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Pinocembrin protects against beta‐amyloid‐induced toxicity in neurons through inhibiting RAGE‐independent signaling pathways and regulating mitochondrion‐mediated apoptosis (877.4)
Author(s) -
Liu Rui,
Zhou Dan,
Zhang Li,
Zhang Li,
Zhang Tiantai,
Du Guanhua
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.877.4
Subject(s) - pinocembrin , rage (emotion) , neuroprotection , pharmacology , glycation , amyloid beta , mitochondrion , neurodegeneration , downregulation and upregulation , chemistry , neuroscience , medicine , biology , microbiology and biotechnology , receptor , biochemistry , disease , flavonoid , gene , antioxidant
Amyloid‐β (Aβ) peptides accumulate in the brain and initiate a cascade of pathological events in Alzheimer’s disease (AD). The receptor for advanced glycation end products (RAGE) has been implicated to mediate Aβ‐induced perturbations in AD. Pinocembrin was approved by the SFDA of China for clinical use for stroke patients and evidenced with neuroprotection against Aβ‐induced toxicity, but the therapeutic role and mechanism are not ascertained. Here, we report that pinocembrin improves cognition and protects neuron against Aβ‐mediated toxicity. Oral treatment of pinocembrin for 8 days improved cognitive function, preserved ultrastructural neuropils and decreased neurodegeneration in Aβ‐treated mice. Pinocembrin did not provide sufficient effect on inhibiting Aβ production. However, it inhibited the upregulation of RAGE transcripts and protein expression both in vivo and in vitro, and then, markedly depressed the activation of MAPK pathways and the downstream NF‐κB inflammatory response subsequent to Aβ‐RAGE interaction. In addition, pinocembrin alleviated mitochondrial dysfunction, and regulated mitochondrion‐mediated apoptosis. In conclusion, pinocembrin showed cognitive improvement and neuronal protection in AD models. The mechanisms were illustrated on RAGE‐dependent transduction inhibition and mitochondrion protection. It appears to be a promising candidate for the prevention and therapy of AD. Grant Funding Source : National Natural Science Foundation of China (No. 81102830)