Kang-Yeol Yu

Schizandrin prevents damage of murine mesangial cells via blocking NADPH oxidase-induced ROS signaling in high glucose.

High glucose (HG) is the underlying factor contributing to long term complication of diabetes mellitus. Reactive oxygen species (ROS) have been postulated as a unifying mechanism for HG-induced complications. NADPH oxidase, producing superoxide anion, is the main source of ROS in diabetic nephropathy. In this study we report the inhibitory effect of schizandrin (Sch), an active ingredient of Fructus schisandrae, on HG-induced murine mesangial cells (MMCs) damage. Sch treatment significantly attenuated HG-induced proliferation and protein synthesis of MMCs in a dose dependent manner. The intracellular reactive oxygen species (ROS) level was also remarkably reduced by Sch as well as the enhanced NADPH oxidase activity, superoxide anion levels, NOX4 and p22phox protein expression, and phosphorylation of p47phox and p67phox. The phosphorylation level of mitogen activated kinase (MAPK) protein, phospho-Erk1/2 and -p38, and Akt was also significantly inhibited by Sch under HG condition. By using specific inhibitors, we found that Sch inhibits HG-induced mesangial cell proliferation and ECM overexpression via NADPH oxidase/PI3K-Akt-MAPK-dependent pathway in MMCs. Taken together; our demonstration of the ability of Sch to inhibit high glucose induced damage of MMCs has clinical implications in treatment of diabetic nephropathy.

Antibacterial activity of phytochemicals isolated from Atractylodes japonica against methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) has been emerging worldwide as one of the most important problems in communities and hospitals. Therefore, new agents are needed to treat acute oral infections from MRSA. In this study, antibacterial compounds from the roots of Atractylodes japonica (A. japonica) were isolated and characterized. The compounds were isolated from the root extracts using HPLC-piloted activity-guided fractionations. Four A. japonica compounds were isolated and identified as atractylenolide III (1), atractylenolide I (2), diacetylatractylodiol [(6E,12E)-tetradeca-6,12-diene-8,10-diyne-1,3-diol diacetate, TDEYA, 3). and (6E,12E)-tetradecadiene-8,10-diyne-1,3-diol (TDEA, 4), which was obtained by hydrolysis of TDEYA. The minimum inhibitory concentrations (MICs) was determined in the setting of clinical MRSA isolates. Compound 4 showed anti-MRSA activity with a MIC value of 4-32 μg/mL. The overall results provide promising baseline information for the potential use of the extract of A. japonica as well as some of the isolated compounds in the treatment of bacterial infections.

Decursin attenuates hepatic fibrogenesis through interrupting TGF-beta-mediated NAD(P)H oxidase activation and Smad signaling in vivo and in vitro.

AIMS We studied that a potent antifibrotic effect of decursin on in vivo liver damage model and the mechanism in inhibiting which transforming growth factor (TGF)-β1-induced human hepatic stellate cells (HSCs) activation. MAIN METHODS Liver injury was induced in vivo by intraperitoneal injection of carbon tetrachloride (CCl4) with or without decursin for 4weeks in mice. Human hepatic stellate cell line, an immortalized human HSC line, was used in in vitro assay system. The effects of decursin on HSC activation were measured by analyzing the expression of α-smooth muscle actin (α-SMA) and collagen I in liver tissue and human HSCs. KEY FINDINGS Decursin treatment significantly reduced the ratio of liver/body weight, α-SMA activation, and type I collagen overexpression in CCl4 treated mice liver. The elevated serum levels, including ALT, AST, and ALP, were also decreased by decursin treatment. Treatment of decursin markedly proved the generation of reactive oxygen species, NAD(P)H oxidase (NOX) protein (1, 2, and 4) upregulation, NOX activity, and superoxide anion production in HSCs by TGF-β1. It also significantly reduced TGF-β1-induced Smad 2/3 phosphorylation, nuclear translocation of Smad 4, and association of Smad 2/3-Smad 4 complex. Consistent with in vitro results, decursin treatment effectively blocked the levels of NOX protein, and Smad 2/3 phosphorylation in injured mice liver. SIGNIFICANCE Decursin blocked CCl4-induced liver fibrosis and inhibited TGF-β1-mediated HSC activation in vitro. These data demonstrated that decursin exhibited hepatoprotective effects on experimental fibrosis, potentially by inhibiting the TGF-β1 induced NOX activation and Smad signaling.

Antimicrobial Effects and Resistant Regulation of Magnolol and Honokiol on Methicillin-Resistant Staphylococcus aureus

The antimicrobial killing activity toward methicillin-resistant Staphylococcus aureus (MRSA) has been a serious emerging global issue. In a continuing search for compounds with antibacterial activity against several microorganisms including S. aureus and MRSA, an n-hexane extract of Magnolia officinalis was found to contain magnolol. This compound exhibited potent activity against S. aureus, standard methicillin-susceptible S. aureus (MSSA), and MRSA as well as clinical MRSA isolates. When combined with oxacillin, the antibacterial activities of magnolol and honokiol against the MRSA strain were increased compared to single treatment without antibiotics at 10 µg/mL and 25 µg/mL, respectively. These activities of magnolol and honokiol were dose dependent. Also, magnolol showed synergistic effects with oxacillin against 13 clinical isolates of MRSA. It was determined that magnolol and honokiol had a synergistic effect with oxacillin against MRSA strain. Furthermore, the magnolol inhibited the expression of the resistant genes, mecA, mecI, femA, and femB, in mRNA. We concluded that the antibacterial activity of magnolol against MRSA strain is more related to the mecIs pathway and components of the cell wall than mecR1. Therefore, the results obtained in this study suggest that the combination of magnolol and antibiotics could lead to the development of new combination antibiotics against MRSA infection.

Hypocholesterolemic Effects of Probiotic Mixture on Diet-Induced Hypercholesterolemic Rats

Growing evidence has indicated that supplementation with probiotics improves lipid metabolism. We aimed to investigate the beneficial effects of a probiotics mixture (PM) of three strains belonging to the species Bifidobacterium (B. longum, B. lactis, and B. breve) and two strains belonging to the species Lactobacillus (L. reuteri and L. plantarum) on cholesterol-lowering efficacy in hypercholesterolemic rats. A hypercholesterolemic rat model was established by feeding a high-cholesterol diet for eight weeks. To test the effects of PM on hypercholesterolemia, hypercholesterolemic rats were assigned to four groups, which were treated daily with low (1.65 × 109 cfu/kg), medium (5.5 × 109 cfu/kg), or high (1.65 × 1010 cfu/kg) doses of probiotic mixture or simvastatin for eight weeks. Significant reductions of serum total cholesterol (TC), triacylglycerol (TG), and low-density lipoprotein (LDL)-cholesterol levels, but increases of high-density lipoprotein (HDL)-cholesterol were observed after supplementation of PM in hypercholesterolemic rats. In PM-supplemented hypercholesterolemic rats, hepatic tissue contents of TC and TG also significantly decreased. Notably, the histological evaluation of liver tissues demonstrated that PM dramatically decreased lipid accumulation. For their underlying mechanisms, we demonstrated that PM reduced expressions of cholesterol synthesis-related proteins such as sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) in the liver. Taken together, these findings suggest that PM has beneficial effects against hypercholesterolemia. Accordingly, our PM might be utilized as a novel therapeutic agent for the management of hypercholesterolemia.

Anti-Inflammatory Effects of Oenanthe javanica Ethanol Extract and Its Fraction on LPS-Induced Inflammation Response

The present study examined the anti-inflammatory effects of Oenanthe javanica ethanol extract (OJE) and its fraction on the lipopolysaccharide (LPS)-induced inflammatory response in RAW 264.7 macrophage cells. OJE remarkably reduced protein expression of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX-2), resulting in inhibition of production of nitric oxide (NO). In order to identify the anti-inflammatory effects of bioactive fractions, OJE was fractionated into hexane, dichloromethane, ethyl acetate, and n-butanol fractions. The results show that the ethyl acetate and dichloromethane fractions reduced production of NO without cytotoxicity. Especially, the ethyl acetate fraction effectively reduced protein expression of iNOS and COX-2. Proinflammatory cytokine production was also reduced by ethyl acetate fractions in LPS-induced RAW 264.7 cells. These data suggest that OJE and its fraction possess pharmacological activity and might be useful for development of anti-inflammatory agents or dietary supplements.

The Effects of Sea Cucumber as an Anti-gastritis, Anti-gastric Ulcer, and Anti-Helicobater

Sea cucumber, , is used not only as an outstanding tonic food but also as a traditional medicine for the treatment of asthma, hypertension, rheumatism, anemia, and sinus congestion. The purpose of this study was to examine sea cucumber as an anti-gastritis and anti-gastric ulcer in HCl-ethanol-induced gastric and -infected animal models. Thirty 7-week-old SD rats and Mongolian gerbils were divided into normal (Nor, n

Anti-hyperglycemic effects and signaling mechanism of Perilla frutescens sprout extract

BACKGROUND/OBJECTIVES Perilla frutescens (L.) Britton var. (PF) sprout is a plant of the labiate family. We have previously reported the protective effects of PF sprout extract on cytokine-induced β-cell damage. However, the mechanism of action of the PF sprout extract in type 2 diabetes (T2DM) has not been investigated. The present study was designed to study the effects of PF sprout extract and signaling mechanisms in the T2DM mice model using C57BL/KsJ-db/db (db/db) mice. MATERIALS/METHODS Male db/db mice were orally administered PF sprout extract (100, 300, and 1,000 mg/kg of body weight) or rosiglitazone (RGZ, positive drug, 1 mg/kg of body weight) for 4 weeks. Signaling mechanisms were analyzed using liver tissues and HepG2 cells. RESULTS The PF sprout extract (300 and 1,000 mg/kg) significantly reduced the fasting blood glucose, serum insulin, triglyceride and total cholesterol levels in db/db mice. PF sprout extract also significantly improved glucose intolerance and insulin sensitivity, decreased hepatic gluconeogenic protein expression, and ameliorated histological alterations of the pancreas and liver. Levels of phosphorylated AMP-activated protein kinase (AMPK) protein expression also increased in the liver after treatment with the extract. In addition, an increase in the phosphorylation of AMPK and decrease in the phosphoenolpyruvate carboxykinase and glucose 6-phosphatase proteins in HepG2 cells were also observed. CONCLUSIONS Our results sugges that PF sprout displays beneficial effects in the prevention and treatment of type 2 diabetes via modulation of the AMPK pathway and inhibition of gluconeogenesis in the liver.

The medicinal mushroom Auricularia auricula-judae (Bull.) extract has antioxidant activity and promotes procollagen biosynthesis in HaCaT cells

Abstract In this study, Auricularia auricula-judae (Bull.) extract (AAE) had potent antioxidant activity in vitro and promoted the biosynthesis of procollagen, a precursor of collagen in HaCaT cells. In addition, the expression of HAS-3 (hyaluronic acid synthase), which is a moisturizing factor, was increased in HaCaT cells in response to AAE. Therefore, this work suggests that AAE has the potential to exhibit antioxidant activity and promote procollagen biosynthesis in HaCaT cells.

Perilla frutescens Sprout Extracts Protected Against Cytokine-induced Cell Damage of Pancreatic RINm5F Cells via NF-κB Pathway

Perilla frutescens (L.) Britton var. sprouts (PFS) is a plant of the labiatae family. The purpose of this work was to assess the preventive effects of PFS ethanolic extracts (PFSEs) on cytokine-induced β-cell damage. Cytokines, which are released by the infiltration of inflammatory cells around the pancreatic islets, are involved in the pathogenesis of type 1 diabetes mellitus. The combination of interleukin-1β (IL-1), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) induced formation of reactive oxygen species (ROS). Accumulation of intracellular ROS led to β-cell dysfunction and apoptosis. PFSEs possess antioxidant activity and thus lead to downregulation of ROS generation. Cytokines decrease cell viability, stimulate the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and induce the production of nitric oxide (NO). PFSEs prevented cytokine-induced cell viability in a dose-dependent manner. Incubation with PFSE resulted in significant reduction in cytokine-induced NO production that correlated with reduced levels of the iNOS and COX-2 protein expression. Furthermore, PFSE significantly decreased the activation of nuclear factor κB (NF-κB) by inhibition of IκBα phosphorylation in RINm5F cells. In summary, our results suggest that the protective effects of PFSE might serve to counteract cytokine-induced β-cell destruction. Findings indicate that consumption of Perilla frutescens (L.) Britton var. sprouts alleviates hyperglycemia-mediated oxidative stress and pro-inflammatory cytokine-induced β-cell damage and thus has beneficial anti-diabetic effects.