Isoliquiritigenin Attenuates Atherogenesis in Apolipoprotein E-Deficient Mice

Abstract

Isoliquiritigenin (ISL) exhibits antioxidation and anti-inflammation activity. We sought to investigate the effects and mechanism of ISL on the development of atherosclerotic lesions in apolipoprotein E-deficient (apoE−/−) mice. Firstly, we determined that ISL reduced the mRNA levels of inflammatory factors interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and monocyte chemotactic protein-1 (MCP-1), while it increased the expression of several lipoprotein-related genes in peritoneal macrophages treated with lipopolysaccharide (LPS). ISL also enhanced peroxisome proliferator-activated receptor gamma (PPARγ) protein levels and reversed the changes of ATP-binding cassette transporter A (ABCA1) and cluster of differentiation 36 (CD36) in macrophages treated with oxidative low-density lipoprotein (ox-LDL). Then, in an in vivo study, female apoE−/− mice were fed a Western diet with ISL (0, 20, 100 mg/kg/day) added for 12 weeks. We found that ISL decreased the plasma cholesterol levels of very low-density lipoprotein (VLDL)/LDL, promoted plasma superoxide dismutase (SOD) and paraoxonase-1 (PON1) activities, and decreased plasma IL-6, TNF-α, and MCP-1 levels. Moreover, ISL significantly reduced the atherosclerotic lesions and hepatic steatosis in apoE−/− mice. In the liver, ISL altered the expression of several key genes (such as SRBI, ABCA1, ABCG8, PPARγ, and FASN) involving cholesterol-selective uptake and excretion into bile, triglyceride (TG) biosynthesis, and inflammation. These results suggest that the atheroprotective effects of ISL are due to the improvement of lipid metabolism, antioxidation, and anti-inflammation, which involve PPARγ-dependent signaling.

Isoliquiritigenin Inhibits IL-1β-Induced Production of Matrix Metalloproteinase in Articular Chondrocytes

“…It has diverse biological activities including anti-allergic, 12 anti-angiogenesis, 13 anti-tumor growth, 14 and anti-inflammation. 15 , 16 , 17 , 18 For the anti-inflammatory activity, ISL has been reported to inhibit LPS-induced nuclear factor κB (NF-κB) activation 16 and MAPK activation. 18 , 19 IL-1β can activate NF-κB and induce MMPs production, 20 , 21 playing an essential role in OA pathophysiology.…”

Dietary Isoliquiritigenin at a Low Dose Ameliorates Insulin Resistance and NAFLD in Diet-Induced Obesity in C57BL/6J Mice

“…ILG inhibits lipid accumulation and inhibits the insulin-signaling pathway through protein-tyrosine phosphatase 1B activation, a negative regulator of the insulin signaling cascade in 3T3-L1 cells [ 13 ]. ILG also ameliorates plasma lipid levels, inhibits oxidative stress and inflammation, and attenuates atherosclerosis in apolipoprotein E-deficient mice [ 14 ]. ILG ameliorates caerulein-induced acute pancreatitis in ICR mice by decreasing oxidative stress injury of the pancreatic tissue, and increasing the proteins expression of Nrf2/HO-1 [ 15 ].…”

Isoliquiritigenin Induces Autophagy and Inhibits Ovarian Cancer Cell Growth

“…Isoliquiritigenin (ISL), a natural flavonoid isolated from the root of the licorice plant ( Glycyrrhiza uralensis ), has a chalcone structure (4, 20, 40-trihydroxychalcone) [ 5 ]. Recently, ISL has been increasingly recognized to possess cancer-preventive and -suppressive activities such as anti-inflammatory [ 6 ], antioxidant [ 7 ], anti-platelet aggregation [ 8 ], atheroprotective [ 9 ], and estrogenic effects [ 10 ]. ISL exerts its antitumor effects by altering multiple molecular targets and regulating apoptotic and autophagic activities [ 11 , 12 ].…”