Jong-Min Han

In Vitro Antioxidant and Anti-inflammatory Activities of Jaceosidin from Artemisia princeps Pampanini cv. Sajabal

Oxidized low-density lipoprotein (oxLDL) plays a key role in the inflammatory processes of atherosclerosis. Jaceosidin isolated from the methanolic extracts of the aerial parts of Artemisia princeps Pampanini cv. Sajabal was tested for antioxidant and anti-inflammatory activities. Jaceosidin inhibited the Cu2+-mediated LDL oxidation with IC50 values of 10.2 μM in the thiobarbituric acid-reactive substances (TBARS) assay as well as the macrophage-mediated LDL oxidation. The antioxidant activities of jaceosidin were exhibited in the conjugated diene production, relative electrophoretic mobility, and apoB-100 fragmentation on copper-mediated LDL oxidation. Jaceosidin also inhibited the generation of reactive oxygen species (ROS) concerning in regulation of NF-κB signaling. And jaceosidin inhibited nuclear factor-kappa B (NF-κB) activity, nitric oxide (NO) production, and suppressed expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages.

ApoA-I mutants V156K and R173C promote anti-inflammatory function and antioxidant activities.

Background  Two mutants of apolipoprotein (apo) A‐I, V156K and A158E, showed markedly different structural and functional properties in lipid‐free and lipid‐bound states in the authors’ earlier report. The physiological activities of these mutants were compared with the wild‐type (WT) and R173C mutant using in vitro and in vivo experiments.

Ethanolic Extracts of Brassica campestris spp. rapa Roots Prevent High-Fat Diet-Induced Obesity via β3-Adrenergic Regulation of White Adipocyte Lipolytic Activity

The influence of ethanolic extracts of Brassica campestris spp. rapa roots (EBR) on obesity was examined in imprinting control region (ICR) mice fed a high-fat diet (HFD) and in 3T3-L1 adipocytes. The ICR mice used were divided into regular diet, HFD, EBR (50 mg/kg/day EBR administered orally), and orlistat (10 mg/kg/day orlistat administered orally) groups. The molecular mechanism of the anti-obesity effect of EBR was investigated in 3T3-L1 adipocytes as well as in HFD-fed ICR mice. In the obese mouse model, both weight gain and epididymal fat accumulation were highly suppressed by the daily oral administration of 50 mg/kg EBR for 8 weeks, whereas the overall amount of food intake was not affected. EBR treatment induced the expression in white adipocytes of lipolysis-related genes, including beta(3)-adrenergic receptor (beta(3)-AR), hormone-sensitive lipase (HSL), adipose triglyceride lipase, and uncoupling protein 2. Furthermore, the activation of cyclic AMP-dependent protein kinase, HSL, and extracellular signal-regulated kinase was induced in EBR-treated 3T3-L1 cells. The lipolytic effect of EBR involved beta(3)-AR modulation, as inferred from the inhibition by the beta(3)-AR antagonist propranolol. These results suggest that EBR may have potential as a safe and effective anti-obesity agent via the inhibition of adipocyte lipid accumulation and the stimulation of beta(3)-AR-dependent lipolysis.

Antiatherosclerotic Effects of Artemisia princeps Pampanini cv. Sajabal in LDL Receptor Deficient Mice

Antiatherosclerotic effects of ethanolic extracts of Artemisia princeps Pampanini cv. Sajabal (ESJ) were investigated in low-density lipoprotein receptor deficient (LDLR(-/-)) mice. The Western diet-induced high levels of total cholesterol and triglyceride were similar in the ESJ and control groups. However, circulating oxidized LDL was significantly decreased in the ESJ group (p < 0.05). ESJ also markedly decreased aortic expression levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta), and reduced the aortic lesion formation and macrophage accumulation by 36.7% (p < 0.05) and 43% (p < 0.01) in the control group, respectively. Additionally, ESJ inhibited atherogenic properties with cytokine-induced surface expression of cell adhesion molecules, chemokines, and monocyte adhesion to the human umbilical vein endothelial cells (HUVECs), and simultaneously suppressed nuclear factor-kappaB (NF-kappaB) activation. These results suggest that ethanolic extracts of Artemisia princeps Pampanini cv. Sajabal contributes to the antiatherosclerotic and anti-inflammatory activities in LDLR(-/-) mice.

A point mutant of apolipoprotein A-I, V156K, exhibited potent anti-oxidant and anti-atherosclerotic activity in hypercholesterolemic C57BL/6 mice.

In our previous study, two point mutants of apolipoprotein A-I, designated V156K and A158E, revealed peculiar characteristics in their lipid-free and lipid-bound states. In order to determine the putative therapeutic potential of these mutants, several in vitro and in vivo evaluations were conducted. In the lipid-free state, V156K showed more profound antioxidant activity against LDL oxidation than did the wildtype (WT) or A158E variants in an in vitro assay. In the lipid-bound state, V156K-rHDL showed an enhanced cholesterol delivery activity to HepG2 cells in a time-dependent manner, as compared to WT-rHDL, A158E-rHDL, and R173C-rHDL. We assessed the physiological activities of the mutants in circulation, using hypercholesterolemic mice (C57BL6/J). Palmitoyloleoyl phosphatidylcholine (POPC)-rHDL preparations containing each of the apoA-I variants were injected into the mice at a dosage of 30 mg of apoA-I/kg of body weight. Forty eight hours after injection, the sera of the V156K-rHDL injected group showed the most potent antioxidant abilities in the ferric acid removal assay. The V156K-rHDL- or R173C-rHDL-injected mice showed no atherosclerotic lesions and manifested striking increases in their serum apo-E levels, as compared to the mice injected with WT-rHDL or A158E-rHDL. In conclusion, V156K-rHDL exhibited the most pronounced antioxidant activity and anti-atherosclerotic activity, both in vitro and in vivo. These results support the notion that HDL-therapy may prove beneficial due to its capacity to induce accelerated cholesterol excretion, as well as its enhanced antioxidant and anti-inflammatory effects and lesion regression effect.

Soy-Leaf Extract Exerts Atheroprotective Effects via Modulation of Krüppel-Like Factor 2 and Adhesion Molecules

Soy-leaf extracts exert their cardioprotective effects by inducing endothelium-dependent vasodilation in the arteries, and they favorably modulate the serum lipid profile. In this study, we investigated the atheroprotective effects of an ethanol extract of soy leaf (ESL) in human umbilical vein endothelial cells (HUVECs) and high-cholesterol diet (HCD)-fed low-density lipoprotein receptor deficient (LDLR−/−) mice. ESL induced the expression of Krüppel-like factor 2 (KLF2), an endothelial transcription factor, and endothelial nitric oxide synthase (eNOS), and suppressed the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) through moderate inflammatory signal activation, not only in tumor necrosis factor-α (TNF-α)-stimulated HUVECs but also in 7-ketocholesterol (7-KC)-stimulated HUVECs. ESL supplementation reduced aortic lesion formation in Western diet-fed LDLR−/− mice by 46% (p < 0.01) compared to the HCD group. ESL also markedly decreased the aortic expression levels of VCAM-1, ICAM-1, monocyte chemotactic protein-1 (MCP-1), TNF-α, IL-6, IL-1β, matrix metallopeptidase 9 (MMP-9), and fractalkine, while the expression of KLF2 was significantly increased. These results suggest that ESL supplementation has potential for preventing HCD-induced atherosclerosis effectively.

Anti-atherosclerotic effect of a new synthetic functional oil containing mono- and diacylglycerol from corn oil.

Synthetic oil containing diacylglycerol and monoacylglycerol, called ‘functional oil’ (FO), was newly produced and evaluated for its putative anti-atherosclerotic potential by in vitro assays and in vivo test using hypercholesterolemic mice (C57BL/6). The FO revealed good inhibitory activities against both liver acyl-CoA:cholesterol acyltransferase and serum lipoprotein-associated phospholipase A2. The FO showed enhanced activities on lipoprotein interaction such as HDL particle rearrangement to produce different sizes of HDL species. In control mice, hypercholesterolemia was induced by consumption of high-cholesterol, high-fat (HCHF) diet that contained 1.25% cholesterol/15% fat/0.5% Na-cholate with or without 5% of corn oil. In experimental mice, 5% of the FO + HCHF diet was fed during the same period. After the 4-week administration of the diet, serum total cholesterol concentration of the FO-fed group decreased by 38 or 20% when compared to the HCHF diet control group or corn oil (99.9% of triacylglycerol) diet group, respectively. The percentage of HDL cholesterol to total cholesterol was 36% of HDL cholesterol in the FO-fed group, while the HCHF control group and corn oil-fed group showed 21 and 25%, respectively. These results indicate that the FO possesses a blood cholesterol-lowering effect in mouse model and inhibition effects against the atherogenic enzymes.

2′-Benzoyloxycinnamaldehyde Inhibits Tumor Growth in H-ras12V Transgenic Mice via Downregulation of Metallothionein

Cinnamaldehydes have been reported to induce apoptosis in human carcinomas through the generation of reactive oxygen species (ROS). 2′-benzoyloxycinnamaldehyde (BCA) has been reported to inhibit tumor formation in H-ras12V transgenic mice. To see the antitumor effects of BCA, BCA was administrated intraperitoneally (50 mg/kg) to H-ras12V transgenic mice for 3 wk, and it was found that the hepatic tumor volume and the total number of tumors were decreased in BCA-treated mice as compared to control H-ras12V transgenic mice. To identify possible target genes responsible for BCA antitumor effects in H-ras12V transgenic mice, cDNA microarray analyses were performed comparing gene expression between BCA treated and control transgenic mice. We found that 42 genes were downregulated, and 40 genes were upregulated in the BCA-treated transgenic mice. The downregulated genes included several genes involved in ROS regulation and immune response (aconitase, metallothionein-1, metallothionein-2, and purine nucleoside phosphorylase). The expression of ROS-related genes, metallothionein 1 and metallothionein 2, was decreased more than twofold with BCA treatment (P < 0.001). It was confirmed by RT-PCR and immunohistochemical analyses. The inhibition of tumor formation and growth in H-ras12V transgenic mice by BCA was mediated through inhibition of the expression of the ROS scavengers metallothionein 1 and metallothionein 2.