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Sun Q.,Shanghai University of Traditional Chinese Medicine | Sun Q.,Shanghai R and nter for Standardization of Chinese Medicines | Chou G.,Shanghai University of Traditional Chinese Medicine | Chou G.,Shanghai R and nter for Standardization of Chinese Medicines
PLoS ONE | Year: 2015

Two 2″-isopropenyl dihydrofuran isoflavonoids (1 and 3), one 2″-isopropenyl dihydrofuran chromone (2), as well as 13 known compounds were isolated from the herbs of Crotalaria albida. Their structures and relative configurations were elucidated via NMR and HRESIMS analyses. The 2″ S absolute configuration of 1 and 2 were deduced by comparing their NOESY spectra with that of 3, which was determined via single crystal X-ray diffraction (CuKα). The 3R absolute configuration of 1 was determined by CD. Compounds 1, 2, and 3 inhibit the adipocyte differentiation and lipid accumulation of 3T3-L1 through down-regulation of PPAR-γ activity. © 2015 Sun, Chou. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Source


Ye Y.,Shanghai University of Traditional Chinese Medicine | Ye Y.,Hong Kong Baptist University | Chou G.-X.,Shanghai University of Traditional Chinese Medicine | Chou G.-X.,Shanghai R and nter for Standardization of Chinese Medicines | And 4 more authors.
Integrative Cancer Therapies | Year: 2011

The aims of this study were to isolate sesquiterpene compounds from the largehead atractylodes rhizome (LAR) and to investigate their effects on B16 cancer cells. A total of 8 sesquiterpenes from LAR were identified, of which eudesm-4 (15), 7-diene-9α, 11-diol (7) was isolated for the first time. All 8 compounds inhibited growth of B16 cells, and atractylenolide I (AT-I), atractylenolide II (AT-II), and atractylenolactam (ATR) were the most potent, with IC50 values of 76.46, 84.02, and 54.88 μM, respectively. Monomer lactone or lactam structures in the 8 compounds appeared to be critical for their antiproliferative activities. In addition, AT-I, AT-II, and ATR could induce cell differentiation and inhibit cell migration. Western blot analysis indicated that 2 of the compounds, AT-I and AT-II, could inactivate ERK, where all 3 inhibited AKT activation, suggesting that Ras/ERK and PI3K/AKT signaling pathways are involved in the action mechanisms of the LAR sesquiterpene compounds. © The Author(s) 2011. Source


Ji L.,Shanghai University of Traditional Chinese Medicine | Ji L.,Shanghai R and nter for Standardization of Chinese Medicines | Shen K.,Shanghai University of Traditional Chinese Medicine | Jiang P.,Shanghai University of Traditional Chinese Medicine | And 3 more authors.
Molecular Carcinogenesis | Year: 2011

Andrographolide (ANDRO), isolated from the traditional herbal medicine Andrographis paniculata, is reported to have the potential therapeutic effects for hepatocellular carcinoma (HCC) in our previous reports. Here, we investigated the mechanism of ANDRO-mediated apoptotic cell death, focusing on the involvement of cellular reduced glutathione (GSH) homeostasis and c-Jun NH2-Terminal kinase (JNK). Buthionine sulfoximine (BSO), an inhibitor of cellular GSH biosynthesis, significantly augmented ANDRO-induced cytotoxicity in hepatoma Hep3B and HepG2 cells. BSO depleted cellular GSH, and augmented ANDRO-induced apoptosis, inhibition of colony formation and JNK activation in Hep3B cells. All these effects could be reversed by GSH monoethyl ester (GSH.EE), whose deacetylation replenishes cellular GSH. BSO also augmented ANDRO-induced activation of apoptosis signal-regulating kinase 1 (ASK1), mitogen-activated protein kinase kinase-4 (MKK4) and c-Jun, which are all up-stream or down-stream signals of JNK. Further results showed that JNK inhibitor SP600125 and 420116 both reversed ANDRO-induced cytotoxicity, and SP600125 also decreased ANDRO-increased intracellular GSH and GCL activity. Finally, we showed that in nude mice bearing xenografted Hep3B tumors, BSO improved the inhibition of tumor growth by ANDRO. Taken together, our results suggest that there is a crosstalk between JNK activation and cellular GSH homeostasis, and ANDRO targets this to induce cytotoxicity in hepatoma cells. © 2011 Wiley-Liss, Inc. Source


Wang J.,Shanghai University of Traditional Chinese Medicine | Ji L.,Shanghai University of Traditional Chinese Medicine | Ji L.,Shanghai R and nter for Standardization of Chinese Medicines | Liu H.,Shanghai University of Traditional Chinese Medicine | And 2 more authors.
BioScience Trends | Year: 2010

Dioscorea bulbifera L. is a medicinal plant. The present study was undertaken to investigate the hepatotoxicity induced by D. bulbifera in mice. Through the acute toxicity of various extracts including the EtOAc fraction (EF) and the non-EtOAc fraction (Non-EF) from ethanol, and the ethanol itself, we found that the EF contains the toxic ingredients of D. bulbifera rhizome. On this basis, to study the hepatotoxicity induced by the toxic ingredients, mice were treated with 0.5% sodium carboxymethyl cellulose (CMC-Na) alone or the EF of D. bulbifera rhizome at doses of 80, 160, 320, and 480 mg/kg once daily i.g. for fourteen consecutive administrations. Serum samples were collected for determination of the biomarkers for liver injury, such as, alanine transaminase (ALT) and aspartate transanimase (AST). Hepatic tissues were used to assay for the level of lipid peroxide (LPO), amounts of antioxidants such as glutathione, and activities of antioxidant-related enzymes for liver oxidative-antioxidative status in mice. The results showed that ALT and AST were significantly elevated after fourteen consecutive administrations of the EF of D. bulbifera rhizome. In addition, the level of LPO increased remarkably, while the glutathione amounts, and the activities of the antioxidant-related and glutathione-related enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR) and glutamate-cysteine ligase (GCL) of hepatic tissues all decreased conspicuously, in livers of mice treated with the EF of D. bulbifera rhizome. Taken together, our results indicate that the EF contains the main toxic ingredients of D. bulbifera rhizome, and the mechanism of hepatotoxicity induced by it may be due to liver oxidative stress injury in mice. Source


Qi M.,Shanghai University of Traditional Chinese Medicine | Xiong A.,Shanghai University of Traditional Chinese Medicine | Li P.,Shanghai University of Traditional Chinese Medicine | Yang Q.,Shanghai University of Traditional Chinese Medicine | And 4 more authors.
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2013

In this study, metabolites in the urine samples of rats orally administered with acteoside, a phenylethanoid glycoside compound, were detected and identified using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC/ESI-QTOF-MS) combined with an automated MSE technique. Up to 35 metabolites (19 metabolites of the parent drug and 16 metabolites of the degradation products) were observed, including processes of oxidization, glucuronidation, sulfation, and methyl conjugation. According to the metabolic pathways, acteoside mainly functioned as a prodrug and underwent hydrolysis before being absorbed into the blood. The degradation products, especially caffeic acid and hydroxytyrosol, were involved in further metabolism which was responsible for the low oral bioavailability but obvious pharmacological activities of acteoside. In summary, this work provided valuable information on acteoside metabolism through the rapid and reliable UPLC/ESI-QTOF-MS technique, which could be widely used for the investigation of natural product metabolites. © 2013 Elsevier B.V. Source

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