C-Methylflavonoids Isolated from Callistemon lanceolatus Protect PC12 Cells against Aβ-Induced Toxicity

Abstract

Increased beta-amyloid (Aβ) production and its aggregation to the oligomeric state is considered to be a major cause of Alzheimer's disease (AD). Therefore, reducing Aβ-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 Aβ were evaluated using PC12 cells. To evaluate the effects of Aβ 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 Aβ-induced toxicity. In particular, compound 1 showed the most promising neuroprotective effect with an ED₅₀ value of 6.7 µM in terms of decreasing Aβ-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 Aβ-induced apoptotic cell death.

Key words

Callistemon lanceolatus - Myrtaceae - β‐amyloid - 4′,5‐dihydroxy‐6,8‐dimethyl‐7‐methoxyflavanone - C‐methylflavonoids - apoptosis - PC12 cells

References

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