Li Yang

Shanghai University of Traditional Chinese Medicine, Shanghai, Shanghai Shi, China

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Publications (109)215.03 Total impact

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    ABSTRACT: Yin-Chen-Hao-Tang (YCHT), a commonly used as a traditional chinese medicine for liver disease. Several studies indicated that YCHT may improving hepatic triglyceride metabolism and anti-apoptotic response as well as decreasing oxidative stress .However, little is known about the role of YCHT in chlorpromazine (CPZ) -induced chlolestatic liver injury. Therefore, we aimed to facilitate the understanding of the pathogenesis of cholestatic liver injury and evaluate the effect of Yin-Chen-Hao-Tang (YCHT) on chlorpromazine (CPZ)-induced cholestatic liver injury in rats based on the change of bile acids (BAs) and free fatty acids (FFAs) alone with the biochemical indicators and histological examination. We conducted an experiment on CPZ-induced cholestatic liver injury in Wistar rats with and without YCHT for nine consecutive days. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), total bilirubin (TBIL), total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C) were measured to evaluate the protective effect of YCHT against chlorpromazine (CPZ)-induced cholestatic liver injury. Histopathology of the liver tissue showed that pathological injuries were relieved after YCHT pretreatment. In addition, ultra-performance lipid chromatography coupled with quadrupole mass spectrometry (UPLC-MS) and gas chromatography coupled with mass spectrometry (GC-MS) was applied to determine the content of bile acids, free fatty acids, respectively. Obtained data showed that YCHT attenuated the effect of CPZ-induced cholestatic liver injury, which was manifested by the serum biochemical parameters and histopathology of the liver tissue. YCHT regulated the lipid levels as indicated by the reversed serum levels of TC, TG, and LDL-C. YCHT also regulated the disorder of BA and FFA metabolism by CPZ induction. Results indicated that YCHT exerted a protective effect on CPZ-induced cholestasis liver injury. The variance of BA and FFA concentrations can be used to evaluate the cholestatic liver injury caused by CPZ and the hepatoprotective effect of YCHT.
    BMC Complementary and Alternative Medicine 04/2015; 15(1):122. DOI:10.1186/s12906-015-0627-2 · 1.88 Impact Factor
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    ABSTRACT: Notoginsenoside Fc (NGFc) is a protopanaxadiol-type (PPD-type) saponin from Panax notoginseng, which has perfect anti-platelet aggregatory effect. However, its pharmacokinetics and metabolism in vivo remain unknown. In this study, a simple and sensitive liquid chromatography/electrospray ionization tandem mass spectrometry (LC-MS/MS) method was first developed for the determination of NGFc in rat plasma. After methanol-mediated protein precipitation, separation was achieved on a C18 column with MS detection operated in negative SRM mode at m/z 604.56→m/z 783.90 and m/z 799.93→m/z 637.64 for NGFc and IS, respectively. The assay was linear over the concentration range (r>0.995) with the LLOQ of 0.002μg/ml. The intra- and inter-day precisions (R.S.D.) were 2.45-12.36% and 3.67-14.22%, respectively; whereas accuracy ranged from (R.R.) 93.90% to 99.41%. The extraction recovery, stability, and matrix effect were within the acceptable limits. The validated LC-MS/MS method was successfully applied to the pre-clinical pharmacokinetic studies of NGFc in rat. After oral and intravenous administration, NGFc showed dose-independent pharmacokinetic behaviors with a t1/2 of >22h and its oral bioavailability was 0.10-0.14%. In addition, a total of 10 metabolites were detected and structurally characterized by UPLC-Q/TOF-MS technique, which suggested that deglycosylation was the major metabolic pathway for NGFc in rats. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
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    ABSTRACT: Bile acids (BAs) are not only digestive surfactants but also important cell signaling molecules, which stimulate several signaling pathways to regulate some important biological processes. The bile-acid-activated nuclear receptor, farnesoid X receptor (FXR), plays a pivotal role in regulating bile acid, lipid and glucose homeostasis as well as in regulating the inflammatory responses, barrier function and prevention of bacterial translocation in the intestinal tract. As expected, FXR is involved in the pathophysiology of a wide range of diseases of gastrointestinal tract, including inflammatory bowel disease, colorectal cancer and type 2 diabetes. In this review, we discuss current knowledge of the roles of FXR in physiology of the digestive system and the related diseases. Better understanding of the roles of FXR in digestive system will accelerate the development of FXR ligands/modulators for the treatment of digestive system diseases.
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    ABSTRACT: Curcumin, a principle bioactive component of Curcuma longa L, is well known for its anti-hyperlipidemia effect. However, no holistic metabolic information of curcumin on hyperlipidemia models has been revealed, which may provide us an insight into the underlying mechanism. In the present work, NMR and MS based metabolomics was conducted to investigate the intervention effect of curcumin on hyperlipidemia mice induced by high-fat diet (HFD) feeding for 12 weeks. The HFD induced animals were orally administered with curcumin (40, 80 mg/kg) or lovastatin (30 mg/kg, positive control) once a day during the inducing period. Serum biochemistry assay of TC, TG, LDL-c, and HDL-c was conducted and proved that treatment of curcumin or lovastatin can significantly improve the lipid profiles. Subsequently, metabolomics analysis was carried out for urine samples. Orthogonal Partial Least Squares-Discriminant analysis (OPLS-DA) was employed to investigate the anti-hyperlipidemia effect of curcumin and to detect related potential biomarkers. Totally, 35 biomarkers were identified, including 31 by NMR and nine by MS (five by both). It turned out that curcumin treatment can partially recover the metabolism disorders induced by HFD, with the following metabolic pathways involved: TCA cycle, glycolysis and gluconeogenesis, synthesis of ketone bodies and cholesterol, ketogenesis of branched chain amino acid, choline metabolism, and fatty acid metabolism. Besides, NMR and MS based metabolomics proved to be powerful tools in investigating pharmacodynamics effect of natural products and underlying mechanisms.
    PLoS ONE 01/2015; 10(3):e0120950. DOI:10.1371/journal.pone.0120950 · 3.53 Impact Factor
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    ABSTRACT: This paper utilized a quantitative (1)H nuclear magnetic resonance (qHNMR) method for assessing the purity of iridoids and secoiridoids. The method was fully validated, including specificity, linearity, accuracy, precision, reproducibility, and robustness. For optimization of experimental conditions, several experimental parameters were investigated, including relaxation delay (D1), scan numbers (NS) and power length (PL1). The quantification was based on the area ratios of H-3 from analytes relative to aromatic protons from 1, 4-dinitrobenzene (internal standard) with methanol-d4 as solvent. Five iridoids and secoiridoids (sweroside, swertiamarin, gentiopicroside, geniposide, genipin) were analyzed. Furthermore, the results were validated by the high performance liquid chromatography coupled with ultraviolet detection (HPLC-UV) method. It can be concluded that the qHNMR method was simple, rapid, and accurate, providing a reliable and superior method for assessing the purity of iridoids and secoiridoids. Copyright © 2014. Published by Elsevier B.V.
    Fitoterapia 12/2014; 100. DOI:10.1016/j.fitote.2014.12.001 · 2.22 Impact Factor
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    ABSTRACT: Gigantol is a typical bibenzyl compound isolated from Dendrobii Caulis that has been widely used as a medicinal herb in China for the treatment of diabetic cataract, cancer and arteriosclerosis obliterans and as a tonic for stomach nourishment, saliva secretion promotion and fever reduction. However, few studies have been carried out on its in vivo metabolism. In the present study, a rapid and sensitive method based on ultra-performance liquid chromatography/electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-Q/TOF-MS) in positive ion mode was developed and applied to identify the metabolites of gigantol in rat urine after a single oral dose (100 mg/kg). Chromatographic separation was performed on an Acquity UPLC HSS T3 column (100 × 2.1 mm i. d., 1.8 µm) using acetonitrile and 0.1% aqueous formic acid as mobile phases. A total of 11 metabolites were detected and identified as all phase II metabolites. The structures of the metabolites were identified based on the characteristics of their MS, MS(2) data and chromatographic retention times. The results showed that glucuronidation is the principal metabolic pathway of gigantol in rats. The newly identified metabolites are useful to understand the mechanism of elimination of gigantol and, in turn, its effectiveness and toxicity. As far as we know, this is the first attempt to investigate the metabolic fate of gigantol in vivo. Copyright © 2014 John Wiley & Sons, Ltd.
    Biomedical Chromatography 12/2014; 28(12). DOI:10.1002/bmc.3224 · 1.66 Impact Factor
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    ABSTRACT: Sweroside, a major active iridoid in Swertia pseudochinensis Hara, is recognized as an effective agent in the treatment of liver injury. Based on previous reports, the relatively short half-life (64 min) and poor bioavailability (approximately 0.31%) in rats suggested that not only sweroside itself but also its metabolites could be responsible for the observed hepato-protective effect. However, few studies have been carried out on the metabolism of sweroside. Therefore, the present study aimed at identifying the metabolites of sweroside in rat urine after a single oral dose (100 mg/kg). With ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC/Q-TOF-MS), the metabolic profile revealed 11 metabolites in rat urine, including phase I, phase II and aglycone-related products. The chemical structures of metabolites were proposed based on accurate mass measurements of protonated or deprotonated molecules and their fragmentation patterns. Our findings showed that the aglycone of sweroside (M05) and its glucuronide conjugate (M06) were principal circulating metabolites in rats. While several other metabolic transformations, occurring via reduction, N-heterocyclization and N-acetylation after deglycosylation, were also observed. Two metabolites (M05 and M06) were isolated from the rat urine for structural elucidation and identifcation of reaction sites. Both M05 and M06 were characterized by 1H, 13C and two-dimensional nuclear magnetic resonance (NMR) spectroscopy. UHPLC/Q-TOF-MS analysis has provided an important analytical platform to gather metabolic profile of sweroside. Copyright © 2014 John Wiley & Sons, Ltd.
    Journal of Mass Spectrometry 11/2014; 49(11). DOI:10.1002/jms.3429 · 2.71 Impact Factor
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    ABSTRACT: A novel comprehensive method with supercritical sluid chromatography-photodiode array detector-mass spectrometry (SFC-PDA-MS) was developed for the qualitative and quantitative analyses of chiral isomer pair in Ban Lan Gen (dried root of Isatis indigotica) and processed product. A standard goitrin/epigoitrin racemic mixture was used for method development. A total of six chiral stationary phases (CSPs) were screened and the (S, S)-Whelk-O 1 (4.6 ´ 250 mm, 10 μm) column was chosen as it offers the baseline resolution for the enantiomeric pair with separation accomplished in 6 minutes. A single quadrupole MS and a PDA detector were used in line for the detection. The validated method was applied successfully in the analysis of different samples. Results indicated that the developed assay was fast, sensitive and reproducible. SFC should be an integral part of the overall analytical platform for TCM and natural product research, especially in the area of chiral analysis.
    RSC Advances 09/2014; 4(90). DOI:10.1039/C4RA02705A · 3.71 Impact Factor
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    ABSTRACT: The toxicity assessment of herbal medicines is important for human health and appropriate utilization of these medicines. However, challenges have to be overcome because of the complexity of coexisting multiple components in herbal medicines and the highly interconnected organismal system. In this study, a target profiling approach was established by combining the characteristic fingerprint analysis of herbal chemicals with potential toxicity through a precursor ion scan-based mass spectroscopy and the target profiling analysis of biomarkers responsible for the toxicity. Through this newly developed approach, the comparative hepatotoxicity assessment of two herbal medicines from the same genus, Senecio vulgaris L. and Senecio scandens Buch.-Ham, was performed. Significant differences were found between the two species in their chemical markers (i.e., pyrrolizidine alkaloids) and biomarkers (i.e., bile acids) responsible for their toxicities. This result was consistent with the conventional toxicity assessment conducted by histopathological examination and clinical serum index assay on experimental animal models. In conclusion, this study provided a new approach for the hepatotoxicity assessment of herbal medicines containing pyrrolizidine alkaloids, which are widely distributed in various herbal medicines. The target profiling approach may shed light on the toxicity assessment of other herbal medicines with potential toxicity.
    Analytical and Bioanalytical Chemistry 09/2014; DOI:10.1007/s00216-014-8175-z · 3.58 Impact Factor
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    ABSTRACT: Sterol regulatory element-binding proteins (SREBPs) are major transcription factors regulating the expression of genes involved in biosynthesis of cholesterol, fatty acid and triglyceride. We investigated the effect of the specific SREBP suppressor andrographolide, a natural compound isolated from Andrographis paniculata, on the regulation of SREBP signaling by western blot, reporter gene assay and Q-PCR analysis. In addition, the anti-obesity effects of andrographolide were evaluated in C57BL/6 mice with high-fat diet (HFD)-induced obesity. Our results showed that andrographolide downregulated the expressions of SREBPs target genes and decreases cellular lipid accumulation in vitro. Further, andrographolide (100 mg/kg/day) attenuated HFD-induced body weight gain and fat accumulation in liver or adipose tissues, and improved serum lipid levels and insulin or glucose sensitivity in HFD-induced obese mice. Meanwhile, andrographolide effectively suppressed the respiratory quotient (RQ), energy expenditure (EE) and their oxygen consumption, which might contribute to the decreased body-weight gain of the obese mice fed with a HFD. Consistently, andrographolide regulates SREBPs target genes and metabolism associated genes in liver or brown adipose tissue (BAT), which may directly contribute to the lower lipid level and enhanced insulin sensitivity. Take together, andrographolide ameliorates lipid metabolism and improved glucose utilization in the HFD-induced obesity mice. Therefore, andrographolide could be a potential leading compound used for the prevention or treatment of obesity and insulin resistance.
    Journal of Pharmacology and Experimental Therapeutics 09/2014; DOI:10.1124/jpet.114.217968 · 3.86 Impact Factor
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    ABSTRACT: Diabetic retinopathy (DR) is the most common and serious complication of diabetes mellitus (DM). The present study investigates the amelioration of ethanol extract of Dendrobium chrysotoxum Lindl (DC) on streptozotocin (STZ)-induced DR and its engaged mechanism. Retinal immunofluorescence staining with cluster of differentiation 31 (CD31) demonstrated that DC (30-300mg/kg) decreased the increased retinal vessels in STZ-induced diabetic rats. Retinal histopathological observation also showed that retinal vessels were decreased in DC-treated diabetic rats. DC decreased the increased retinal mRNA expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) in diabetic rats, and DC also decreased the elevated serum VEGF level. Immunohistochemical staining further evidenced that DC decreased VEGF and VEGFR2 expression in retinas. Retinal mRNA expression of matrix metalloproteinase (MMP) 2 /9 was decreased in DC (300mg/kg)-treated diabetic rats. Serum levels of MMP 2/9, basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF) A/B, insulin-like growth factor 1 (IGF-1), interleukin 1β (IL-1β), and IL-6 were all decreased in DC-treated diabetic rats. In addition, DC decreased the increased phosphorylation of p65 and the increased expression of intercellular adhesion molecule-1 (ICAM-1). In conclusion, DC can alleviate retinal angiogenesis during the process of DR via inhibiting the expression of VEGF/VEGFR2, and some other pro-angiogenic factors such as MMP 2/9, PDGF A/B, bFGF, IGF-1. In addition, DC can also ameliorate retinal inflammation via inhibiting NFκB signaling pathway.
    Vascular Pharmacology 09/2014; DOI:10.1016/j.vph.2014.04.007 · 4.62 Impact Factor
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    ABSTRACT: To investigate the chemical constituents of the leaves of Clerodendrum trichotomum. The chemical constituents of petroleum ether extract of the leaves of Clerodendrum trichotomum were isolated and purified by various chromatographic techniques, such as silica gel, ODS, Sephadex LH-20, semi-preparative HPLC and recrystallization. The structures of these isolated compounds were identified by spectroscopic analysis (1 H-NMR,13 C-NMR,2D-NMR and MS). Ten compounds were isolated and identified from petroleum ether extract, containing four triterpenes, lupeol(1), friedelin(2), betulinic acid(3) and taraxerol(4); four sterols, 22-dehydroclerosterol(5), clerosterol(6), stigmasterol(7) and sitosterol(8); one diterpenoid, transphytol(9), and one alkaloid, 1H-indole-3-carboxylic acid(10). Compound 10 is obtained from the genus Clerodendrum for the first time, and seven compounds (1,3-4, and 7-10) are firstly isolated from this plant.
    Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials 09/2014; 37(9):1590-3.
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    ABSTRACT: Retinoic acid (RA) and bile acids share common roles in regulating lipid homeostasis and insulin sensitivity. In addition, the receptor for RA (retinoid x receptor) is a permissive partner of the receptor for bile acids, farnesoid x receptor (FXR/NR1H4). Thus, RA can activate the FXR-mediated pathway as well. The current study was designed to understand the effect of all-trans RA on bile acid homeostasis. Mice were fed an all-trans RA-supplemented diet and the expression of 46 genes that participate in regulating bile acid homeostasis was studied. The data showed that all-trans RA has a profound effect in regulating genes involved in synthesis and transport of bile acids. All-trans RA treatment reduced the gene expression levels of Cyp7a1, Cyp8b1, and Akr1d1, which are involved in bile acid synthesis. All-trans RA also decreased the hepatic mRNA levels of Lrh-1 (Nr5a2) and Hnf4α (Nr2a1), which positively regulate the gene expression of Cyp7a1 and Cyp8b1. Moreover, all-trans RA induced the gene expression levels of negative regulators of bile acid synthesis including hepatic Fgfr4, Fxr, and Shp (Nr0b2) as well as ileal Fgf15. All-trans RA also decreased the expression of Abcb11 and Slc51b, which have a role in bile acid transport. Consistently, all-trans RA reduced hepatic bile acid levels and the ratio of CA/CDCA, as demonstrated by liquid chromatography-mass spectrometry. The data suggest that all-trans RA-induced SHP may contribute to the inhibition of CYP7A1 and CYP8B1, which in turn reduces bile acid synthesis and affects lipid absorption in the gastrointestinal tract.
    Biochemical Pharmacology 08/2014; DOI:10.1016/j.bcp.2014.08.018 · 4.65 Impact Factor
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    ABSTRACT: Pyrrolizidine alkaloids are highly hepatotoxic natural chemicals that produce irreversible chronic and acute hepatotoxic effects on human beings. Purification of large amounts of pyrrolizidine alkaloids is necessary for toxicity studies. In this study, an efficient method for targeted analysis and purification of pyrrolizidine alkaloid cis/trans isomers from herbal materials was developed for the first time. Targeted analysis of the hepatotoxic pyrrolizidine alkaloids was performed by liquid chromatography with tandem mass spectrometry (precursor ion scan and daughter ion scan), and the purification of pyrrolizidine alkaloids was achieved with a mass-directed auto purification system. The extraction and preparative liquid chromatography conditions were optimized. The developed method was applied to analysis of Gynura japonica (Thunb.) Juel., a herbal medicine traditionally used for detumescence and relieving pain but is potentially hepatotoxic as it contains pyrrolizidine alkaloids. Twelve pyrrolizidine alkaloids (six cis/trans isomer pairs) were identified with reference compounds or characterized by liquid chromatography with tandem mass spectrometry, and five individual pyrrolizidine alkaloids, including (E)-seneciphylline, seneciphylline, integerrimine, senecionine, and seneciphyllinine, were prepared from G. japonica roots with high efficiency. The results of this work provide a new technique for the preparation of large amounts of pyrrolizidine alkaloid reference substances, which will also benefit toxicological studies of pyrrolizidine alkaloids and treatments for pyrrolizidine alkaloid-induced toxicity. This article is protected by copyright. All rights reserved.
    Journal of Separation Science 08/2014; 37(15). DOI:10.1002/jssc.201400314 · 2.59 Impact Factor
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    ABSTRACT: The Danning tablets (DNts) is commonly prescribed in China as a cholagogic formula. Our previous studies showed that DNts exerted the protective effect on alpha-naphthylisothiocyanate (ANIT)-induced liver injury with cholestasis in a dose-dependent mannar. However, the detailed molecular mechanisms of DNts against ANIT-induced cholestasis are still not fully explored.
    BMC Complementary and Alternative Medicine 07/2014; 14(1):249. DOI:10.1186/1472-6882-14-249 · 1.88 Impact Factor
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    ABSTRACT: Six new diterpenoids, 4-epi-7α-O-acetylscoparic acid A (1), 7α-hydroxyscopadiol (2), 7α-O-acetyl-8,17β-epoxyscoparic acid A (3), neo-dulcinol (4), dulcinodal-13-one (5), and 4-epi-7α-hydroxydulcinodal-13-one (6), and a new flavonoid, dillenetin 3-O-(6″-O-p-coumaroyl)-β-d-glucopyranoside (10), along with 12 known compounds, were isolated from the aerial parts of Scoparia dulcis. The 7S absolute configuration of the new diterpenoids 1-4 and 6 was deduced by comparing their NOESY spectra with that of a known compound, (7S)-4-epi-7-hydroxyscoparic acid A (7), which was determined by the modified Mosher's method. The flavonoids scutellarein (11), hispidulin (12), apigenin (15), and luteolin (16) and the terpenoids 4-epi-scopadulcic acid B (9) and betulinic acid (19) showed more potent α-glucosidase inhibitory effects (with IC50 values in the range 13.7-132.5 μM) than the positive control, acarbose. In addition, compounds 1, 11, 12, 15, 16, and acerosin (17) exhibited peroxisome proliferator-activated receptor gamma (PPAR-γ) agonistic activity, with EC50 values ranging from 0.9 to 24.9 μM.
    Journal of Natural Products 06/2014; 77(7). DOI:10.1021/np500150f · 3.95 Impact Factor
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    ABSTRACT: Introduction Dencichine, one of the non-protein amino acids present in the roots of Panax notoginseng has been found to shorten bleeding time of mice and increase the number of platelets. However, the exact underlying mechanisms have not been elucidated yet. This study was aimed to identify the hemostatic effect of dencichine and uncover its mechanisms. Materials and methods Hemostatic effect was assessed by measuring tail bleeding time and coagulation indices of rats. PT, APTT, TT and FIB concentration were measured using a Sysmex CA-1500 plasma coagulation analyzer. Platelet aggregation rate was determined by using a platelet aggregometer. Concentration of cyotosolic calcium was evaluated by Fluo-3 and levels of cyclic adenosine monophosphate (cAMP) and thromboxane A2 (TXA2) were measured by ELISA method. Results and conclusion Dencichine administered orally shortened tail bleeding time, reduced APTT and TT but increased the concentration of FIB in plasma in a dose-dependent manner. When induced with trap, dencichine could elevate the cytoplasmic concentration of calcium, and secretion of TXA2 as well as the ratio of TXA2 to PGI2 from platelets. Meanwhile, it decreased the level of intracellular cAMP. However, CNQX could block the enhanced hemostatic effect of dencichine. These results suggested that dencichine exerted hemostatic function via AMPA receptors on platelets, therefore, facilitated coagulation cascade in a paracrine fashion by control of platelet cytosolic calcium influx, cAMP production and TXA2 release. Current study may contribute to its clinical use in therapy of hemorrhage.
    Thrombosis Research 05/2014; 133(5). DOI:10.1016/j.thromres.2014.02.009 · 2.43 Impact Factor
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    ABSTRACT: There is no method available to simultaneously detect GABA, Glu, Epi, NE, DA, 5-HT and 5-HIAA in mouse hippocampus. A rapid and sensitive LC-MS/MS method has been developed for simultaneously measuring seven neurotransmitters in mouse hippocampus. The analytes were detected in positive mode with multiple reaction monitoring (MRM) and the procedure was completed in less than 9min. This method exhibited excellent linearity for all of the analytes with regression coefficients higher than 0.99, and showed good intra- and inter-day precisions (RSD<15%) with good accuracy (80-120%). Moreover, the method was successfully applied for the quantitative determination of neurotransmitters in a mouse depression model induced by successive methylprednisolone injections. The results indicated that this depression model was closely associated with the decreased level of Epi (p=0.002) and elevated ratio of 5-HIAA/5-HT (p=0.01), which has never been reported elsewhere. Compared with previous methods, current approach is more convenient without any pre-column derivatization of the analytes but enhances detectability with incremental neurotransmitter profile and shortens detection time. This work represents the first accurate simultaneous determination of seven neurotransmitters in the mouse depression model induced by methylprednisolone. The reliable method will benefit the research of neurological diseases with the altered neurotransmitter profile in brain.
    Journal of neuroscience methods 04/2014; 229. DOI:10.1016/j.jneumeth.2014.04.004 · 1.96 Impact Factor
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    ABSTRACT: 20(S)-Protopanaxadiol (PPD), a dammarane-type triterpenoid sapogenin, acts as the pharmacophore of ginsenosides which are considered as the principal bioactive components in Chinese ginseng. To fully understand the mechanism of action of PPD, it is important to study its metabolic profiles in vivo. Plasma, urine, fece and bile were collected after administration of PPD formulated in 0.5% aqueous Tween-80 to rats (150 mg/kg). Samples were analyzed by using a sensitive and reliable method based on ultra-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS/MS) in both positive and negative ion mode. The chemical structures of metabolites were elucidated by comparing the retention time, accurate molecular mass, and fragmentation patterns of analytes with those of PPD. In total 29 metabolites, including 10 new metabolites (M20-M29), were tentatively identified and characterized. Among them, two metabolites (M3 and M4) were unambiguously identified by matching their retention times and fragmentation patterns with their standards. Principal metabolites, namely, 20, 24-oxide metabolites (M3 and M4), 26/27-carboxylic acid derivatives (M22 and M23) and a glucuronidated product (M28), were found in the rat plasma. The results showed that phase I metabolites are monooxygenation, dioxygenation and oxidative dehydrogenation metabolites, and phase II metabolic pathways were demonstrated to be cysteine conjugation and glucuronidation. The newly identified metabolites are useful to understand the mechanism of elimination of PPD and, in turn, its effectiveness and toxicity. Copyright © 2014 John Wiley & Sons, Ltd.
    Rapid Communications in Mass Spectrometry 03/2014; 28(6):595-604. DOI:10.1002/rcm.6813 · 2.64 Impact Factor
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    ABSTRACT: Pyrrolizidine alkaloids (PAs) are among the most hepatotoxic natural products that produce irreversible injury to humans via consumption of herbal medicine, tea preparation, and honey. Toxicity and death caused by PA exposure have been reported worldwide. Metabolomics and genomics provide scientific and systematic views of living organism, and have become powerful techniques for toxicology research. In this study, senecionine hepatotoxicity on rats was determined via a combination of metabolomic and genomic analyses. From the global analysis generated from two omics data, the compromised bile acid homeostasis in vivo was innovatively demonstrated and confirmed. Serum profiling of bile acids was altered with significantly elevated conjugated bile acids after senecionine exposure, which was in accordance with toxicity. Similarly, the hepatic mRNA levels of several key genes associated with bile acid metabolism were significantly changed. This process included cholesterol 7- hydroxylase, bile acid CoA-amino acid N-acetyltransferase, sodium taurocholate co-transporting polypeptide, organic anion-transporting polypeptides, and multi-drug-resistance-associated protein 3. In conclusion, cross-omics study provides a comprehensive analysis method for studying the toxicity caused by senecionine, which is a hepatotoxic PA. Moreover, the change in bile acid metabolism and the respective transporters may provide a new PA toxicity mechanism.
    Chemical Research in Toxicology 03/2014; 27(5). DOI:10.1021/tx400451q · 4.19 Impact Factor

Publication Stats

535 Citations
215.03 Total Impact Points

Institutions

  • 2006–2015
    • Shanghai University of Traditional Chinese Medicine
      • • Institute of Chinese Materia Medica
      • • Key Laboratory of Standardization of Chinese Medicines of Ministry of Education
      Shanghai, Shanghai Shi, China
  • 2006–2012
    • China Pharmaceutical University
      • Department of Pharmacognosy
      Nan-ching-hsü, Jiangxi Sheng, China