Probing antioxidant activity of 2¡ä-hydroxychalcones: Crystal and molecular structures, in?vitro antiproliferative studies and in?vivo effects on glucose regulation
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- 作者：Miriam Rossi ; Francesco Caruso ; Erica J. Crespi ; Jens Z. Pedersen ; Gail Nakano ; Michelle Duong ; Celia Mckee ; Sharon Lee ; Manasi Jiwrajka ; Charles Caldwell ; Francis Baffour ; Dylan Alex Karlin ; Genevieve Lidoff ; Stefano Leone ; Valentina Balducci ; Jaroslav Miler ; S ; ra Incerpi
- 关键词：Chalcone antioxidant ; Free radical scavenger ; THP-1 monocytes ; L-6 myoblasts ; Glucose regulation
- 刊名：Biochimie
- 出版年：2013
- 出版时间：October, 2013
- 年：2013
- 卷：95
- 期：10
- 页码：1954-1963
- 全文大小：1636 K
文摘
In order to better understand the antioxidant behavior of a series of polyphenolic 2¡ä-hydroxychalcones, we describe the results of several chemical and biological studies, in?vitro and in?vivo. Single crystal X-ray methods elucidated their molecular structures and important intermolecular interactions such as H-bonding and molecular stacking in the crystal structures that contribute to our knowledge in explaining antioxidant activity. The results of experiments using the 1,1-diphenyl-2-dipicrylhydrazyl (DPPH) UV-vis spectroscopic method indicate that a hydroxyl group in position 5¡ä induces the highest antioxidant activity. Consequently, 2,2¡ä,5¡ä-trihydroxychalcone was selected for further study in?vitro towards ROS scavenging in L-6 myoblasts and THP-1 human monocytes, where it shows an excellent antioxidant activity in a concentration range lower than that reported by most studies of related molecules. In addition, this chalcone shows a very selective activity: it inhibits the proliferation of leukemic cells, but it does not affect the normal L-6 myoblasts and human fibroblasts. In studying 2,2¡ä,5¡ä-trihydroxychalcone's effect on weight gain and serum glucose and insulin levels in Zucker fatty (fa?/fa?) rats we found that supplementing the diet with a 10?mg/kg dose of this chalcone (3 times weekly) blunted the increase in glucose that co-occurs with weight gain over the 6-week treatment period. It is concluded that 2,2¡ä,5¡ä-trihydroxychalcone has the potential to serve as a protective agent for some debilitating diseases.