The Antioxidant, Anti-Inflammatory, and Neuroprotective Properties of the Synthetic Chalcone Derivative AN07

Chalcones belong to a class of biologically active polyphenolic natural products. As a result of their simple chemical nature, they are easily synthesized and show a variety of promising biological activities. 2-Hydroxy-4 '-methoxychalcone (AN07) is a synthetic chalcone derivate with potential...

Teljes leírás

Elmentve itt :
Bibliográfiai részletek
Szerzők: Chen Yih-Fung
Wu Sheng-Nan
Gao Jia-Mao
Liao Zhi-Yao
Tseng Yu-Ting
Fülöp Ferenc
Chang Fang-Rong
Lo Yi-Ching
Dokumentumtípus: Cikk
Megjelent: 2020
Sorozat:MOLECULES 25 No. 12
doi:10.3390/molecules25122907

mtmt:31500739
Online Access:http://publicatio.bibl.u-szeged.hu/19467
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520 3 |a Chalcones belong to a class of biologically active polyphenolic natural products. As a result of their simple chemical nature, they are easily synthesized and show a variety of promising biological activities. 2-Hydroxy-4 '-methoxychalcone (AN07) is a synthetic chalcone derivate with potential anti-atherosclerosis effects. In this study, we demonstrated the novel antioxidant, anti-inflammatory, and neuroprotective effects of AN07. In RAW 264.7 macrophages, AN07 attenuated lipopolysaccharide (LPS)-induced elevations in reactive oxygen species (ROS) level and oxidative stress via down-regulating gp91(phox)expression and stimulating the antioxidant system of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) pathways, which were accompanied by increased glutathione (GSH) levels. Additionally, AN07 attenuated LPS-induced inflammatory factors, including NO, inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and phosphorylated inhibitor of nuclear factor kappa B-alpha (p-I kappa B alpha) in RAW 264.7 macrophages. However, the effects of AN07 on promoting nuclear Nrf2 levels and decreasing COX-2 expressions were significantly abrogated by the peroxisome proliferator-activated receptor-gamma (PPAR gamma) antagonist GW9662. In human dopaminergic SH-SY5Y cells treated with or without methylglyoxal (MG), a toxic endogenous by-product of glycolysis, AN07 up-regulated neurotrophic signals including insulin-like growth factor 1 receptor (IGF-1R),p-Akt,p-GSK3 beta, glucagon-like peptide 1 receptor (GLP-1R), and brain-derived neurotrophic factor (BDNF). AN07 attenuated MG-induced apoptosis by up-regulating the B-cell lymphoma 2 (Bcl-2) protein and down-regulating the cytosolic expression of cytochrome c. AN07 also attenuated MG-induced neurite damage via down-regulating the Rho-associated protein kinase 2 (ROCK2)/phosphorylated LIM kinase 1 (p-LIMK1) pathway. Moreover, AN07 ameliorated the MG-induced down-regulation of neuroprotective Parkinsonism-associated proteinsparkin,pink1, andDJ-1. These findings suggest that AN07 possesses the potentials to be an anti-inflammatory, antioxidant, and neuroprotective agent 
700 0 1 |a Wu Sheng-Nan  |e aut 
700 0 1 |a Gao Jia-Mao  |e aut 
700 0 1 |a Liao Zhi-Yao  |e aut 
700 0 1 |a Tseng Yu-Ting  |e aut 
700 0 1 |a Fülöp Ferenc  |e aut 
700 0 1 |a Chang Fang-Rong  |e aut 
700 0 1 |a Lo Yi-Ching  |e aut 
856 4 0 |u http://publicatio.bibl.u-szeged.hu/19467/1/molecules-25-02907.pdf  |z Dokumentum-elérés