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

Yih-Fung Chen,Jia-Mao Gao,Fang-Rong Chang,Yu-Ting Tseng,Yi-Ching Lo,Ferenc Fülöp,Sheng-Nan Wu,Zhi-Yao Liao

doi:10.3390/molecules25122907

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

Highlights

We evaluated the effects of AN07 on nuclear factor erythroid 2-related factor 2 (Nrf2), which is a key transcription factor that regulates the expression of proteins involved in maintaining cellular redox anddensitometry counteracting oxidative damages In LPS-stimulated
Chalcones are a group of aromatic enones that belong to the flavonoid family and have been widely
Chalcones are a group of aromatic activities enones that to the flavonoid family and have been investigated for various pharmacological suchbelong as anti-tumor, antioxidant, anti-inflammatory, widely investigated for various pharmacological activities such occurring as anti-tumor, antioxidant, antianti-diabetic, and neuroprotective effects [2,3]

Summary

Introduction

A subclass of open-chain flavonoids that be in many naturally occurring compounds or manufactured synthetically [1]. Chalcones are regarded found in many naturally occurring compounds or manufactured synthetically [1]. As a result of their simple chemistry and convenient synthesis, many chalcone derivatives drug discovery [1]. As a result of their simple chemistry and convenient synthesis, many chalcone have been prepared and exert a broad spectrum of spectrum activities such as anti-inflammatory, antioxidant, derivatives have been prepared and exert a broad of activities such as anti-inflammatory, anti-tumor, and neuroprotective activities in different systems [2,3]. Some antioxidant,anti-microbial, anti-tumor, anti-microbial, and neuroprotective activities biological in different biological systems clinical trials have shown that compounds with the chalcone skeleton can reach sufficient plasma [2,3]. Some clinical trials have shown that compounds with the chalcone skeleton can reach sufficient concentrations withoutwithout causingcausing significant toxicities [2,4,5].[2,4,5]

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Results

Conclusion