Publications by authors named "Mingcang Chen"

36 Publications

Baicalin Inhibits Influenza A Virus Infection Promotion of M1 Macrophage Polarization.

Front Pharmacol 2020 6;11:01298. Epub 2020 Oct 6.

Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, Fudan University School of Pharmacy, Shanghai, China.

Background And Aims: The natural compound baicalin (BA) possesses potent antiviral properties against the influenza virus. However, the underlying molecular mechanisms of this antiviral activity and whether macrophages are involved remain unclear. In this study, we, therefore, investigated the effect of BA on macrophages.

Methods: We studied macrophage recruitment, functional phenotypes (M1/M2), and the cellular metabolism flow cytometry, qRT-PCR, immunofluorescence, a cell culture transwell system, and GC-MS-based metabolomics both in H1N1 A virus-infected mice and .

Results: BA treatment drastically reduced macrophage recruitment (CD11b, F4/80) by approximately 90% while maintaining the proportion of M1-polarized macrophages in the bronchoalveolar lavage fluid of infected mice. This BA-stimulated macrophage M1 phenotype shift was further verified in ANA-1 and primary peritoneal macrophages by measuring macrophage M1 polarization signals (CD86, iNOS, TNF-α, ratio, and IL-1β cleavage). Meanwhile, we observed an activation of the IFN pathway (upregulation of and ), an inhibition of influenza virus replication (as measured by the gene), and distinct cellular metabolic responses in BA-treated cells.

Conclusion: BA triggered macrophage M1 polarization, IFN activation, and other cellular reactions, which are beneficial for inhibition of H1N1 A virus infection.
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http://dx.doi.org/10.3389/fphar.2020.01298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574031PMC
October 2020

Determination of the antidiabetic chemical basis of Phellodendri Chinensis Cortex by integrating hepatic disposition in vivo and hepatic gluconeogenese inhibition in vitro.

J Ethnopharmacol 2020 Dec 5;263:113215. Epub 2020 Aug 5.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

Ethnopharmacological Relevance: Phellodendri Chinensis Cortex (PCC) has been an herb clinically used to treat diabetes, but the chemical basis of its antidiabetic effects has remained unclear.

Aim Of This Study: Based on the efficacy of herbal medicine resulting from the cooperative response of the effective compounds in the target organs with sufficient exposure, the in vivo hepatic disposition and in vitro hepatic gluconeogenesis inhibition were integrated to elucidate the chemical basis for the antidiabetic effect of orally administered PCC from a target organ, liver, perspective.

Materials And Methods: With a developed and validated HPLC-MS/MS method, three alkaloids and five metabolites were determined in the portal vein plasma, liver, and systemic plasma of rats orally administered PCC. The inhibition of hepatic gluconeogenesis by the eight compounds was evaluated in primary hepatocytes.

Results: The in vivo results showed that magnoflorine was present at the highest concentration among the target constituents in the plasma, where berberine showed a low concentration. In contrast, berberine showed the highest concentration in the liver, and its five metabolites exhibited substantial hepatic accumulation. This discrepancy was strongly associated with the hepatic disposition of the compounds. The hepatic disposition prevented the transfer of 96.1% of the phellodendrine, 71.1% of the berberine and 47.5% of the magnoflorine from the portal vein plasma to the systemic plasma, which corresponded to their hepatic distribution and hepatic metabolism. In vitro, berberine, M1, M4 and M5 significantly and dose-dependently inhibited hepatic glucose production. By integrating the hepatic exposure and inhibitory activity data, we estimated that berberine contributed the most (74%) to the total glucose production inhibition of the orally administered PCC decoction, followed by M4 (14%), M1 (11%) and M5 (1%).

Conclusion: This study was the first to comprehensively describe the pharmacokinetic profiles and hepatic disposition of alkaloids in PCC, and concluded that berberine and its metabolites contributed the most to the total hepatic gluconeogenesis inhibition by orally administered PCC. These results reveal the chemical basis for the antidiabetic effect of orally administered PCC decoction, providing scientific evidence to support the clinical usage of PCC in diabetes treatment.
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http://dx.doi.org/10.1016/j.jep.2020.113215DOI Listing
December 2020

Correction to: Identifying the active components of Baihe-Zhimu decoction that ameliorate depressive disease by an effective integrated strategy: a systemic pharmacokinetics study combined with classical depression model tests.

Chin Med 2020;15:32. Epub 2020 Apr 2.

2Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203 People's Republic of China.

[This corrects the article DOI: 10.1186/s13020-019-0254-9.].
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http://dx.doi.org/10.1186/s13020-020-00312-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115082PMC
April 2020

Identifying the active components of Baihe-Zhimu decoction that ameliorate depressive disease by an effective integrated strategy: a systemic pharmacokinetics study combined with classical depression model tests.

Chin Med 2019 24;14:37. Epub 2019 Sep 24.

2Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Science, Shanghai, 201203 People's Republic of China.

Background: Modern pharmacological studies have demonstrated that Baihe-Zhimu decoction (BZD) has antidepressant effects. However, the complex composition and lack of clear evaluation standards for BZD make it less likely to be understood and accepted than evidence-based active natural compounds.

Methods: In this study, an effective method for the identification of antidepressant components was demonstrated and applied to BZD. The first step was to evaluate the efficacy of BZD by the forced swimming test (FST) and the tail suspension test (TST), followed by successive quantitative analyses of the absorbed constituents at different stages, such as before hepatic disposition, liver distribution, after hepatic disposition and brain distribution after the oral administration of BZD. Finally, the compounds detected in the brain were confirmed by activity testing.

Results: Our investigation observed that timosaponin BII and timosaponin BIII were accurately determined in the brain after oral administration of BZD, and they were further confirmed to reduce the immobility time in the FST and TST. As described above, timosaponin BII and timosaponin BIII were used to scientifically and reasonably explain the effective chemical basis of the effect of BZD on depression.

Conclusions: This research affords an effective method to discover lead molecules for antidepressants from traditional Chinese medicine.
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http://dx.doi.org/10.1186/s13020-019-0254-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6757420PMC
September 2019

A comprehensive study of pomegranate flowers polyphenols and metabolites in rat biological samples by high-performance liquid chromatography quadrupole time-of-flight mass spectrometry.

J Chromatogr A 2019 Oct 22;1604:460472. Epub 2019 Aug 22.

University of Chinese Academy of Sciences, Beijing 100049, China; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address:

Pomegranate flowers is an ancient medicine that has commonly been used to treat various diseases such as diabetes. However, no reports are available on the metabolic profile of pomegranate flowers in vivo. In the present study, with the aid of HPLC-Q-TOF-MS, 67 compounds were identified in pomegranate flowers extract, including 18 ellagitannins, 14 gallic acid and galloyl derivatives, five anthocyanins and 18 flavonoids. Seven compounds were firstly identified. In vivo, 22 absorbed compounds and 35 metabolites were identified in rat biosamples (urine, feces, plasma and tissues) after orally administered with pomegranate flowers extract. This result showed that not all compounds abundant in pomegranate flowers extract could be absorbed well in plasma and tissues. This finding also suggested a potential correlation between study on metabolic profile of these compounds in vivo and study on strategy of screening bioactivity of the isolates with in vitro cell systems evaluation. Notably, mono-glucuronide conjugated metabolite of ellagitannin compound (corilagin) was firstly identified. In addition, this is first report to identify phase II conjugate metabolites of ellagitannins in vivo after oral administration of ellagitannins-rich extracts (or foods). Thus, characterizing its multiple constitution, absorption and metabolic fate of these compounds in vivo is helpful to better analyze the active components in pomegranate flowers.
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http://dx.doi.org/10.1016/j.chroma.2019.460472DOI Listing
October 2019

Determining the protective effects of Yin-Chen-Hao Tang against acute liver injury induced by carbon tetrachloride using 16S rRNA gene sequencing and LC/MS-based metabolomics.

J Pharm Biomed Anal 2019 Sep 21;174:567-577. Epub 2019 Jun 21.

Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Material Medica, Chinese Academy of Science, Shanghai, 201203, PR China. Electronic address:

Yin-Chen-Hao Tang (YCHT), consisting of Artemisia annua L., Gardenia jasminoides Ellis, and Rheum Palmatum L., has been used to relieve liver diseases in China for thousands of years. Several protective mechanisms of YCHT on liver injury have been investigated based on metabolomics, but the effects of YCHT on the alterations in the gut microbiota are still unclear. In this study, an integrated approach based on 16S rRNA gene sequencing combined with high-performance liquid chromatography-mass spectrometry (HPLC-MS) metabolic profiling was performed to assess the effects of YCHT on liver injury induced by carbon tetrachloride (CCl) through the regulation of the relative abundances of gut microbiota and their relationships with biomarker candidates. A total of twelve significantly altered bacterial genera and nine metabolites were identified, which returned to normal levels after YCHT treatment. The relative abundances of the identified microbiota, including significantly elevated amounts of p_Firmicutes, c_Clostridia, o_Clostridiales, f_Ruminococcaceae, g_[Eubacterium]_coprostanoligenes_group, s_uncultured_bacterium_f_Lachnospiraceae and remarkedly increased amounts of p_Bacteroidetes, c_Bacteroidia, o_Bacteroidales, f_Bacteroidaceae, g_Bacteroides and s_uncultured_bacterium_g_Bacteroides, were found in model rats compared with controls. Potential biomarkers, including lower levels of LysoPC (16:1(9Z)/0:0), LysoPC (20:3(5Z,8Z,11Z)), LysoPC (17:0), LysoPC (20:1(11Z)) and 3-hydroxybutyric acid and higher amounts of ornithine, L-kynurenine, hippuric acid and taurocholic acid are involved in several custom metabolic pathways, such as arginine and proline metabolism, tryptophan metabolism, glycerophospholipid metabolism and primary bile acid biosynthesis. Interestingly, there was a strong correlation between the perturbed gut microbiota in genera c_Clostridia and o_Clostridiales and the altered plasma metabolite 3-hydroxybutyric acid. This finding means that the hepatoprotective effects of YCHT may be due to the regulation of the production of the functional metabolite 3-hydroxybutyric acid through changes in the proportions of c_Clostridia and o_Clostridiales. These results showed that the hepatoprotective effects of YCHT not only focused on custom metabolic pathways but also depended on the changes in the gut microbiota in liver injury. These findings suggest that the 16S rRNA gene sequencing and LC-MS based metabolomics approach can be applied to comprehensively evaluate the effects of traditional Chinese medicines (TCMs).
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http://dx.doi.org/10.1016/j.jpba.2019.06.028DOI Listing
September 2019

Metabonomics Study on the Hepatoprotective Effect of Leaf Saponins Using UPLC/Q-TOF-MS Analysis.

Am J Chin Med 2019 23;47(3):559-575. Epub 2019 Apr 23.

* Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Material Medica, Chinese Academy of Science, Shanghai Zhangjiang Hitech Park, Shanghai 201203, P. R. China.

Alcohol liver disease is a major public health problem associated with lifestyle. Our recent study demonstrated that the roots of saponins (PNS) exert hepatoprotective effects against alcohol consumption. Considering that the leaves of saponins (LPNS) have similar chemical ingredients with PNS, increased attention should be given to the hepatoprotective effects of LPNS. In this study, a metabonomic approach based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) was developed to evaluate the hepatoprotective effect of LPNS on alcoholic fatty liver and elucidate the interaction mechanisms. Results showed that the ethanol-induced metabolic perturbations were restored after treatment with LPNS. Furthermore, 12 potential biomarkers (11 upregulated and 1 downregulated) were identified by V-plot and orthogonal partial least square discriminant analysis. Changes in the levels of these metabolites indicated that glycerophospholipid and fatty acid metabolism were disturbed in alcoholic fatty liver mouse. Our findings demonstrated that the UHPLC-QTOF/MS-based metabonomic method may provide a useful means for exploring biomarkers involved in alcoholic fatty liver and elucidating the therapeutic effects of LPNS. This work also showed that the metabonomic approach is a powerful and promising tool for the evaluation of the efficacy of traditional Chinese medicine and elucidation of related mechanisms.
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http://dx.doi.org/10.1142/S0192415X19500290DOI Listing
October 2019

Exploration of the hepatoprotective chemical base of an orally administered herbal formulation (YCHT) in normal and CCl-intoxicated liver injury rats. Part 1: Metabolic profiles from the liver-centric perspective.

J Ethnopharmacol 2019 Jun 20;237:81-91. Epub 2019 Mar 20.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

Ethnopharmacological Relevance: Yin-Chen-Hao Tang (YCHT), derived from "Treatise on Febrile Diseases" in ancient China, has been a very popular hepatoprotective three-herb formula in China and Japan, although its chemical base remains unclear.

Aim Of This Study: As the first step in revealing the hepatoprotective chemical base of YCHT, we aimed to clarify the absorbed ingredients and associated metabolic pathways for orally dosed YCHT in both normal and liver injury rats from a liver-centric perspective.

Materials And Methods: With the aid of 10 reference compounds, the absorbed ingredients and generated metabolites were systematically characterized by high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF) in the portal vein plasma (the plasma before hepatic disposition) - liver - systemic plasma (the plasma after hepatic disposition), following oral administration of YCHT in normal and CCl-induced liver injury rats.

Results: A total of 38 compounds with six chemical structures, consisting of 10 prototypes and 28 metabolites generated through 9 biotransformations, were absolutely or tentatively identified, and 25 compounds were first reported on YCHT treatments. Among them, 8 compounds were absolutely confirmed by comparing with standard substances, and some had published hepatoprotective activities. Compared with the 35, 15, and 29 compounds identified in the portal vein plasma, liver, and systemic plasma of normal rats, respectively, the corresponding numbers of characterized compounds were 37, 13 and 29 in the liver injury rats.

Conclusions: Sulfation and glucuronidation were the predominant biotransformations, and intestinal metabolism, prior to hepatic metabolism, occurred for most compounds. CCl-induced liver injury caused only slight changes in the metabolic profiles of rats orally administered YCHT. These results provided the precondition for further quantitative analysis and pharmacodynamic screening of compounds in YCHT.
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http://dx.doi.org/10.1016/j.jep.2019.03.044DOI Listing
June 2019

Exploration of the hepatoprotective chemical base of an orally administered herbal formulation (YCHT) in normal and CCl-intoxicated liver injury rats. Part 2: Hepatic disposition in vivo and hepatoprotective activity in vitro.

J Ethnopharmacol 2019 May 22;236:161-172. Epub 2019 Feb 22.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Hai Ke Road Zhangjiang, Pudong, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Ethnopharmacological Relevance: Yin-Chen-Hao Tang (YCHT) has been a very popular, hepatoprotective three-herb formula with an unclear chemical base.

Aim Of This Study: To reveal the hepatoprotective chemical base of oral-dosed YCHT, we bridged the hepatic disposition of six compounds in vivo and their hepatoprotection in vitro.

Materials And Methods: In vivo, following the oral administration of YCHT in normal and CCl-induced liver injury rats, the determinations of chlorogenic acid, 4-hydroxyacetophenone, geniposide, genipin, rhein and emodin were conducted in the portal vein plasma, the liver, and the systemic plasma. In vitro, the hepatoprotective activities of these compounds were determined in the CCl-induced HepG2 cells.

Results: Consistent with the highest content in YCHT, geniposide had the highest exposure in vivo. Inconsistent with the negligible content, rhein, 4-hydroxyacetophenone, emodin and genipin showed substantial hepatic accumulations. In contrast, chlorogenic acid, an ingredient that has a high content in YCHT, elicited no hepatic exposure. In normal rats, the hepatic disposition prevented the compounds entering into the systemic plasma from the portal vein plasma by 44.9-100%, except for rhein. CCl-induced liver injury caused a decreased hepatic exposure of 4-hydroxyacetophenone, rhein and emodin by 50%. In vitro, all six compounds exerted the hepatoprotection by increasing cell viability, decreasing hepatic marker enzymes and inhibiting lipid peroxidation at varying levels.

Conclusion: Geniposide, rhein, emodin, 4-hydroxyacetophenone and genipin directly resisted liver injury in oral-dosed YCHT, while chlorogenic acid likely played an indirect role. This study proved that YCHT exerted hepatoprotection through multiple components and multiple actions. However, close attention should be paid to the possible side effects and oral dosage of YCHT in clinics.
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http://dx.doi.org/10.1016/j.jep.2019.02.022DOI Listing
May 2019

Evaluation of the chemical consistency of Yin-Chen-Hao-Tang prepared by combined and separated decoction methods using high-performance liquid chromatography and quadrupole time-of-flight mass spectrometry coupled with multivariate statistical analysis.

J Sep Sci 2019 May 8;42(9):1664-1675. Epub 2019 Mar 8.

Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Material Medica, Pudong, Shanghai, P. R. China.

In this study, Yin-Chen-Hao-Tang prepared by two decoction methods, namely, combined decoction (modern decoction method) and separated decoction (traditional decoction method), was analyzed by high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. The acquired datasets containing sample codes, t -m/z pairs and ion intensities were processed with multivariate statistical analyses, such as principal component analysis and an orthogonal partial least squared discriminant analysis model, to globally compare the chemical differences between the different decoction samples. Then, the chemical differences between the combined and separated decoctions were screened out by S-plots generated from the orthogonal partial least squared discriminant analysis model and compared with chemical information from an established in-house library. The six components that contributed the most to the chemical differences were identified as chlorogenic acid, caffeic acid, geniposide, genipin, scopoletin, and 3,5-dicaffeoylquinic acid. The concentrations of genipin and caffeic acid from the separated decoction were higher than those from the combined decoction, indicating that the separated decoction may present a stronger hepatoprotective effect. However, the results still require further investigation through pharmacological and clinical studies. Our findings not only establish a strategy to evaluate chemical consistency of Yin-Chen-Hao-Tang but also provide the scientific basis for using traditional separated decoction method.
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http://dx.doi.org/10.1002/jssc.201800961DOI Listing
May 2019

Enhanced Anti-diabetic Effect of Berberine Combined With Timosaponin B2 in Goto-Kakizaki Rats, Associated With Increased Variety and Exposure of Effective Substances Through Intestinal Absorption.

Front Pharmacol 2019 24;10:19. Epub 2019 Jan 24.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

Inspired by the traditionally clinical application of herb pair - to treat diabetes, a combination of plant ingredients, timosaponin B2 (TB-2) and berberine (BBR), was evaluated for their anti-diabetic efficacy and cooperative mechanisms. The efficacy and pharmacokinetics of orally administered TB-2 (33.3 mg/kg/day), BBR (66.7 mg/kg/day), and TB-2+BBR (100 mg/kg/day) were evaluated in spontaneously non-obese diabetic Goto-Kakizaki (GK) rats, and metformin (200 mg/kg/day) was used as a positive control. The comparative exposure of the parent drugs, timosaponin A3 (TB-2 metabolite), and M1-M5 (BBR metabolites) was quantified in the portal vein plasma (before hepatic disposition), liver, and systemic plasma (after hepatic disposition) of normal rats on single and combination treatments. Cooperative mechanism of TB-2 and BBR on intestinal absorption and hepatic metabolism was investigated in Caco-2 cells and primary hepatocytes, respectively. After a 6-week experiment, non-fasting and fasting blood glucose levels and oral glucose tolerance test results showed that TB-2+BBR treatments (100 mg/kg/day) displayed significantly anti-diabetic efficacy in GK rats, comparable to that on metformin treatments. However, no significant improvement was observed on TB-2 or BBR treatments alone. Compared to single treatments, combination treatments led to the increased circulating levels of BBR by 107% in GK rats. In normal rats, the hepatic exposure of BBR, timosaponin A3, and M1-M5 was several hundred folds higher than their circulating levels. Co-administration also improved the levels in the plasma and liver by 41-114% for BBR, 141-230% for TB-2, and 12-282% for M1-M5. , the interaction between TB-2 and BBR was mediated by intestinal absorption, rather than hepatic metabolism. Combining TB-2 and BBR enhanced the anti-diabetic efficacy by increasing the variety of effective substances, including the parent compounds and active metabolites, and improving the levels of those substances through intestinal absorption. This study is a new attempt to assess the effects of combined plant ingredients on diabetes by scientifically utilizing clinical experience of an herb pair.
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http://dx.doi.org/10.3389/fphar.2019.00019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6353801PMC
January 2019

Genomic and GeneChip expression profiling reveals the inhibitory effects of Amorphophalli Rhizoma in TNBC cells.

J Ethnopharmacol 2019 May 4;235:206-218. Epub 2019 Feb 4.

The First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine, Hangzhou, Zhejiang 310006, China. Electronic address:

Ethnopharmacological Relevance: Amorphophalli Rhizoma has been widely used as an adjuvant treatment for advanced or metastatic breast cancer, pancreatic cancer, hepatoma, and malignant lymphoma, but its molecular mechanism of action for treatment of metastatic triple-negative breast cancer (TNBC) is generally poorly understood.

Aim Of The Study: To investigate genomic changes related to the inhibitory effect of Amorphophalli Rhizoma and to elucidate the molecular mechanism of this inhibition in MDA-MB-231 TNBC cells.

Materials And Methods: Gene chip analysis was employed to explore genomic changes caused by Amorphophalli Rhizoma in TNBC cells. Potential classical signaling pathways, upstream regulators, functions, regulatory effects and gene interaction networks were analyzed by Ingenuity Pathway Analysis (IPA). Real-time quantitative PCR (RT-qPCR) and RNA interference (RNAi) assays were used to clarify the roles of potential target genes.

Results: In total, 536 significantly upregulated and 648 significantly downregulated genes were identified between the group treated with Amorphophalli Rhizoma extract and that treated with vehicle. Many of these differentially expressed genes (DEGs) in TNBC cells are involved in DNA replication, recombination and repair, the cell cycle, and cellular assembly and organization. Attenuation of KNL1, OLFML2A, RTKN2 and SGO1 gene expression by Amorphophalli Rhizoma significantly induced cell cycle arrest and suppressed cell proliferation and migration.

Conclusions: The inhibitory effects of Amorphophalli Rhizoma in TNBC cells likely occur through regulation of the spindle checkpoint, chromosomal and centrosomal instability, and cell membrane stability.
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http://dx.doi.org/10.1016/j.jep.2019.02.004DOI Listing
May 2019

Wenshen Zhuanggu formula mitigates breast cancer bone metastasis through the signaling crosstalk among the Jagged1/Notch, TGF-β and IL-6 signaling pathways.

J Ethnopharmacol 2019 Mar 18;232:145-154. Epub 2018 Dec 18.

Department of Breast Surgery (Integrated Traditional and Western Medicine), Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 South Wanping Road, Shanghai 200032, China; Pharmacology Laboratory of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 South Wanping Road, Shanghai 200032, China. Electronic address:

Ethnopharmacological Relevance: Advanced breast cancer frequently metastasizes to the bone, resulting in patient morbidity and mortality. The interaction of tumor cells with osteoclasts and osteoblasts seriously affects the occurrence and development of bone metastasis in breast cancer. The signaling crosstalk among the Jagged1/Notch, TGF-β and IL-6 signaling pathways plays a significant role in the context of bone metastasis.

Aim Of The Study: Although Wenshen Zhuanggu (WSZG) formula efficiently decreased the risk of bone metastases in tumor-bearing mice, it remains unclear how WSZG formula regulates the interaction of cancer cells with osteoclasts and osteoblasts in bone metastasis of breast cancer.

Materials And Methods: In this study, we investigated the role of WSZG formula in the progress of bone metastasis in breast cancer and focused on the cell-cell interactions of tumor cells with osteoclasts and osteoblasts. Western blotting and quantitative real-time PCR were utilized to evaluate the inhibitory activities of WSZG formula on Jagged1 expression both in vivo and in vitro. Osteoblast co-culture and osteoclastogenesis co-culture were applied to analyze the effects of WSZG formula on the interaction of tumor cells with osteoclasts and osteoblasts. A breast cancer xenograft model was also used to test the inhibitory effects of WSZG formula on bone metastasis in breast cancer.

Results: WSZG formula decreased Jagged1 expression in osteolytic lesions in the breast cancer xenograft model. Additionally, WSZG formula decreased Jagged1 expression in tumor cell culture alone or co-culture with pre-osteoclasts and osteoblasts. In addition, WSZG formula decreased Jagged1 expression in Jagged1-overexpressing tumor cells.

Conclusion: The results of this study suggest that WSZG formula mitigates breast cancer bone metastasis through the Jagged1/Notch signaling pathway mediated by TGF-β and IL-6.
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http://dx.doi.org/10.1016/j.jep.2018.12.023DOI Listing
March 2019

Simultaneous determination of eight bioactive compounds by LC-MS/MS and its application to the pharmacokinetics, liver first-pass effect, liver and brain distribution of orally administrated Gouteng-Baitouweng (GB) in rats.

J Chromatogr B Analyt Technol Biomed Life Sci 2018 May 9;1084:122-131. Epub 2018 Mar 9.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Only focusing on the circulating levels is insufficient for the comprehensive understanding of the physiological disposition of herbal medicine in vivo. Therefore, we conducted the comprehensive investigation on the in vivo dynamic process of orally administrated Gouteng-Baitouweng (GB), a classical herb pair with anti-Parkinson potentials. Serving as the technical base, a sensitive and selective liquid chromatography-tandem mass spectrometry method was established and validated in the plasma, liver and brain, for simultaneous determination of five alkaloids (rhynchophylline, isorhynchophylline, corynoxeine, isocorynoxeine and geissoschizine methyl ether) and three saponins (anemoside B4, anemoside A3 and 23-hydroxybetulinic acid). Following liquid-liquid extraction, favorable chromatographic behaviors of eight analytes were obtained on Waters Xbrigde C18 column within 13 min. This method elicited good linearity for the analytes at the concentration range of 0.3-1000 or 1.8-6000 ng/mL with favorable precision, accuracy and stability. Following oral administration of GB (25 g/kg) in rats, this method was applied to the quantitative analysis in the portal vein plasma, liver, systemic plasma, and brain. Consequently, anemoside B4 was of the highest exposure, followed by 23-hydroxybetulinic acid, anemoside A3, rhynchophylline and isocorynoxeine in vivo. Notably, three saponins were all observed with certain exposure in the brain, along with rhynchophylline at low levels. Besides, five alkaloids and 23-hydroxybetulinic acid underwent serious liver first-pass effect. Hence, the pharmacokinetics, liver first-pass effect, liver and brain distribution of ingredients in GB were clarified, which laid a solid foundation for interpreting its efficacy and safety.
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http://dx.doi.org/10.1016/j.jchromb.2018.03.013DOI Listing
May 2018

A sensitive HPLC-MS/MS method for the simultaneous determination of anemoside B4, anemoside A3 and 23-hydroxybetulinic acid: Application to the pharmacokinetics and liver distribution of Pulsatilla chinensis saponins.

Biomed Chromatogr 2018 Mar 22;32(3). Epub 2017 Nov 22.

Shanghai Institute of Material Medica, Chinese Academy of Science, Shanghai, China.

Pulsatilla chinensis saponins, the major active components in the herb, have drawn great attention as potential hepatitis B virus infection and hepatoma treatments. Here, a sensitive and accurate HPLC-MS/MS method was established for simultaneous determination of three saponins - anemoside B4, anemoside A3 and 23-hydroxybetulinic acid - in rat plasma and liver, and fully validated. The method was successfully applied to a pharmacokinetics and liver distribution study of P. chinensis saponins. Consequently, 23-hydroxybetulinic acid, with an extremely low content in the P. chinensis saponins, exhibited the highest exposure in the liver and in sites before and after hepatic disposition, namely, in the portal vein plasma and systemic plasma, followed by anemoside B4, which showed the highest content in the herb, whereas anemoside A3 displayed quite limited exposure. The hepatic first-pass effects were 71% for 23-hydroxybetulinic acid, 27% for anemoside B4 and 37% for anemoside A3, corresponding to their different extents of liver distribution. To our knowledge, this is the first investigation on the liver first-pass effect and distribution of P. chinensis saponins to date. These results also provide valuable information for the understanding of the pharmacological effect of P. chinensis saponins on liver diseases.
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http://dx.doi.org/10.1002/bmc.4124DOI Listing
March 2018

Material basis studies of anti-Influenza A active ingredients in Tanreqing Injection.

Biomed Chromatogr 2018 Feb 10;32(2). Epub 2017 Oct 10.

Shanghai Institutes of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

Tanreqing Injection (TRQ) has been used primarily in treating infections of the upper respiratory tract and serious influenza in China, as a classical compound herbal recipe. TRQ had been demonstrated to have effects of clearing heat, eliminating phlegm, detoxification, reducing inflammation and alleviating cough. The survival rate, histopathology of lungs and viral titers in mice were evaluated in this study to verify the curative effect of TRQ. However, there is not enough information about the components. In the present study, a high-performance and practical LC/QTOF/MS method was developed for characterization and identification of the natural ingredients in TRQ. A total of 60 compounds, including 10 amino acids, 10 iridoid glucosides, 14 flavonoids, 13 other phenolic compounds, 10 steroid acids and three other compounds, were characterized and identified. We also confirmed the material basis of anti-Influenza A active ingredients in TRQ. Therefore, we have developed an accurate analytical method. LC/QTOF/MS could be applied for identification the complex components in traditional Chinese medicine.
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http://dx.doi.org/10.1002/bmc.4097DOI Listing
February 2018

Systematic and comprehensive strategy for metabolite profiling in bioanalysis using software-assisted HPLC-Q-TOF: magnoflorine as an example.

Anal Bioanal Chem 2016 Mar 12;408(9):2239-54. Epub 2016 Feb 12.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Metabolite profiling plays a crucial role in drug discovery and development, and HPLC-Q-TOF has evolved into a powerful and effective high-resolution analytical tool for metabolite detection. However, traditional empirical identification is laborious and incomplete. This paper presents a systematic and comprehensive strategy for elucidating metabolite structures using software-assisted HPLC-Q-TOF that takes full advantage of data acquisition, data processing, and data mining technologies, especially for high-throughput metabolite screening. This strategy has been successfully applied in the study of magnoflorine metabolism based on our previous report of its poor bioavailability and drug-drug interactions. In this report, 23 metabolites of magnoflorine were tentatively identified with detailed fragmentation pathways in rat biological samples (urine, feces, plasma, and various organs) after i.p. or i.g. administration, and for most of these metabolites, the metabolic sites were determined. The phase I biotransformations of magnoflorine (M1-M7, M10-M14) consist of demethylation, dehydrogenation, hydroxylation, methylene to ketone transformation, N-ring opening, and dehydroxylation. The phase II biotransformations (M8, M9, and M15-M23) consist of methylation, acetylation, glucuronidation, and N-acetylcysteine conjugation. The results indicate that the extensive metabolism and wide tissue distribution of magnoflorine and its metabolites may partly contribute to its poor bioavailability and drug-drug interaction, and i.p. administration should thus be a suitable approach for isolating magnoflorine metabolites. In summary, this strategy could provide an efficient, rapid, and reliable method for the structural characterization of drug metabolites and may be applicable for general Q-TOF users.
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http://dx.doi.org/10.1007/s00216-015-9254-5DOI Listing
March 2016

Structural elucidation and protective role of a polysaccharide from Sargassum fusiforme on ameliorating learning and memory deficiencies in mice.

Carbohydr Polym 2016 Mar 12;139:150-8. Epub 2015 Dec 12.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Rd., Zhangjiang, Pudong, Shanghai 201203, People's Republic of China. Electronic address:

A fucoidan, Sargassum fusiforme polysaccharide 65 (SFPS65) A, was isolated from a brown alga (S. fusiforme). SFPS65A had an estimated molecular weight of 90kDa and showed αD(20) -74.3288 (c 0.05, H2O). SFPS65A is composed of fucose, galactose, xylose, glucose, glucuronic acid, and mannose in the ratio of 19.23:9.58:6.64:1:6.52:2.57. The structural features of SFPS65A were investigated using composition analysis, methylation analysis, infrared spectrum, nuclear magnetic resonance spectroscopy, and electrospray ionization quadruple time-of-flight tandem mass spectroscopy. Results showed that SFPS65A has a main chain composed of →3)-β-l-Fucp-(1→3,4)-β-l-Fucp-(1→3,4)-β-l-Fucp-(1→ and connected with →3,4)-α-d-GlcAp-(1→, →4)-β-d-Xylp-(1→, →4)-α-d-Galp-(1→, →3,6)-α-d-Manp-(1→ alternately. The branches at O-3 of the fucosyl residue and O-3 of the hexosyl residues may include sulfate, →4)-β-l-Fucp-(1→, β-d-Xylp-(1→, and β-d-Xylp-(1→. SFPS65A exhibited an activity on Alzheimer's disease in vivo in the pharmacological experiments by increasing the cognitive abilities of scopolamine-, ethanol-, and sodium nitrite-treated mice against memory deficits.
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http://dx.doi.org/10.1016/j.carbpol.2015.12.019DOI Listing
March 2016

Fragmentation patterns study of iridoid glycosides in Fructus Gardeniae by HPLC-Q/TOF-MS/MS.

Biomed Chromatogr 2014 Dec 30;28(12):1795-807. Epub 2014 Apr 30.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Rd., Shanghai, 201203, People's Republic of China; Department of Clinical Pharmacology, Shuguang hospital affiliated to Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rd, Shanghai, 201203, People's Republic of China.

Iridoid glycosides (IGs), the major constituents in Fructus Gardeniae, have demonstrated various pharmacological activities, but there is no systematic chemical profile of IGs in Fructus Gardeniae in the published literature until now. Therefore, it is imperative that a rapid and sensitive high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (HPLC-Q/TOF-MS/MS) method is established for comprehensive characterization of IGs in Fructus Gardeniae. Firstly, the fragmentation patterns of six known IGs were investigated and proposed and further concluded the diagnostic fragment ions and characteristic fragmentation pathways. Then, based on the summarized fragmentation patterns and the known compounds in the literatures, the other IGs in Fructus Gardeniae were identified successively. As a result, a total of 20 IGs were identified, of which three pairs of epimers were structurally characterized and differentiated. More importantly, one compound, the isoshanzhiside methyl ester, was tentatively identified as a new compound. The results of this study demonstrate the superiority of HPLC-MS with a high-resolution mass spectrometer for the rapid and sensitive structural elucidation of the multiple groups of constituents in Fructus Gardeniae.
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http://dx.doi.org/10.1002/bmc.3223DOI Listing
December 2014

Identification of multiple constituents from seed of Vaccaria segetalis with an adsorbent-separation strategy based on liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

Rapid Commun Mass Spectrom 2014 Jun;28(11):1243-57

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 HaiKe Rd, Pudong, 201203, Shanghai, China.

Rationale: Seeds of Vaccaria segetalis (Wang-Bu-Liu-Xing in Chinese) are mainly used in traditional Chinese medicine for the treatment of amenorrhea, breast infections, and edema. The study was designed to identify the components and metabolites of Wang-Bu-Liu-Xing.

Methods: A novel methodology combining an adsorbent-separation strategy with analysis by liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (LC/QTOF-MS/MS) was established to identify the components of Wang-Bu-Liu-Xing. The adsorbent-separation technique was applied on macroporous resin (adsorbents). Different concentrations of ethanol (30%, 60%, and 95%), which covered high-to-low polarity ranges, were chosen as the elution solvent, respectively. The QTOF mass spectrometer was operated in negative ion mode with an electrospray ionization source.

Results: A total of 52 components were successfully identified in the Wang-Bu-Liu-Xing decoction based on the fragmentation pathways and QTOF high-accuracy mass spectral analysis. To the best of our knowledge, several new saponins were reported for the first time. A total of 20 compounds, which included 10 prototypes and 10 metabolites, were also identified in rat plasma and urine after oral administration of Wang-Bu-Liu-Xing decoction.

Conclusions: An integrated adsorbent-separation strategy is powerful and reliable for global detection and identification of complex components in herbal prescriptions. The components identified in rat biofluids may also provide helpful chemical information for further pharmacology and active mechanism study on this herb.
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http://dx.doi.org/10.1002/rcm.6893DOI Listing
June 2014

Anti-depressive activities and biotransformation of timosaponin B-III and its derivatives.

Nat Prod Res 2014 22;28(18):1446-53. Epub 2014 Apr 22.

a Harbin University of Commerce , Harbin 150076 , P.R. China.

Timosaponin B-III (TB-III) is a steroidal saponin isolated from the rhizome of Anemarrhenae asphodeloides (Liliaceae). The biotransformation of TB-III by β-glucosidase was investigated. Three biotransformation products were isolated and their structures were identified as timosaponin B-III-a (M1), (20R,25S)-5β-spirostane-3β-ol-3-O-β-D-glucopyranosyl-(1 → 2)-β-D-galacopyanoside (M2) and timosaponin AIII (M3). Then the four compounds were evaluated for their anti-depressive activity in mice by the open field test, tail suspension test and forced swimming test. As a result, TB-III, M1 and M3 exhibited modest anti-depressive activity. Structure-activity relationships were investigated and the preliminary conclusions are summarised as follows: the glycosyl at C-3 and C-26 can increase the activity, the double bond between C-20 and C-22 might be important for the anti-depressive activity, the R-configuration at C-22 and S-configuration at C-20 are necessary for its anti-depressive activity.
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http://dx.doi.org/10.1080/14786419.2014.910663DOI Listing
December 2014

Structural investigation and immunological activity of a heteropolysaccharide from Sargassum fusiforme.

Carbohydr Res 2014 May 11;390:28-32. Epub 2014 Mar 11.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Rd., Zhangjiang, Pudong, Shanghai 201203, PR China. Electronic address:

A heteropolysaccharide was isolated from the brown alga, Sargassum fusiforme. The heteropolysaccharide was estimated to have a molecular weight of 11kDa and showed [α]D(20) -62.2420 (c 0.05, H2O). SFPS65-B comprised galactose, glucose, mannose, fucose, and galacturonic acid at a ratio of 3.04:1:1.15:2.82:6.51. Its structural features were investigated using composition analysis, methylation analysis, IR, NMR spectroscopy, and ESI-Q-TOF MS spectroscopy. Results showed that SFPS65-B contained the backbone of →4)-α-GalAp-(1→4)-α-Hexp-(1→4)-α-GalAp-(1→4)-α-Fucp-(1→4)-α-GalAp-(1→. The sulfated unit and terminal fucose residues were attached onto the backbone through the O-2 of some galactose residues. Results also showed that SFPS65-B had a good effect on thymus and spleen indices at a dose of 100mg/kg upon immunosuppression in cyclophosphamide-treated mice.
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http://dx.doi.org/10.1016/j.carres.2014.02.027DOI Listing
May 2014

Study on the PK profiles of magnoflorine and its potential interaction in Cortex phellodendri decoction by LC-MS/MS.

Anal Bioanal Chem 2014 Jan 15;406(3):841-9. Epub 2013 Dec 15.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Rd, Pudong, Shanghai, 201203, China.

Magnoflorine, an aporphine alkaloid in Cortex phellodendri, is increasingly attracting research attention because of its antidiabetic effects. However, at present, little information on its pharmacokinetics (PK) in vivo is available. In this study, a sensitive, rapid, and selective method was developed to determine the magnoflorine content in rat plasma using liquid chromatography-tandem mass spectrometry. Following liquid-liquid extraction, the calibration curve showed good linearity within the concentration range of 2.93 to 1,500 ng ml(-1). The intra- and inter-day precisions were all below 7.8 %, and the accuracy ranged from 94.9 to 103.4 %. The method was successfully applied in investigating the PK of magnoflorine in rats. The compound had low bioavailability, a high absorption rate, and a high elimination rate. However, area under the curve, T 1/2, and MRT increased approximately twofold when the same dosage of the compound was administered in a C. phellodendri decoction (20.8 g kg(-1)). Moreover, T max was prolonged from 0.3 to 3.33 h. Furthermore, a comparison of coadministration of the mixture group, magnoflorine (40 mg kg(-1)) and berberine (696.4 mg kg(-1)), with the C. phellodendri decoction group, revealed that no statistical difference (P > 0.05) was found in the parameter AUC, and certain similar changes in the PK trend to the herbal medicine group were also observed. These results suggested that oral administration of the herbal medicine decreased the absorption and elimination rates of magnoflorine and increased its bioavailability. Berberine played a significant role in interacting with magnoflorine and in affecting the PK profiles of magnoflorine in the C. phellodendri decoction group.
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http://dx.doi.org/10.1007/s00216-013-7530-9DOI Listing
January 2014

HPLC-Q-TOF-MS/MS for analysis of major chemical constituents of Yinchen-Zhizi herb pair extract.

Biomed Chromatogr 2014 Apr 9;28(4):475-85. Epub 2013 Oct 9.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Rd, Zhangjiang, Pudong, Shanghai, 201203, People's Republic of China; Department of Clinical Pharmacology, Shuguang hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.

The Yinchen-Zhizi herb pair (YZHP) consists of Herba Artemisiae Scopariae (Yinchen in Chinese) and Fructus Gardeniae (Zhizi in Chinese), and is mainly used to treat icteric hepatitis, itching skin and eczema. However, the bioactive constituents responsible for the pharmacological effects of YZHP are still unclear to date. In this work, a rapid and sensitive method was established to comprehensively study the constituents in YZHP extract by HPLC-Q-TOF MS/MS. The analysis was performed on an HPLC system equipped with an Agilent poroshell 120 EC-C18 column (100 × 2.1 mm, 2.7 mm) working in a gradient elution program coupled to quadrupole-time-of-flight mass spectrometry operating in the negative ion mode. As a result, a total of 46 compounds including 17 from Herba Artemisiae Scopariae and 36 from Fructus Gardeniae were detected and tentatively identified in YZHP extract by comparing the retention time and mass spectrometry and retrieving the reference literature. More importantly, a series of constituents, such as many iridoid glycosides, were reported for the first time in this formula. The HPLC-Q-TOF MS/MS method was developed and utilized successfully to identify the major constituents in YZHP extract and would be helpful for further metabolism and pharmacology research on YZHP.
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http://dx.doi.org/10.1002/bmc.3057DOI Listing
April 2014

Metabolism and tissue distribution study of Vaccaria seeds (Wang-Bu-Liu-Xing) in benign prostatic hyperplasia model rat: toward an in-depth study for its bioactive components.

J Pharm Biomed Anal 2013 Nov 7;85:218-30. Epub 2013 Aug 7.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 HaiKe Road, Pudong, 201203 Shanghai, China.

Vaccaria seeds (Wang-Bu-Liu-Xing), a well-known traditional Chinese medicine (TCM), has been used as an emperor herb of many ancient formulas to treat benign prostatic hyperplasia (BPH) in clinic. However, its metabolism and tissue distribution, especially in the target tissue, had not been investigated so far. Based on the hypothesis that the components which exert effect against BPH of Vaccaria seeds would be measureable in target tissue (prostate), in vivo metabolism and tissue distribution of Vaccaria seeds in rats were profiled using a specific and sensitive high performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (LC-QTOF-MS/MS). As a result, 19 major constituents in the Vaccaria seeds decoction and 19 constituents in rat plasma, feces and tissues after oral administration of Vaccaria seeds decoction were identified. Accurate mass measurement for molecular ions and characteristic fragment ions could represent reliable identification criteria for these compounds. Two prototypes were detected in prostate. An in vitro metabolism analysis of them was studied after incubation with rat intestinal flora and rat liver microsome (RLM) in this paper, which is helpful for further investigation of the potential effect of these two components. The result of this study provided meaningful information for further pharmacology research on Vaccaria seeds.
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http://dx.doi.org/10.1016/j.jpba.2013.07.037DOI Listing
November 2013

Analysis and detection of the chemical constituents of Radix Polygalae and their metabolites in rats after oral administration by ultra high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry.

J Pharm Biomed Anal 2013 Nov 26;85:1-13. Epub 2013 Jun 26.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China.

Radix Polygalae (RP), the dried root of Polygala tenuifolia Willd., is a well-known traditional Chinese medicine to mediate sedative, antipsychotic, cognitive improving, neuroprotective, and anti-inflammatory therapeutic effects on the central nervous system. In this work, ultra high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC/ESI-Q-TOF-MS/MS) was established for the separation and characterization of the chemical constituents in Radix Polygalae and their metabolites in rat plasma and urine after oral administration. Samples were separated on an Agilent Zorbax Eclipse Plus-C18 column (100mm×2.1mm, 1.8μm) with 0.1% formic acid aqueous solution and acetonitrile as the mobile phase under gradient conditions. Overall, 50 compounds were characterized from the RP, 9 of which are to our knowledge reported for the first time. In vivo, 10 components and 2 metabolites were observed in rat plasma, and 27 components and 7 metabolites were detected in rat urine. The results from this work improve our understanding on the chemical constituents of RP and their metabolic profiling.
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http://dx.doi.org/10.1016/j.jpba.2013.06.011DOI Listing
November 2013

Analysis of multiple constituents in Cong-Ming-Tang, a Chinese herbal formula for the treatment of amnesia, by high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

Phytochem Anal 2013 Nov-Dec;24(6):677-88. Epub 2013 Jul 9.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, People's Republic of China.

Introduction: Cong-Ming-Tang (CMT), named smart-soup in English, is a well-known traditional Chinese medicine formula for the treatment of amnesia in China. However, the isolation, purification and identification procedures of the major bioactive constituents in CMT are difficult and time consuming.

Objective: To establish a rapid and sensitive high-performance liquid chromatography/electrospray ionisation with quadrupole time-of-flight tandem mass spectrometry (HPLC-QTOF/MS/MS) method that could be applied to rapidly separate and identify the major bioactive constituents in CMT.

Methods: Methanolic extract of CMT was used for HPLC-QTOF/MS/MS analysis. Separation was performed on an Agilent Poroshell 120 EC- C18 column (2.7 ×100 mm .i.d., 2.7 µm) with 0.1% formic acid aqueous solution and acetonitrile as the mobile phase under gradient conditions. Both positive and negative ion modes were employed.

Results: This analytical tool allowed the identification of 55 compounds from CMT formulae by comparing their retention times and MS spectra with those of authentic compounds or literature data in both positive and negative ion modes, including 4 xanthone C-glycosides, 4 sucrose esters, 11 oligosaccharide multi-esters,15 triterpene saponins, 15 triterpene acids, 2 lignans and 4 phenylpropanoids. Onjisaponin MF was tentatively elucidated as a new triterpene saponin based on the summarised fragmentation rules.

Conclusion: HPLC-QTOF/MS/MS provides a new powerful approach to identify the major chemical constituents in CMT rapidly and accurately. This study proposed a series of potential bioactive components without preparative isolation from the crude extract of CMT and indicated that the HPLC-QTOF/MS/MS method also can be a promising tool for the analysis of other traditional Chinese medicines.
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http://dx.doi.org/10.1002/pca.2454DOI Listing
May 2014

Oridonin ameliorates lupus-like symptoms of MRL(lpr/lpr) mice by inhibition of B-cell activating factor (BAFF).

Eur J Pharmacol 2013 Sep 24;715(1-3):230-7. Epub 2013 May 24.

Department of Laboratory Medicine, Changzhen Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.

Oridonin, a pharmacologically safe agent extracted from Isodon Serra, has been shown to possess potent anti-inflammatory properties. However, it is not clear whether Oridonin affects B-cell activating factor (BAFF) expression, thereby exerting beneficial effects in the treatment of BAFF-associated autoimmune diseases such as systemic lupus erythematosus (SLE). Thus, the current study aimed to find the function of Oridonin in regulation of BAFF and amelioration of SLE. In vitro, we explored the effect of Oridonin on BAFF expression and production in mouse macrophages. Moreover, using a spontaneous murine SLE model, we investigated the role of Oridonin delivery in the treatment of lupus-like disease in MRL(lpr/lpr) mice, by measuring the changes in lupus symptoms, renal damage, BAFF expression, and B cell subsets. Our results showed that Oridonin significantly inhibited BAFF expression in mouse macrophages by suppressing the transcriptional activation of its promoter. And in vivo administration of Oridonin efficiently ameliorated the serological and clinical manifestations of SLE in MRL(lpr/lpr) mice, as shown by increased survival benefit, reduced proteinuria levels, diminished production of specific auto-antibodies, and attenuated renal damage, in association with down-regulation of BAFF and a lower rate of B-cell maturation and differentiation. Thus, it suggests that Oridonin will serve as a novel natural therapeutic strategy for SLE by inhibition of BAFF.
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http://dx.doi.org/10.1016/j.ejphar.2013.05.016DOI Listing
September 2013

Characterization of multiple absorbed constituents in rats after oral administration of Paederia scandens decoction.

Biomed Chromatogr 2012 Jul;26(7):863-8

Harbin University of Commerce, Harbin 150076, People's Republic of China.

Paederia scandens (Lour.) Merri. (Jishiteng in Chinese) is a Chinese traditional medicine widely used in treating various diseases. However, its active components have remained unknown. In the present study, a rapid and sensitive method by high-performance liquid chromatography coupled with electrospray ionization mass spectrometry (HPLC-MSn) techniques was employed to investigate the absorbed constituents in rats after oral administration of Paederia scandens decoction. By comparing their MS data with those of authentic compounds and published data, a total of six compounds (paederosid, 1; paederosidic acid, 2; paederosidic acid methyl ester, 3; 6-hydroxy geniposide, 4; asperuloside, 5; and deacetyl asperuloside, 6) were identified in the P. scandens decoction samples. In addition, a total of seven compounds, including three iridoid glucosides and four of their metabolites, were identified in rat urine samples after administration. In addition, six compounds, including four iridoid glucosides and two of their metabolites, were identified in rat serum samples after administration. Our results significantly narrow the range of potentially active compounds in P. scandens decoction, and build a solid foundation for future research on its mechanism.
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http://dx.doi.org/10.1002/bmc.1743DOI Listing
July 2012

Metabolism and pharmacokinetics of mangiferin in conventional rats, pseudo-germ-free rats, and streptozotocin-induced diabetic rats.

Drug Metab Dispos 2012 Nov 2;40(11):2109-18. Epub 2012 Aug 2.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

To clarify the role of the intestinal flora in the absorption and metabolism of mangiferin and to elucidate its metabolic fate and pharmacokinetic profile in diabetic rats, a systematic and comparative investigation of the metabolism and pharmacokinetics of mangiferin in conventional rats, pseudo-germ-free rats, and streptozotocin (STZ)-induced diabetic rats was conducted. Forty-eight metabolites of mangiferin were detected and identified in the urine, plasma, and feces after oral administration (400 mg/kg). Mangiferin underwent extensive metabolism in conventional rats and diabetic rats, but the diabetic rats exhibited a greater number of metabolites compared with that of conventional rats. When the intestinal flora were inhibited, deglycosylation of mangiferin and sequential biotransformations would not occur. Pharmacokinetic studies indicated a 2.79- and 2.35-fold increase in the plasma maximum concentration and the area under the concentration-time curve from 0 to 24 h of mangiferin in diabetic rats compared with those for conventional rats, whereas no significant differences were observed between conventional rats and pseudo-germ-free rats. Further real-time quantitative reverse transcription-polymerase chain reaction results indicated that the multidrug resistance (mdr) 1a level in the ileum increased, whereas its level in the duodenum and the mdr1b mRNA levels in the duodenum, jejunum, and ileum decreased in diabetic rats compared with those in conventional rats. With regard to the pseudo-germ-free rats, up-regulated mdr1a mRNA levels and down-regulated mdr1b mRNA levels in the small intestines were observed. The diabetic status induced increased UDP-glucuronosyltransferase (UGT) 1A3, UGT1A8, UGT2B8, and sulfotransferase (SULT) 1A1 mRNA levels and decreased catechol-O-methyltransferase (COMT), UGT2B6, UGT2B12, and SULT1C1 mRNA levels. These results might partially explain the different pharmacokinetic and metabolic disposition of mangiferin among conventional and model rats.
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http://dx.doi.org/10.1124/dmd.112.045849DOI Listing
November 2012