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Liu Z.,Wuhan Institute of Technology | Liu Z.,Humanwell Healthcare Group Co. | Zhang X.,Wuhan Institute of Technology | Xue P.,Huazhong University of Science and Technology | Zhang H.,Wuhan Institute of Technology
Biomedicine and Pharmacotherapy | Year: 2014

In the article, we investigated the anti-metastasis mechanism of RY10-4, an anti-tumor compound derived from protoapigenone, in breast tumor cells MB-MDA-231. The analog of protoapigenone with an unaromatic B-ring was verified to suppress the proliferation of several tumor cells by previous research that also showed that several tumor progression such as inducing apoptosis and anti-angiogenesis could be acted on by RY10-4. In the article, we investigated the mechanism about how RY10-4 suppressed the invasion of MDA-MB-231. Firstly, the transwells assays with and without matrigel were adapted to evaluate the anti-metastasis and anti-invasion activity. Much research had demonstrated that the ECM and E-cadherin/β-catenin complex play an important role in cell adhesion and the formation of the cell skeleton, and as we knew the abnormal and absent expression of ECM and E-cadherin/β-catenin complex are found in many malignant cells. The result demonstrated that the amount and distribution of E-cadherin/β-catenin complex were backed on track by RY10-4, and the expression of MMP-2/9 in MDA-MB-231, which functions as a major negative factor of ECM, was down-regulated after co-cultured with RY10-4. Furthermore the pathway related to MMP-2/9 and E-cadherin was assessed by the western blot. As the results showed, the MAPK pathway and the spread of β-catenin were affected by RY10-4 to exert the anti-metastasis on MDA-MB-231. Collectively, the research revealed a novel anti-tumor ability of RY10-4 by inhibiting migration and invasion in MDA-MB-231. © 2014 Elsevier Masson SAS. Source

Qian L.-N.,Waterstone Pharmaceuticals Wuhan Co. | Zhang C.-C.,Wuhan National Bioindustry Innovation Park Management Co. | Huang L.,Humanwell Healthcare Group Co.
Chinese Journal of New Drugs | Year: 2016

As new targeted anti-tumor drugs, histone deacetylase(HDAC) inhibitors have become a hot topic in today's oncology research, and these drugs provide more choices for highly effective clinical treatment of tumors. Starting with the representative HDAC inhibitors, this article analyzed the related patent application situation, introduced its technical effect, and analyzed the patent layout of the target drugs in China. Lastly, some advice was put forwarded on new drug research and development and patent layout for domestic research and development institutions and enterprises. © 2016, Chinese Journal of New Drugs Co. Ltd. All right reserved. Source

Huang C.,Huazhong University of Science and Technology | Xu Q.,Soochow University of China | Chen C.,Huazhong University of Science and Technology | Song C.,Huazhong University of Science and Technology | And 6 more authors.
Journal of Chromatography A | Year: 2014

Physalins, uniquely discovered from genus physalis, showed significant bioactivities in many aspects. It is therefore very important for the exploration of natural resources rich of physalins. However, there is no efficient approach for rapid discovery and identification of this class of compounds due to their structural complexity. To address the issue, the fragmentation pathways and correspondingly fragmentation rules of physalins in negative MS/MS mode were thoroughly investigated in this study using seven physalin standards. As a result, diagnostic ions for the rapid screening of physalins and classification of different types of physalins were determined based on their MS/MS fragmentation patterns. On top of that, an integrated approach using UHPLC-QTOF-MS/MS together with a novel three-step data mining strategy was developed for the systematic analysis of physalins in complex samples. Consequently, 46 physalins including 20 novel ones were efficiently discovered and identified from the crude extracts of Ph. alkekengi calyx. The present study laid a foundation for future study of different parts of Ph. alkekengi and other physalis species with regard to rapid discovery of novel physalins. In addition, this study provided a base for establishing a quality control method of the raw materials of Ph. alkekengi according to the profile of physalins. © 2014 Elsevier B.V.. Source

Liao M.,Huazhong University of Science and Technology | Li A.,Huazhong University of Science and Technology | Chen C.,Huazhong University of Science and Technology | Ouyang H.,Jiangxi University of Traditional Chinese Medicine | And 4 more authors.
Journal of chromatography. A | Year: 2015

Shikonin, shikonofuran and their derivatives are the main bioactive components of Zicao, a traditional Chinese herbal medicine prepared with the dried roots of Lithospermum erythrorhizon, Arnebia euchroma or Arnebia guttata. However, approaches on the systematic discovery and identification of shikonins and shikonofurans, especially unknown ones, are still not available. To address this issue, the gas-phase CID-fragmentation routes for the shikonins and shikonofurans were established by using ESI-QTOF-MS in the negative ion mode and low-energy collision induced dissociation tandem mass spectrometry (CID-MS/MS) in this study using seventeen standards. As a result, diagnostic product ions for rapid discovery and classification of shikonins and shikonofurans were determined. In addition, various mobile phase compositions and UHPLC elution programs were evaluated to achieve optimal separation efficiency and detection response of these types of analytes. Based on these findings, an integral approach using UHPLC-ESI-QTOF-MS and CID-MS/MS analyses together with a novel two steps data mining strategy was developed for systematic analysis of shikonins and shikonofurans in complex samples. Consequently, 58 compounds including 32 novel ones were efficiently discovered and identified from the crude extract of Zicao. Moreover, comparative analyses of the 58 chemical components in three Zicao species including Lithospermum erythrorhizon, Arnebia euchroma and Arnebia guttata samples were conducted using the established analytical method, which can be instructive for future utilization of Zicao and its related medicinal products. Copyright © 2015 Elsevier B.V. All rights reserved. Source

Gan Y.,Huazhong University of Science and Technology | Zhang Y.,Huazhong University of Science and Technology | Li A.,Huazhong University of Science and Technology | Song C.,Huazhong University of Science and Technology | And 4 more authors.
Phytochemical Analysis | Year: 2015

Introduction Systematic analyses of naphthoquinones in Juglans cathayensis have not yet been reported. It is very challenging to identify naphthoquinones with various structural diversities, especially those at trace levels. Objective To develop an efficient analytical approach for systematic discovery and identification of naphthoquinones in Juglans cathayensis. Methodology A novel four-step approach was evaluated by utilizing various scan functions of liquid chromatography-triple quadrupole-linear ion trap mass spectrometry (LC-QTRAP-MS/MS) and liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS) along with data mining strategies. First, MS/MS fragmentation behaviors of naphthoquinones were investigated. Second, multiple ion monitoring triggered enhanced product ion scan (MIM-EPI) with specified ions was conducted to identify targeted naphthoquinones. Third, other scan functions of QTRAP-MS/MS and data mining strategies were explored to identify untargeted naphthoquinones. Fourth, structural rationalization and confirmation of naphthoquinones were performed using QTOF-MS/MS via its accurate mass measurement and MS/MS fragmentation functions. Results Optimal scan methods and data mining strategies using QTRAP-MS/MS were obtained for identification of targeted and untargeted naphthoquinones. Consequently, 48 naphthoquinones including 24 novel ones were identified or tentatively identified from Juglans cathayensis. Conclusion A novel four-step approach for efficient discovery and identification of naphthoquinones was developed by exploring various scan functions of current LC-MS/MS technologies and data mining strategies, providing an example for systematic characterization of certain classes of phytochemicals, especially trace analytes in complex samples. Copyright © 2015 John Wiley & Sons, Ltd. Source

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