEs formation may be correlated with the bioactive components of the herbal extracts. The differences were correlated with the amount of polyphenol and flavonoid components. In the study, we have investigated the potential anti-hyperglycemic bioactivity of eleven herbal extracts in vitro, which could provide a reference for further in vivo research in the prevention and treatment of diabetic complications.Inhibitors of advanced glycation end-products formation and aldose reductase activity have been considered as potential treatment of diabetic complications. Considering these two aspects, the capacities of eleven herbal extracts were investigated with respect to the potential prevention and treatment of diabetic complications.
Co-reporter:Guangyue Hou, Ruixing Zhang, Zifeng Pi, Fengrui Song, Zhiqiang Liu and Shuying Liu
Analytical Methods 2014 vol. 6(Issue 19) pp:7681-7688
Publication Date(Web):30 Jun 2014
DOI:10.1039/C4AY00857J
In this study, an ultrahigh performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS) method was developed for the detection of aldose reductase (AR) activity and the screening of AR inhibitors in vitro. Glucose was chosen as the substrate of the enzymatic reaction system according to the polyol pathway. In the polyol pathway, glucose could be converted into sorbitol. The multiple reaction monitoring (MRM) mode was used to directly detect the level of sorbitol from each analyte and the amount of sorbitol could be reduced via the addition of an inhibitor. The proposed approach had been successfully applied to determine the AR inhibitory activities of epalrestat, flavonoids and natural product extracts. Additionally, we proposed a detailed discussion of the structure–activity relationships of flavonoids according to the inhibitory activities of thirty-two flavonoids. The screening method proposed in our study was similar to the metabolic pathway in diabetic patients and could eliminate the interference of other substances. We could envision that our method could be used for the screening of AR inhibitors as drugs for the treatment of related diabetic complications.
Co-reporter:Xueju Zhang, Shu Liu, Zifeng Pi, Zhiqiang Liu, Fengrui Song
Journal of Chromatography B (15 January 2017) Volumes 1041–1042() pp:
Publication Date(Web):15 January 2017
DOI:10.1016/j.jchromb.2016.12.010
•A breakthrough of the simultaneous quantification of major metabolites from herb medicines was achieved without standard compounds using online mircrodialysis-ultra performance liquid chromatography-mass spectrometry.•It is the first time to investigate the compare pharmacokinetics of two major metabolites, namely, genipin-1-o-glucuronic acid and genipin-monosulfate from geniposide and genipin between healthy and diabetic rats by online MD-UPLC–MS/MS. The results showed that their pharmacokinetic behaviors in type 2 diabetic rats significantly differ from healthy rats (p < 0.05).•The approach could predict druggability of bioactive metabolites from their prototypes.Genipin-1-o-glucuronic acid and genipin-monosulfate are two major metabolites from geniposide and genipin. Based on diabetic rat model, we developed a simultaneous quantification method to investigate their comparative pharmacokinetics by online mircrodialysis-ultra performance liquid chromatography–mass spectrometry (MD-UPLC–MS/MS) without their standard compounds. Online microdialysis sampling could avoid unexpected contamination or degradation of the analytes during the storage and transfer steps. Combined with good sensitivity, selectivity and selectivity of UPLC–MS/MS, online MD-UPLC–MS/MS method could real-timely monitor metabolites in rat blood for quantitative analysis. Our research found that AUC0→t of genipin-1-o-glucuronic acid and genipin-monosulfate in blood of diabetic group were 17.68 and 7.58 times than those in normal group, respectively, and AUC0→t of genipin-1-o-glucuronic acid was 2.28 times than that of genipin-monosulfate in blood of diabetic group, which revealed the effect of diabetes on the pharmacokinetic properties of the two metabolites. This study not only provides an approach for pharmacokinetic studies for various metabolites from herb medicines, but also can predict druggability of their bioactive metabolites. The insight obtained should facilitate drug development and toxicity research.
Co-reporter:
Analytical Methods (2009-Present) 2014 - vol. 6(Issue 19) pp:
Publication Date(Web):
DOI:10.1039/C4AY00857J
In this study, an ultrahigh performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS) method was developed for the detection of aldose reductase (AR) activity and the screening of AR inhibitors in vitro. Glucose was chosen as the substrate of the enzymatic reaction system according to the polyol pathway. In the polyol pathway, glucose could be converted into sorbitol. The multiple reaction monitoring (MRM) mode was used to directly detect the level of sorbitol from each analyte and the amount of sorbitol could be reduced via the addition of an inhibitor. The proposed approach had been successfully applied to determine the AR inhibitory activities of epalrestat, flavonoids and natural product extracts. Additionally, we proposed a detailed discussion of the structure–activity relationships of flavonoids according to the inhibitory activities of thirty-two flavonoids. The screening method proposed in our study was similar to the metabolic pathway in diabetic patients and could eliminate the interference of other substances. We could envision that our method could be used for the screening of AR inhibitors as drugs for the treatment of related diabetic complications.
Co-reporter:
Analytical Methods (2009-Present) 2014 - vol. 6(Issue 15) pp:
Publication Date(Web):
DOI:10.1039/C4AY00771A
An electrospray ionization-tandem mass spectrometry (ESI-MS/MS) strategy was developed for the detection of mercury ion with high sensitivity and selectivity based on a competition system of glutathione and mercury specific DNA to mercury ion. Mercury ion selectively bound to a special mismatched DNA and glutathione (GSH) because thiol-containing tripeptide can effectively sequester Hg2+ ion from thymine–Hg2+–thymine structure. Following the competition reaction, the concentration of mercury ion in the analyte was indirectly reflected by monitoring the concentration change of free GSH by ESI-MS/MS method. The electrospray ionization-mass spectrometry (ESI-MS) analysis of the competition system provided the connection of mercury ion and mercury specific DNA (MSD), and also provided the process by which GSH competed mercury ion from MSD. Note that the proposed competing platform exhibits exquisite selectivity and sensitivity to Hg2+ ion with a detection limit of 5 nM. Furthermore, this assay design avoids the labeling of the probe, use of the quantum dot, fluorescence dye, and heavy metals. Therefore, it is much friendlier for the operators and the environment. The proposed method was applied to some real samples (tap water, lake water, and fish), and the obtained results were satisfactory.
![(6R,7S)-1,2,11,12-tetramethoxy-6,7-dimethyl-5,6,7,8-tetrahydrodibenzo[a,c][8]annulene-3,10-diol](http://img.cochemist.com/ccimg/66300/66280-25-9.png)
![(6R,7S)-1,2,11,12-tetramethoxy-6,7-dimethyl-5,6,7,8-tetrahydrodibenzo[a,c][8]annulene-3,10-diol](http://img.cochemist.com/ccimg/66300/66280-25-9_b.png)
