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Synthesis and biological evaluation of 8-substituted and deglucuronidated scutellarin and baicalin analogues as antioxidant responsive element activators

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Abstract

Flavonoids are important bioactive dietary compounds, which are proved to be antioxidant responsive element (ARE) activators to defend against electrophilic toxicants and oxidative stress. The activators induce ARE gene transcription through Nrf2 factor, a major transcriptional stimulator of cytoprotective genes, relieved from a Keap1 complex. In this report, based on the structures of two flavonoids, scutellarin and baicalin, which are extracted from two common Chinese plants Dengzhanhua (Erigeron breviscapus (vant) Hand-Mazz) and Huangqin (Scutellaria baicalensis Georigi), respectively, we synthesized several 8-substituted and deglucuronidated analogues and identified the ARE activation effects of these flavonoids. We found that the Baicalin, deglucurnonidated Baicalin and diaza cyclopenta derivative were more active. Their dose-dependent upregulation activities of ARE and NQO1 and induction effects of Nrf2 were testified. The results presented that these three analogues had good upregulation effects on ARE, and they could be potentially utilized in relieving oxidative stress, upon further neuroprotective tests.

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Authors and Affiliations

  1. Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Ministry of Education, Tsinghua University, Beijing, 100084, China

    Ping Yang & ChangMei Cheng

  2. Academy of Military Medical Sciences, Beijing, 100850, China

    XiangZhen Kong, ChangYan Li & XiaoMing Yang

  3. Jiangsu Simcere Pharmaceutical Research Institute, Nanjing, 210042, China

    Xing’E Zhao

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  1. Ping Yang
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  2. XiangZhen Kong
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  3. ChangMei Cheng
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  4. ChangYan Li
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  5. XiaoMing Yang
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Correspondence to ChangMei Cheng.

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Yang, P., Kong, X., Cheng, C. et al. Synthesis and biological evaluation of 8-substituted and deglucuronidated scutellarin and baicalin analogues as antioxidant responsive element activators. Sci. China Chem. 54, 1565–1575 (2011). https://doi.org/10.1007/s11426-011-4361-4

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  • DOI: https://doi.org/10.1007/s11426-011-4361-4

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