Novel quercetin-3-O-glucoside eicosapentaenoic acid ester ameliorates inflammation and hyperlipidemia

Abstract

Quercetin, a major flavonol, present abundantly in apples and onions, is widely studied for ameliorating metabolic syndrome abnormalities. However, quercetin is mainly present in plant food in the form of quercetin glycosides and has been reported for poor gastrointestinal absorption. The present study was designed with the purpose of imparting a lipophilic property to quercetin-3-O-glucoside (QG) by its acylation with eicosapentaenoic acid (EPA) and to study the influence of eicosapentaenoic acid ester of quercetin-3-O-glucoside (QE) on hyperlipidemia and inflammation in vivo and in vitro. QE was more effective in reducing the production of tumor necrosis factor-alpha (TNF-α), prostaglandin 2 (PGE2), cyclo-oxygenase (COX)-2 levels and nuclear expression of nuclear factor-kappa B (NF-кB) compared to the parent compounds (QG and EPA) and commercial drugs, after lipopolysaccharides (LPS) induced inflammation in THP-1 derived macrophages. Serum high-density lipoprotein (HDL)-cholesterol was significantly higher and hepatic total cholesterol concentration was lower in the rats fed high-fat diet supplemented with QE, compared to the high-fat diet with inflammation (HFL). The serum concentrations of C-reactive protein (CRP), interleukin (IL)-6, and interferon-gamma (IFN-γ) were significantly lower in QE treatment group than HFL group. EPA conjugated flavonol, QE, had significant anti-inflammatory and hypolipidemic properties and may be effective for the treatment of obesity-related disorders.

Biocatalytic Synthesis of Flavonoid Esters by Lipases and Their Biological Benefits

“…Serum HDL cholesterol was higher and hepatic total cholesterol was lower in rats fed with high-fat diet supplemented with acylated quercetin. Furthermore, serum concentrations of C-reactive protein (CRP), interleukin-6, and interferon-gamma (IFN-γ) were significantly lower in the group fed with the diet supplemented with acylated isoquercitrin compared to the group fed with a high-fat diet [107].…”

Efficiency comparison of PGBR extract and γ‐oryzanol in antioxidative stress and anti‐inflammatory properties against metabolic syndrome

“…Macrophage and T cells that infiltrate to adipose tissue induce inflammatory responses through IFN‐γ secretion (Prandota, ; Sadeghi et al, ). In addition, enzymes, such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX‐2) promote inflammation (Lee, Ha, Cho, & Choi, ); the metabolites NO and PGE 2 induce more oxidative stress, and further disrupt insulin function in cells (Lee et al, , ; Sekhon‐Loodu et al, ). Oxidative stress produces ox‐LDL and MDA, which stimulates lipid peroxidation (Kelany, Hakami, & Omar, ; Reverri et al, ).…”

Long Chain Fatty Acid Esters of Quercetin-3-O-glucoside Attenuate H2O2-induced Acute Cytotoxicity in Human Lung Fibroblasts and Primary Hepatocytes

“…Similarly, acylation of phloridzin and Q3G with long chain fatty acids provided anti-proliferative properties to the polyphenol compound as tested hepatocellular carcinoma HepG2 cells [26,27]. Acylation of flavonoids also provided enhanced anti-inflammatory function in lipopolysaccharide-induced inflammation in THP-1 differentiated macrophages [28,29]. Antioxidant activity of chlorogenic acid and its methyl, butyl, octyl, dodecyl and hexadecyl esters towards mitochondrial ROS generated in a ROS-overexpressing fibroblast cell line was investigated and long chain esters were found to be more effective in scavenging ROS [30].…”