期刊
PLANTA MEDICA
卷 76, 期 9, 页码 863-868出版社
GEORG THIEME VERLAG KG
DOI: 10.1055/s-0029-1240801
关键词
Callistemon lanceolatus; Myrtaceae; beta-amyloid; 4 ',5dihydroxy-6,8-dimethyl-7-methoxyflavanone; C-methylflavonoids; apoptosis; PC12 cells
资金
- Korean Ministry of Education, Science and Technology [2009-009-1414]
Increased beta-amyloid (A beta) production and its aggregation to the oligomeric state is considered to be a major cause of Alzheimer's disease (AD). Therefore, reducing A beta-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 A beta were evaluated using PC12 cells. To evaluate the effects of A beta 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 A beta-induced toxicity. In particular, compound 1 showed the most promising neuroprotective effect with an ED50 value of 6.7 mu M in terms of decreasing A beta-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 A beta-induced apoptotic cell death.
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