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Hydroxycinnamic Acid from Corncob and Its Structural Analogues Inhibit Aβ40 Fibrillation and Attenuate Aβ40-Induced Cytotoxicity
journal contribution
posted on 2020-08-06, 22:19 authored by Sijia Hao, Xia Li, Ailing Han, Yayu Yang, Xiaoyu Luo, Guozhen Fang, Hao Wang, Jifeng Liu, Shuo WangThe
aggregation of amyloid-β protein (Aβ) is deemed
a vital pathological feature of Alzheimer’s disease (AD). Hence,
inhibiting Aβ aggregation is noticed as a major tactic for the
prevention and therapy of AD. Hydroxycinnamic acid, as a natural phenolic
compound, is widely present in plant foods and has several biological
activities including anti-inflammation, antioxidation, and neuroprotective
effects. Here, it was found that hydroxycinnamic acid and its structural
analogues (3-hydroxycinnamic acid, 2-hydroxycinnamic acid, cinnamic
acid, 3,4-dihydroxycinnamic acid, 2,4-dihydroxycinnamic acid, and
3,4,5-trihydroxycinnamic acid) could inhibit Aβ40 fibrillogenesis
and reduce Aβ40-induced cytotoxicity in a dose-dependent manner.
Among these small molecules investigated, 3,4,5-trihydroxycinnamic
acid is considered to be the most effective inhibitor, which reduces
the ThT fluorescence intensity to 30.79% and increases cell viability
from 49.47 to 84.78% at 200 μM. Also, the results with Caenorhabditis elegans verified that these small
molecules can ameliorate AD-like symptoms of worm paralysis. Moreover,
molecular docking studies showed that these small molecules interact
with the Aβ40 mainly via hydrogen bonding. These results suggest
that hydroxycinnamic acid and its structural analogues could inhibit
Aβ40 fibrillogenesis and the inhibition activity is enhanced
with the increase of phenolic hydroxyl groups of inhibitors. These
small molecules have huge potential to be developed into novel aggregation
inhibitors in neurodegenerative disorders.