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

Abstract

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 gp91phox 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-IκBα) 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-γ (PPARγ) 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-GSK3β, 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 proteins parkin, pink1, and DJ-1. These findings suggest that AN07 possesses the potentials to be an anti-inflammatory, antioxidant, and neuroprotective agent

Isobornylchalcones as Scaffold for the Synthesis of Diarylpyrazolines with Antioxidant Activity

“…Previously it has been reported that 3-(3,5-di-tert-butyl-4-hydroxyphenyl)-5-(multi-substituted-4-hydroxyphenyl)-2-pyrazoli nes showed significant human LDL-antioxidant activities (Figure 1) [25]. These results demonstrated that bulky di-tert-butyl groups contribute to higher activity by creating It was demonstrated that synthetic chalcone derivative 2-hydroxy-4 -methoxychalcone (AN07) potentially has anti-atherosclerosis effects, as well as antioxidant, anti-inflammatory, and neuroprotective effects [11]. Some prenylchalcones are isolated from hops and beer and exhibit antioxidant effects, modulate metabolism of carcinogens by inhibition of distinct phase 1 metabolic enzymes and activation of phase 2 detoxifying enzymes, and display anti-inflammatory properties [12].…”

“…[5][6][7][8][9][10]. It was demonstrated that synthetic chalcone derivative 2-hydroxy-4′-methoxychalcone (AN07) potentially has anti-atherosclerosis effects, as well as antioxidant, anti-inflammatory, and neuroprotective effects [11]. Some prenylchalcones are isolated from hops and beer and exhibit antioxidant effects, modulate metabolism of carcinogens by inhibition of distinct phase 1 metabolic enzymes and activation of phase 2 detoxifying enzymes, and display anti-inflammatory properties [12].…”

Iron Oxide Nanoparticles Combined with Cytosine Arabinoside Show Anti-Leukemia Stem Cell Effects on Acute Myeloid Leukemia by Regulating Reactive Oxygen Species

“…Nevertheless, both gp91-phox and SOD1 are related with the regulation of ROS level and oxidative stress. 47–49 Therefore, we further detected the expression levels of gp91-phox and SOD1 by Western blot. Figure 3A shows that the expression of gp91-phox was markedly increased in the Non-LSCs treated with IONPs, particularly in the Non-LSCs treated with IONPs plus Ara-C; the difference between the IONPs and IONPs plus Ara-C was statistically significant.…”

Research Progress on Natural Product Ingredients’ Therapeutic Effects on Parkinson’s Disease by Regulating Autophagy

“…In terms of regulating gene expression, the LIMK1 gene could not only participate in regulating synaptic remodeling and cytoskeleton stability of hippocampal neurons but also affect neuron migration by regulating Cofilin [ 108 ]. The SNCA gene was responsible for encoding the α -syn protein, whose mutation, duplication, or triplet could lead to autosomal dominant PD [ 109 ].…”