A flavonol glycoside, isolated from roots of Panax notoginseng, reduces amyloid-beta-induced neurotoxicity in cultured neurons: signaling transduction and drug development for Alzheimer's disease.
A Radix Notoginseng flavonol glycoside (RNFG), quercetin 3-O-beta-D-xylopyranosyl-beta-D-galactopyranoside, was isolated from roots of Panax notoginseng. Among different biological properties tested, RNFG possessed a strong activity in preventing amyloid-beta (Abeta)-induced cell death. In an in vitro assay, RNFG inhibited the aggregation of Abeta in a dose-dependent manner. Moreover, application of RNFG in cultured cortical neurons, or PC12 cells, reduced the Abeta-induced cell death in time- and dose-dependent manners, with the suppression of Abeta-induced DNA fragmentation and caspase-3 activation. In cultured neurons, the pre-treatment of RNFG abolished the increase of Ca(2+) mobilization triggered by Abeta. The neuroprotective properties of RNFG required a specific sugar attachment within the main chemical backbone because the flavonol backbone by itself did not show any protective effect. In memory impairment experiments using the passive avoidance task, the administration of RNFG reduced brain damage in scopolamine-treated rats. These results therefore reveal a novel function of Radix Notoginseng and its flavonol glycoside that could be very useful in developing food supplements for the prevention, or potential treatment, of Alzheimer's disease.
Choi
Roy C Y
RC
Department of Biology, The Hong Kong University of Science and Technology, Clear Water Bay Road, Hong Kong.
Zhu
Judy T T
JT
Leung
K Wing
KW
Chu
Glanice K Y
GK
Xie
Heidi Q
HQ
Chen
Vicky P
VP
Zheng
Ken Y Z
KY
Lau
David T W
DT
Dong
Tina T X
TT
Chow
Peter C Y
PC
Han
Yi-Fan
YF
Wang
Zheng-Tao
ZT
Tsim
Karl W K
KW
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000187:drug effects* / Q000378:metabolism* / Q000633:toxicity*; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D044948:Flavonols / Q000494:pharmacology* / Q000627:therapeutic use*; D006027:Glycosides / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D053723:Panax notoginseng; D008517:Phytotherapy / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
D016229:Amyloid beta-Peptides; D044948:Flavonols; D006027:Glycosides; D018696:Neuroprotective Agents