Deoxygedunin, a Natural Product with Potent Neurotrophic Activity in Mice

作者：Jang Sung Wuk^*; Liu Xia; Chan Chi Bun; France Stefan A; Sayeed Iqbal; Tang Wenxue; Lin Xi; Xiao Ge; Andero Raul; Chang Qiang; Ressler Kerry J; Ye Keqiang

来源：PLos One, 2010, 5(7): e11528.

DOI：10.1371/journal.pone.0011528

Gedunin, a family of natural products from the Indian neem tree, possess a variety of biological activities. Here we report the discovery of deoxygedunin, which activates the mouse TrkB receptor and its downstream signaling cascades. Deoxygedunin is orally available and activates TrkB in mouse brain in a BDNF-independent way. Strikingly, it prevents the degeneration of vestibular ganglion in BDNF -/- pups. Moreover, deoxygedunin robustly protects rat neurons from cell death in a TrkB-dependent manner. Further, administration of deoxygedunin into mice displays potent neuroprotective, anti-depressant and learning enhancement effects, all of which are mediated by the TrkB receptor. Hence, deoxygedunin imitates BDNF's biological activities through activating TrkB, providing a powerful therapeutic tool for treatment of various neurological diseases.

• 出版日期2010-7-13