title: Effects of naturally occurring compounds on fibril formation and oxidative stress of beta-amyloid.
abstract: Beta-amyloid (betaA)-induced oxidative toxicity on neuronal cells is a principal route in Alzheimer's disease (AD), and its toxicity occurs after fibril formation. Inhibitory or promoting effects of naturally occurring compounds on betaA fibril formation were evaluated. Among 214 tested compounds, curcuminoids, flavone type flavonoids, and naphthoquinones were shown to be potent inhibitors of betaA fibrilization. The addition of the curcuminoids, curcumin, demethoxycurcumin, and bisdemethoxycurcumin strongly inhibited betaA fibril formation. Flavonoids such as quercetin, rhamnetin, and fisetin strongly inhibited betaA fibril formation. Limonoids, cinnamic acids, and catechins enhanced fibril formation in vitro. Anthothecol possessed the most enhancing activity on fibril formation of the compounds tested. On the other hand, it was found that curcuminoids showed cytotoxicity with the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay and did not protect HT22 murine neuroblastoma cells from betaA(25-35) insult. Two flavone type flavonoids, morin and quercetin, exhibited no cytotoxicity and strongly protected HT22 murine neuroblastoma cells from betaA(25-35) oxidative attack. Conclusively, morin or quercetin could be a key molecule for the development of therapeutics for AD.
authors.affiliation: Digitalbiotech Inc., Sin Gil Dong 1227, An San City, Kyong Gi Do 425-839, Korea.
authors.forename: Hee
authors.initials: H
authors.lastname: Kim
authors.forename: Byeoung-Soo
authors.initials: BS
authors.lastname: Park
authors.forename: Kwang-Geun
authors.initials: KG
authors.lastname: Lee
authors.forename: Cheol Yong
authors.initials: CY
authors.lastname: Choi
authors.forename: Sung Sik
authors.initials: SS
authors.lastname: Jang
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Lee
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000737:chemistry*; D000818:Animals; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D051379:Mice; D009285:Naphthoquinones / Q000494:pharmacology*; D009447:Neuroblastoma; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D016229:Amyloid beta-Peptides; D005419:Flavonoids; D009285:Naphthoquinones; D003474:Curcumin