Inhibition of glycogen synthase kinase by curcumin: Investigation by simulated molecular docking and subsequent in vitro/in vivo evaluation

被引：78

作者：

Bustanji, Yasser ^{[1
]}

Taha, Mutasem O. ^{[1
]}

Almasri, Ihab M. ^{[1
]}

Al-Ghussein, Mohamed A. S. ^{[1
]}

Mohammad, Mohammad K. ^{[1
]}

Alkhatib, Hatim S. ^{[1
]}

机构：

[1] Univ Jordan, Dept Biopharmaceut & Clin Pharm, Fac Pharm, Amman 11942, Jordan

来源：

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2009年 / 24卷 / 03期

关键词：

Curcumin; glycogen synthase kinase; docking simulation; diabetes; inflammation; NF-KAPPA-B; CHEMOPREVENTIVE AGENT; ALZHEIMERS-DISEASE; GSK-3; INHIBITORS; KINASE-3-BETA; ACTIVATION; CELLS; BINDING; HYDROXYCHLOROQUINE; ACETYLTRANSFERASE;

D O I：

10.1080/14756360802364377

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Curcumin was investigated as an inhibitor of glycogen synthase kinase-3 beta (GSK-3 beta) in an attempt to explain some of its interesting multiple pharmacological effects, such as its anti-diabetic, anti-inflammatory, anti-cancer, anti-malarial and anti-alzheimer's properties. The investigation included simulated docking experiments to fit curcumin within the binding pocket of GSK-3 beta followed by experimental in vitro and in vivo validations. Curcumin was found to optimally fit within the binding pocket of GSK-3 beta via several attractive interactions with key amino acids. Experimentally, curcumin was found to potently inhibit GSK-3 beta (IC50 = 66.3 nM). Furthermore, our in vivo experiments illustrated that curcumin significantly increases liver glycogen in fasting Balb/c mice. Our findings strongly suggest that the diverse pharmacological activities of curcumin are at least partially mediated by inhibition of GSK-3 beta.

引用

页码：771 / 778

页数：8

共 49 条

[1]

GSK-3 inhibitors: Discoveries and developments [J].