C-methylflavonoids isolated from Callistemon lanceolatus protect PC12 cells against Abeta-induced toxicity.
Increased beta-amyloid (Abeta) production and its aggregation to the oligomeric state is considered to be a major cause of Alzheimer's disease (AD). Therefore, reducing Abeta-induced neurotoxicity could provide a suitable means of prevention or intervention in the disease course of AD. The neuroprotective effects of isolates from Callistemon lanceolatus DC. (Myrtaceae) against Abeta were evaluated using PC12 cells. To evaluate the effects of Abeta on apoptotic cell death and the effects of Bcl-2 family proteins and caspase-3, TUNEL assays and Western blotting were performed, respectively. Substantial fractionation and purification of the EtOAc-soluble extract of the aerial parts of C. lanceolatus afforded six flavonoids, 4',5-dihydroxy-6,8-dimethyl-7-methoxyflavanone (1), eucalyptin (2), 8-demethyleucalyptin (3), sideroxylin (4), syzalterin (5), and quercetin (6). Compounds 1, 5, and 6 were found to protect PC12 cells effectively against Abeta-induced toxicity. In particular, compound 1 showed the most promising neuroprotective effect with an ED (50) value of 6.7 microM in terms of decreasing Abeta-induced apoptotic cell death, and this was accompanied by a decrease in caspase-3 activation and an increase in Bcl-2/Bax ratio. These results suggest that compound 1 could be developed as a candidate anti-AD agent due to its attenuation of Abeta-induced apoptotic cell death.
Park
So-Young
SY
Environmental Toxico-Genomic & Proteomic Center, College of Medicine, Korea University, Seoul, Korea.
Lim
Ji-Youn
JY
Jeong
Wonsik
W
Hong
Seong Su
SS
Yang
Young Taek
YT
Hwang
Bang Yeon
BY
Lee
Dongho
D
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism*; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D027822:Myrtaceae / Q000737:chemistry*; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D016716:PC12 Cells; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats
D016229:Amyloid beta-Peptides; D005419:Flavonoids; D018696:Neuroprotective Agents; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D053148:Caspase 3