De-An Guo

Chinese Academy of Sciences, Peping, Beijing, China

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Publications (260)585.39 Total impact

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    ABSTRACT: Fangchinoline is a bisbenzylisoquinoline alkaloid isolated from Radix Stephaniae tetrandrae S. Moore. Fangchinoline and its structure analogue, tetrandrine, exhibited direct binding affinity with recombinant human proteasome β1 subunit and also inhibited its activity in vitro. In cultured prostate PC-3 cells and LnCap cells, fangchinoline could dose-dependently inhibit cell proliferation and caspase-like activity of cellular proteasome which was mediated by proteasome β1 subunit. The inhibitive effect of fangchinoline on caspase-like activity of proteasome was also observed in purified human erythrocyte 20S proteasome. In PC-3 cells, fangchinoline induced cell cycle arrest at G0/G1 phase and apoptosis. Treatment of PC-3 tumor-bearing nude mice with fangchinoline inhibited tumor growth, induced apoptosis and also caused decrease in proteasome activities in tumor xenografts. Dose-dependent and time-dependent accumulation of ubiquitinated proteins and important proteasome substrates such as p27, Bax and IκB-α were observed in fangchinoline-treated cells. Over-expression of proteasome β1 subunit by plasmid transfection increased sensitivity of cells to the cytotoxicity of fangchinoline while knockdown of proteasome β1 subunit ameliorated cytotoxicity of fangchinoline in PC-3 cells. Results of the present study suggested that proteasome inhibition was involved in the anti-cancer effects of fangchinoline. Fangchinoline and its structure analogues might be new natural proteasome inhibitors targeting β1 subunit.
    PLoS ONE 10/2015; 10(10):e0141681. DOI:10.1371/journal.pone.0141681 · 3.23 Impact Factor
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    Qi Wang · Xue Qiao · Yi Qian · Zi-Wei Li · Yew-Min Tzeng · De-Min Zhou · De-An Guo · Min Ye ·
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    ABSTRACT: Antrodia cinnamomea is a precious medicinal mushroom. It exhibits promising therapeutic effects on cancer, intoxication, hypertension, hepatitis, and inflammation. Its major bioactive constituents are ergostane and lanostane triterpenoids. In this study, we used intestinal Caco-2 cell monolayer model to reveal the intestinal absorption property of 14 representative triterpenoids from A. cinnamomea. The bidirectional transport through the monolayer at different time points was monitored by a fully validated LC/MS/MS method. In the case of pure compounds, ergostanes 5 (25R-antcin H), 6 (25S-antcin H) and 10 (25R-antcin B) could readily pass through the Caco-2 cell layer, whereas lanostanes 13 (dehydroeburicoic acid) and 14 (eburicoic acid) could hardly pass through. When the cells were treated with A. cinnamomea extract, antcins A, B, C, H and K (1-6 and 9-11) were absorbed via passive transcellular diffusion, and showed high P AB and P BA values (> 2.5 × 10(-5) cm/s). Meanwhile, the lanostanes dehydrosulphurenic acid (8), 15α-acetyldehydrosulphurenic acid (12), 13 and 14 exhibited poor permeability. Transport features of these compounds were consistent with their pharmacokinetic behaviors in rats. This study could also be helpful in predicting the intestinal absorption of A. cinnamomea in human.
    09/2015; DOI:10.1007/s13659-015-0072-4
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    ABSTRACT: Exploration of new natural compounds is of vital significance for drug discovery and development. The conventional approaches by systematic phytochemical isolation are low-efficiency and consume masses of organic solvent. This study presents an integrated strategy that combines offline comprehensive two-dimensional liquid chromatography, hybrid linear ion-trap/Orbitrap mass spectrometry, and NMR analysis (2D LC/LTQ-Orbitrap-MS/NMR), aimed to establish a green protocol for the efficient discovery of new natural molecules. A comprehensive chemical analysis of the total ginsenosides of stems and leaves of Panax ginseng (SLP), a cardiovascular disease medicine, was performed following this strategy. An offline 2D LC system was constructed with an orthogonality of 0.79 and a practical peak capacity of 11,000. The much greener UHPLC separation and LTQ-Orbitrap-MS detection by data-dependent high-energy C-trap dissociation (HCD)/dynamic exclusion were employed for separation and characterization of ginsenosides from thirteen fractionated SLP samples. Consequently, a total of 646 ginsenosides were characterized, and 427 have not been isolated from the genus of Panax L. The ginsenosides identified from SLP exhibited distinct sapogenin diversity and molecular isomerism. NMR analysis was finally employed to verify and offer complementary structural information to MS-oriented characterization. The established 2D LC/LTQ-Orbitrap-MS/NMR approach outperforms the conventional approaches in respect of significantly improved efficiency, much less use of drug materials and organic solvent. The integrated strategy enables a deep investigation on the therapeutic basis of an herbal medicine, and facilitates new compounds discovery in an efficient and environmentally friendly manner as well.
    Analytica chimica acta 09/2015; 893:65-76. DOI:10.1016/j.aca.2015.08.048 · 4.51 Impact Factor
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    ABSTRACT: Malonates are one type of the acylation conjugates and found abundantly in ginseng and soybean. Malonyl conjugates of ginsenosides and isoflavone glycosides were often considered as the characteristic components to evaluate various species and different forms of ginseng and soybean products because of their thermal instability. Another famous isoflavonoid-rich leguminous traditional Chinese medicine (TCM), named Puerarin lobata (Gegen), has also been reported to contain malonyl daidzin and malonyl genistin. However, the conjugates were found to present in very low amount and particularly unstable in the negative ion mode scan using LTQ Orbitrap mass spectrometry with electrospray ionization (ESI). In order to screen and characterize the malonyl conjugates in Gegen, a specific method was designed and developed combining neutral loss ion mapping (NLIM) experiment and precursor mass list (PL) triggered data dependent acquisition (DDA). Along with the activation of dynamic exclusion (DE), the method was proven to be specific and efficient for searching the malonate derivatives from Gegen. Two samples were examined by the established method. A total of 66 compounds were found, and 43 of them were malonates of isoflavone glycoside. Very few compounds were reported previously in Gegen. The results are helpful to understand the constituents of Gegen with more insight. The study not only provided a method for analyzing the malonyl conjugates from complex matrices but also explored a way to trace other low amount components in TCMs. Graphical Abstract ᅟ.
    Journal of the American Society for Mass Spectrometry 09/2015; DOI:10.1007/s13361-015-1240-9 · 2.95 Impact Factor
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    ABSTRACT: Kansui radix (KR) is a poisonous Chinese herbal medicine recorded in the Chinese Pharmacopoeia, and the acute toxicity obstructs its clinical applications. To explore its acute toxicity mechanism to enhance clinical safety, a metabolomics study based on UPLC-ESI-QTOF-MS(E) was performed. Wistar rats were exposed for 4h to the aqueous and ethyl acetate extracts prepared from KR at a high dose (25g/kg). The contents of six different sections of rat intestine, including the duodenum, jejunum, ileum, cecum, colon, and rectum were collected as samples for the first time, as well as the rat plasma. The interesting results showed that only those rats exposed to the ethyl acetate extract showed a watery diarrhea, similar to the observed acute human toxicity. The identified biomarkers found in the plasma, such as phenol sulfate, indoxyl sulfate, and p-cresol sulfate were significantly perturbed in the rats. These biomarkers are known as colon-derived uremic compounds, which were first reported with respect to KR. The three essential amino acids which produced these biomarkers were only found in the contents of colon and rectum. A hypothesis was proposed that only the colon-derived uremic compounds induced by KR might be responsible for the acute toxicity. Three traditional process methods to reduce the toxicity of KR were compared based on these biomarkers, and different levels of toxicity modulation were observed. These results may be helpful to further understand the mechanism of acute toxicity, and the relevance of the traditional process methods to ameliorate the adverse effects of KR.
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 09/2015; DOI:10.1016/j.jchromb.2015.09.022 · 2.73 Impact Factor
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    ABSTRACT: Licorice (Glycyrrhiza uralensis Fisch.) is one of the most popular herbal medicines worldwide. This study aims to identify the metabolites of seven representative bioactive licorice compounds in rats. These compounds include 22β-acetoxyl glycyrrhizin (1), licoflavonol (2), licoricidin (3), licoisoflavanone (4), isoglycycoumarin (5), semilicoisoflavone B (6), and 3-methoxy-9-hydroxy-pterocarpan (7). After oral administration of 250mg/kg of 1 or 40mg/kg of 2-7 to rats, a total of 16, 43 and 31 metabolites were detected in the plasma, urine and fecal samples, respectively. The metabolites were characterized by HPLC/DAD/ESI-MS(n) and LC/IT-TOF-MS analyses. Particularly, two metabolites of 1 were unambiguously identified by comparing with reference standards, and 22β-acetoxyl glycyrrhizin-6″-methyl ester (1-M2) is a new compound. Compound 1 could be readily hydrolyzed to eliminate the glucuronic acid residue. The phenolic compounds (4-7) mainly undertook phase II metabolism (glucuronidation or sulfation). Most phenolic compounds with an isoprenyl group (chain or cyclized, 2-5) could also undertake hydroxylation reaction. This is the first study on in vivo metabolism of these licorice compounds. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of pharmaceutical and biomedical analysis 08/2015; 115:515-522. DOI:10.1016/j.jpba.2015.08.013 · 2.98 Impact Factor
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    ABSTRACT: Lack of pharmacological strategies in clinics restricts the patient prognosis with myocardial ischemia/reperfusion (I/R) injury. The aim of this study was to evaluate the cardioprotection of combined salvianolic acid B (SalB) and ginsenoside Rg1 (Rg1) against myocardial I/R injury and further investigate the underlying mechanism. I/R injury was induced by coronary artery ligation for Wistar male rats and hypoxia/reoxygenation injury was induced on H9c2 cells. Firstly, the best ratio between SalB and Rg1was set as 2:5 based on their effects on heart function detected by hemodynamic measurement. Then SalB-Rg1 (2:5) was found to maintain mitochondrial membrane potential and resist apoptosis and necrosis in H9c2 cell with hypoxia/reoxygenation injury. Companying with same dose of SalB or Rg1 only, SalB-Rg1 showed more significant effects on down-regulation of myocardial infarct size, maintenance of myocardium structure, improvement on cardiac function, decrease of cytokine secretion including TNF-α, IL-1β, RANTES and sVCAM-1. Finally, the SalB-Rg1 improved the viability of cardiac myocytes other than cardiac fibroblasts in rats with I/R injury using flow cytometry. Our results revealed that SalB-Rg1 was a promising strategy to prevent myocardial I/R injury.
    PLoS ONE 08/2015; 10(8):e0135435. DOI:10.1371/journal.pone.0135435 · 3.23 Impact Factor
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    ABSTRACT: Curcumin is the major constituent of turmeric (Curcuma longa L.). It has attracted widespread attention for its anticancer and anti-inflammatory activities. The separation of curcumin and its two close analogues, demethoxycurcumin and bisdemethoxycurcumin, has been challenging by conventional techniques. In this paper, an environmentally friendly method based on supercritical fluid chromatography was established for rapid and facile separation of the three curcuminoids directly from the methanol extract of turmeric. The method was firstly developed and optimized by ultra performance convergence chromatography, and was then scaled up to preparative supercritical fluid chromatography. Eluted with supercritical fluid CO2 containing 8-15% methanol (containing 10 mM oxalic acid) at a flow rate of 80 mL/min, curcumin, demethoxycurcumin and bisdemethoxycurcumin could be well separated on a Viridis BEH OBD column (Waters, 250 mm × 19 mm, 5 μm) within 6.5 min. As a result, 20.8 mg of curcumin (97.9% purity), 7.0 mg of demethoxycurcumin (91.1%), and 4.6 mg of bisdemethoxycurcumin (94.8%) were obtained after a single step of supercritical fluid chromatography separation with a mean recovery of 76.6%. Showing obvious advantages in low solvent consumption, large sample loading, and easy solvent removal, supercritical fluid chromatography was proved to be a superior technique for the efficient separation of natural products. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Separation Science 08/2015; 38(19). DOI:10.1002/jssc.201500686 · 2.74 Impact Factor
  • Min Yang · Zhe Zhou · De-an Guo ·
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    ABSTRACT: Sulfurous compounds are commonly present in plants, fungi, and animals. Most of them were reported to possess various bioactivities. Isotopic pattern filter (IPF) is a powerful tool for screening compounds with distinct isotope pattern. Over the past decades, the IPF was used mainly to study Cl- and Br-containing compounds. To our knowledge, the algorithm was scarcely used to screen S-containing compounds, especially when combined with chromatography analyses, because the 34S isotopic ion is drastically affected by 13C2 and 18O. Thus, we present a new method for a fine isotopic pattern filter (FIPF) based on the separated M + 2 ions (12Cx1Hy16Oz32S13C218O, 12Cx+21Hy16Oz+134S, tentatively named M + 2OC and M + 2S) with an ultra-high-resolution mass (100,000 FWHM @ 400 m/z) to screen sulfur derivatives in traditional Chinese medicines (TCM).This finer algorithm operates through convenient filters, including an accurate mass shift of M + 2OC and M + 2S from M and their relative intensity compared to M. The method was validated at various mass resolutions, mass accuracies, and screening thresholds of flexible elemental compositions. Using the established FIPF method, twelve S-derivatives were found in the popular medicinal used Pueraria species, and 9 of them were tentatively identified by high-resolution multiple stage mass spectrometry (HRMSn). The compounds were used to evaluate the sulfurous compounds' situation in commercially purchased Pueraria products. The strategy presented here provides a promising application of the IPF method in a new field.
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    ABSTRACT: Alstonia scholaris has been used in "Dai" ethnic medicine to treat chronic respiratory diseases for a long history, and the major bioactive constituents are alkaloids. An alkaloidal extract of A. scholaris leaves (AAS) has been developed into an investigational new drug, and has been approved for phase I/II clinical trials by China Food and Drug Administration. However, little is known on the chemical composition and in vivo metabolism of AAS, thus far. In this study, an ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC/qTOF-MS) method was established to characterize the chemical constituents of AAS. Samples were separated on an ACQUITY UPLC CSH column (2.1×100mm, 1.7μm) with acetonitrile and water containing 0.3% formic acid as the mobile phase. On the basis of high-accuracy mass spectral analysis, a total of 35 alkaloids were characterized from AAS, including 11 scholaricine-type, 9 vallesamine-type, 12 picrinine-type, and 3 tubotaiwine-type alkaloids. Furthermore, the metabolic pathways of 4 representative alkaloids in rats were studied. They mainly undertook hydroxylation and glucuronidation reactions. Based on the above metabolic pathways, the metabolism of AAS (10mg/kg) in rats after oral administration was studied by LC/MS. A total of 33 compounds in plasma, 40 compounds in urine, and 38 compounds in feces were characterized. The results indicated that scholaricine-type alkaloids could get into circulation more readily than the other types. This is the first systematic study on chemical profiling and metabolites identification of AAS. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 07/2015; DOI:10.1016/j.jchromb.2015.07.044 · 2.73 Impact Factor
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    ABSTRACT: An efficient and target-oriented sample enrichment method was established to increase the content of the minor alkaloids in crude extract by using the corresponding two-phase solvent system applied in pH-zone-refining counter-current chromatography. The enrichment and separation of seven minor indole alkaloids from Uncaria rhynchophylla (Miq.) Miq. ex Havil(UR) were selected as an example to show the advantage of this method. An optimized two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (3:7:1:9, v/v) was used in this study, where triethylamine (TEA) as the retainer and hydrochloric acid (HCl) as the eluter were added at the equimolar of 10mM. Crude alkaloids of UR dissolved in the corresponding upper phase (containing 10mM TEA) were extracted twice with lower phase (containing 10mM TEA) and lower phase (containing 10mM HCl), respectively, the second lower phase extract was subjected to pH-zone-refining CCC separation after alkalization and desalination. Finally, from 10g of crude alkaloids, 4g of refined alkaloids was obtained and the total content of seven target indole alkaloids was increased from 4.64% to 15.78%. Seven indole alkaloids, including 54mg isocorynoxeine, 21mg corynoxeine, 46mg isorhynchophylline, 35mg rhynchophylline, 65mg hirsutine, 51mg hirsuteine and 27mg geissoschizine methylether were all simultaneously separated from 2.5g of refined alkaloids, with the purity of 86.4%, 97.5%, 90.3%, 92.1%, 98.5%, 92.3%, and 92.8%, respectively. The total content and purities of the seven minor indole alkaloids were tested by HPLC and their chemical structures were elucidated by ESI-HRMS and (1)H NMR. Copyright © 2015. Published by Elsevier B.V.
    Journal of Chromatography A 07/2015; 1409. DOI:10.1016/j.chroma.2015.07.066 · 4.17 Impact Factor
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    ABSTRACT: Despite the numerous pharmacological agents available for hypertension therapy, hypertension-related microvascular remodeling is not resolved, eventually leading to end-organ damage. The aim of the present study was to investigate the protection of salvianolic acid A (SalA) against microvascular remodeling in vitro and in vivo. Spontaneously hypertensive rats (SHR) were administered 2.5, 5 or 10 mg/kg SalA via intraperitoneal injection once a day for 4 weeks. The tail-cuff method was applied to monitor blood pressure; the microvascular structure of retina was detected by hematoxylin-eosin and immunohistochemical staining; the function of mesenteric arteries was measured by DMT wire myography; endothelial cell proliferation was estimated using Cell Counting Kit 8; endothelial cell migration was evaluated by wound healing and transwell assay; and endothelial cell integrity was detected by transendothelial electrical resistance and permeability assays. Although no antihypertensive effects of SalA were observed, SalA attenuated the microvascular inward remodeling of the retina and improved microvascular function in the mesenteries in vivo. Further cell experiments confirmed the beneficial effects of SalA on the integrity of the endothelial monolayer in vitro. Salvianolic acid A inhibited endothelial dysfunction and vascular remodeling in spontaneously hypertensive rats. Therefore, salvianolic acid A could be a potential drug therapy to prevent further targeted organ damage induced by vascular remodeling. Copyright © 2015. Published by Elsevier Inc.
    Life sciences 06/2015; DOI:10.1016/j.lfs.2015.06.010 · 2.70 Impact Factor
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    ABSTRACT: Current China Pharmacopoeia (ChP) standards employ diversified and case-dependent assay methods to evaluate the quality of different Chinese patent medicines (CPMs) that contain Panax notoginseng as the monarch drug. These conventional, HPLC-based approaches, utilizing a complex sample preparation procedure, can easily result in low analytical efficiency and possible component loss. Here, a "monomethod-heterotrait matrix" (MHM) strategy is proposed, that is, developing a universal multi heart-cutting two-dimensional liquid chromatography (MHC-2D-LC) approach that facilitates the simultaneous quantitation of five P. notoginseng saponins (noto-R1, Re, Rg1, Rb1, and Rd) in eight different CPMs. The MHC-2D-LC system was constructed on a dual-gradient liquid chromatography instrument equipped with a Poroshell SB C18 column and a Zorbax SB-Aq column for respective (1)D and (2)D separation. Method validation was performed in terms of specificity, linearity (r(2) and F-test), intra-/inter-day precision (0.4-7.9%), stability (1.2-3.9%), and recovery (90.2-108.7%), and the LODs and LOQs (loaded masses) of the five analytes varied between 4.0-11.0ng and 6.0-33.0ng, respectively. The validated MHC-2D-LC approach was subsequently applied to quantify the five saponins in thirty batches of different CPMs. The method demonstrated superiority over the current ChP assay methods in respect of specificity (avoiding co-elution), resolution (Rs>1.5), sample preparation (easy-to-implement ultrasonic extraction without repeated re-extraction), and transfer rate (minimum component loss). This is the first application of an MHC-2D-LC method for the quantitative assessment of the constituents of CPMs. The MHM approach represents a new, strategically significant methodology for the quality control of CPMs that involve complex chemical matrix. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of Chromatography A 05/2015; 1402. DOI:10.1016/j.chroma.2015.05.015 · 4.17 Impact Factor
  • Hu Chen · Yu-Hui Meng · De-An Guo · Xuan Liu · Jun-Hua Liu · Li-Hong Hu ·
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    ABSTRACT: One new 19-norbufadienolide (1) and one new bufogargarizin (2), together with twelve known bufadienolides (3-14, resp.) were isolated from Chan Su, a traditional Chinese medicine that is used in the treatment of cancer. Their structures were elucidated on the basis of detailed spectroscopic analysis and comparison of corresponding data that is previously reported. The cytotoxic activities of the isolated compounds were evaluated on HeLa and A549 cell lines. Though 1 and 2 showed weak cytotoxic activities on both cell lines, compounds 4 and 5 showed lower IC50 values than bufalin, the most widely studied bufadienolide in Chan Su. Furthermore, four 3-ester derivatives (15-18) of compound 4 were synthesized and their cytotoxic activities were also evaluated. Analysis of the structure-activity relationship indicated that bufadienolides with aldehyde group at C-10 or α-hydroxyl group at C-11 exhibit stronger cytotoxic activities on both cell lines. The cytotoxic activity of arenobufagin-3-ester derivative 17 was 4-fold higher than compound 4. Copyright © 2015. Published by Elsevier B.V.
    Fitoterapia 05/2015; 104:1-6. DOI:10.1016/j.fitote.2015.05.011 · 2.35 Impact Factor
  • Xue Qiao · Wei Song · Shuai Ji · Qi Wang · De-an Guo · Min Ye ·
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    ABSTRACT: Licorice is one of the most popular herbal medicines worldwide. It contains a big array of phenolic compounds (flavonoids, coumarins, and diphenylethanones). Due to high structural diversity, low abundance, and co-elution with licorice saponins, these phenolic compounds are difficult to be separated by conventional chromatography. In this study, a mobile phase-dependent reversed-phase×reversed phase comprehensive two-dimensional liquid chromatography (RP×RP 2DLC) method was established to separate phenolic compounds in licorice (the roots of Glycyrrhiza uralensis). Organic solvents in the mobile phase were optimized to improve orthogonality of the first and second dimensions, and a synchronized gradient mode was used to improve chromatographic resolution. Finally, licorice extracts were eluted with methanol/water/formic acid in the first dimension (Acquity CSH C18 column), and acetonitrile/water/formic acid in the second dimension (Poroshell Phenyl-Hexyl column). By using this 2DLC system, a total of 311 compounds were detected within 40min. The practical and effective peak capacity was 1329 and 524, respectively, and the orthogonality was 79.8%. The structures of 21 selected unknown compounds were tentatively characterized by mass spectrometry, and 8 of them were discovered from G. uralensis for the first time. The mobile phase-dependent 2DLC/MS system could benefit the separation and characterization of natural products in complicated herbal extracts. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of Chromatography A 05/2015; 1402. DOI:10.1016/j.chroma.2015.05.006 · 4.17 Impact Factor
  • Wangping Deng · Tongtong Xu · Min Yang · Yajun Cui · De-An Guo ·
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    ABSTRACT: A high performance liquid chromatographic (HPLC) fingerprint is commonly used for quality consistency evaluation of herbal medicines. Recently, an improved chromatographic technique resulted in ultra high performance liquid chromatography (UHPLC), which could provide higher resolution in less time under higher pressure using finer particles (less than 2μm) of stationary phase. A simple and sensitive method was developed and validated for fingerprint analysis of Penthorum chinense Pursh (PC), with the simultaneous determination of seven components using UPLC coupled with a diode-array detector (DAD). It took less than 20 min for analysis of one sample. Both similarity analysis and principle components analysis (PCA) were employed to evaluate the quality consistency of 17 sample batches. The analysis was performed on a Waters ACQUITY UPLC HSS T3 (2.1 x 150 mm, 1.7 μm) column, which was maintained at 45°C and the eluents were monitored with DAD at 270 nm. A gradient elution with acetonitrile and water containing 0.075% phosphoric acid was used. The solvent flow rate was 0.4 mL/min. Standard calibration curves showed good linear behavior (R2 > 0.9994) in the range of 0.20-337.05 μg/mL. Acceptable repeatability (RSD < 0.61%), reproducibility (RSD < 2.72%), stability (RSD < 1.59%) and recovery in the range of 94.7%-102.9% were obtained (precision and accuracy). The validated method was successfully applied to evaluate the quality of 21 samples of PC.
    Natural product communications 04/2015; 10(1):71-6. · 0.91 Impact Factor
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    ABSTRACT: Antrodia cinnamomea is a precious medicinal mushroom popularly used for adjuvant cancer therapy in Taiwan. Its major bioactive constituents are ergostane and lanostane triterpenoids. Although clinical trials for A. cinnamomea have been recently initiated, its metabolism remains unclear. The present study aims to elucidate the metabolism and pharmacokinetics of A. cinnamomea in rats. After oral administration of an ethanol extract, 18 triterpenoids and 8 biotransformed metabolites were detected in rats plasma by UHPLC/qTOF-MS. Four of the metabolites were prepared by semi-synthesis and fully identified by NMR, while the others were tentatively characterized by comparing with the metabolites of single compounds (antcins B, C, H and K). Furthermore, a multi-component pharmacokinetic study of A. cinnamomea was carried out to monitor the plasma concentrations of 14 triterpenoids (ergostanes 1-3, 5-8, 14-16; lanostanes 9, 10, 17, 19) and 2 metabolites (M5, M6) by LC/MS/MS in rats after oral administration of the ethanol extract (1.0g/kg). The results showed that ergostanes and Δ(7,9(11)) lanostanes, but not Δ(8) lanostanes, could get into circulation. The low-polarity ergostanes (antcins B and C) undertook hydrogenation (C-3 or C-7 carbonyl groups) or hydroxylation to produce polar metabolites. High-polarity ergostanes (antcins H and K) and Δ(7,9(11)) lanostanes were metabolically stable. We also discovered that ergostanes and lanostanes showed remarkably different pharmacokinetic patterns. The ergostanes were generally absorbed and eliminated rapidly, whereas the lanostanes remained in the plasma at a low concentration for a relatively long time. The results indicate that high-polarity ergostanes are the major plasma-exposed components of A. cinnamomea, and may play an important role in its therapeutic effects. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of pharmaceutical and biomedical analysis 04/2015; 111:266-276. DOI:10.1016/j.jpba.2015.04.010 · 2.98 Impact Factor
  • Qi Wang · Xue Qiao · Yi Qian · Chun-fang Liu · Yan-fang Yang · Shuai Ji · Jun Li · De-an Guo · Min Ye ·
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    ABSTRACT: Coumarins are an important group of bioactive constituents in licorice (Glycyrrhiza uralensis), a worldwide popular herbal medicine. This study aims to elucidate the metabolism of two major licorice coumarins, glycyrin and glycyrol in rats. After oral administration of 40 mg/kg glycyrin, neither the parent compound nor its metabolites could be detected in rats plasma or urine samples, indicating that glycyrin had poor oral bioavailability. Two hydroxylated metabolites, 4″-hydroxyl glycyrin and 5″-hydroxyl glycyrin, were detected in rat liver microsome incubation system. Among them, the major metabolite 4″-hydroxyl glycyrin, which is a new compound, was obtained by microbial transformation of Syncephalastrum racemosum AS 3.264. Its structure was fully identified by 1D and 2D NMR. Meanwhile, glycyrol, together with three metabolites, were detected in rats urine and fecal samples after oral administration (40 mg/kg). Their structures were tentatively characterized by LC/MS. Glycyrol mainly undertakes hydroxylation metabolism, accompanied by hydration and dehydrogenation as minor reactions. This is the first systematic study on metabolism of glycyrin and glycyrol. The results could be valuable to evaluate druggability of these bioactive natural products.
    Journal of Chromatography B 03/2015; 983. DOI:10.1016/j.jchromb.2014.12.028 · 2.73 Impact Factor
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    ABSTRACT: Coumarinlignan (1), possessing a unique coumarin-containing lignan skeleton, was isolated from the stems of Kadsura heteroclita. Its structure and absolute configuration were determined by spectroscopic techniques, especially 2D NMR and X-ray crystallographic data analyses. The proposed biosynthetic pathway is discussed. This new compound showed good anti-HBV activity against HBeAg and HBsAg, and moderate anti-fibrotic and neuroprotective activities. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Bioorganic & Medicinal Chemistry Letters 02/2015; 25(7). DOI:10.1016/j.bmcl.2015.02.022 · 2.42 Impact Factor
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    ABSTRACT: Gambogic acid (GA) is an anticancer agent in phase ‖b clinical trial in China but its mechanism of action has not been fully clarified. The present study was designed to search the possible target-related proteins of GA in cancer cells using proteomic method and establish possible network using bioinformatic analysis. Cytotoxicity and anti-migration effects of GA in MDA-MB-231 cells were checked using MTT assay, flow cytometry, wound migration assay, and chamber migration assay. Possible target-related proteins of GA at early (3 h) and late stage (24 h) of treatment were searched using a proteomic technology, two-dimensional electrophoresis (2-DE). The possible network of GA was established using bioinformatic analysis. The intracellular expression levels of vimentin, keratin 18, and calumenin were determined using Western blotting. GA inhibited cell proliferation and induced cell cycle arrest at G2/M phase and apoptosis in MDA-MB-231 cells. Additionally, GA exhibited anti-migration effects at non-toxic doses. In 2-DE analysis, totally 23 possible GA targeted proteins were found, including those with functions in cytoskeleton and transport, regulation of redox state, metabolism, ubiquitin-proteasome system, transcription and translation, protein transport and modification, and cytokine. Network analysis of these proteins suggested that cytoskeleton-related proteins might play important roles in the effects of GA. Results of Western blotting confirmed the cleavage of vimentin, increase in keratin 18, and decrease in calumenin levels in GA-treated cells. In summary, GA is a multi-target compound and its anti-cancer effects may be based on several target-related proteins such as cytoskeleton-related proteins. Copyright © 2015 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.
    Chinese Journal of Natural Medicines 01/2015; 13(1):41-51. DOI:10.1016/S1875-5364(15)60005-X · 1.11 Impact Factor

Publication Stats

4k Citations
585.39 Total Impact Points


  • 2007-2015
    • Chinese Academy of Sciences
      • Research Center for Modernization of Traditional Chinese Medicine
      Peping, Beijing, China
  • 2002-2015
    • Peking University
      • • State Key Laboratory of Natural and Biomimetic Drugs
      • • School of Pharmaceutical Sciences
      • • Modern Research Center for Traditional Chinese Medicine
      Peping, Beijing, China
  • 2006-2014
    • Shanghai Institutes for Biological Sciences
      Shanghai, Shanghai Shi, China
  • 2009-2013
    • Shenyang Pharmaceutical University
      • • Department of Pharmacy
      • • College of Traditional Chinese Materia Medica
      Feng-t’ien, Liaoning, China
  • 2008-2013
    • China Pharmaceutical University
      • College of Traditional Chinese Medicine
      Nan-ching-hsü, Jiangxi Sheng, China
  • 2012
    • China Academy of Traditional Chinese Medicine
      Peping, Beijing, China
    • Shanghai Research Institute of Materials
      Shanghai, Shanghai Shi, China
  • 2007-2011
    • Peking University Health Science Center
      Peping, Beijing, China