Kyung-Sik Song

Decursin Inhibits Induction of Inflammatory Mediators by Blocking Nuclear Factor-κB Activation in Macrophages

In the course of screening inhibitors of matrix metalloproteinase (MMP)-9 induction in macrophages, we isolated decursin, a coumarin compound, from the roots of Angelicae gigas. As a marker for the screening and isolation, we tested expression of MMP-9 in RAW264.7 cells and THP-1 cells after treatment with bacterial lipopolysaccharide (LPS), the TLR-4 ligand. Decursin suppressed MMP-9 expression in cells stimulated by LPS in a dose-dependent manner at concentrations below 60 μM with no sign of cytotoxicity. The suppressive effect of decursin was observed not only in cells stimulated with ligands for TLR4, TLR2, TLR3, and TLR9 but also in cells stimulated with interleukin (IL)-1β, and tumor necrosis factor (TNF)-α, indicating that the molecular target of decursin is common signaling molecules induced by these stimulants. In addition to the suppression of MMP-9 expression, decursin blocked nitric oxide production and cytokine (IL-8, MCP-1, IL-1β, and TNF-α) secretion induced by LPS. To find out the molecular mechanism responsible for the suppressive effect of decursin, we analyzed signaling molecules involved in the TLR-mediated activation of MMP-9 and cytokines. Decursin blocked phosphorylation of IκB and nuclear translocation of NF-κB in THP-1 cells activated with LPS. Furthermore, expression of a luciferase reporter gene under the promoter containing NF-κB binding sites was blocked by decursin. These data indicate that decursin is a novel inhibitor of NF-κB activation in signaling induced by TLR ligands and cytokines.

Anti-inflammatory activity of flavonoids from Populus davidiana.

Anin vitro bioassay-guide revealed that the methanol (MeOH) extract of the stem bark ofPopulus davidiana showed considerable inhibitory activity against cyclooxygenase (COX-1, COX-2). Continuous phytochemical study of the MeOH extract of this plant led to the isolation of ten flavonoids; sakuranetin (1), rhamnocitrin (2), 7-O-methylaromadendrin (3), naringenin (4), eriodictyol (5), aromadendrin (6), kaempferol (7), neosakuranin (8), sakuranin (9) and sakurenetin-5,4′-di-β-D-glucopyranoside (10). Their structures were identified on the basis of their physicochemical and spectroscopic analyses. The isolated compounds,1–10, were tested for their inhibitory activities against COX-1 and COX-2. Compound7 was found to have potent inhibitory effect on COX-1 and a moderate effect on COX-2, meanwhile, compounds1–6 showed moderate inhibition against COX-1 only. Moreover, compounds5–8 exhibited suppressive effects on xanthine oxidase (XO). These results may explain, in part, the traditional uses ofP. davidiana in ethnomedicine.

Growth promotion of red pepper plug seedlings and the production of gibberellins by Bacillus cereus, Bacillus macroides and Bacillus pumilus.

The growth of red pepper plug seedlings was promoted by Bacillus cereus MJ-1, B. macroides CJ-29, and B. pumilus CJ-69 isolated from the rhizosphere. Gibberellins (GAs), a well-known plant growth-promoting hormone, were detected in the culture broth of their rhizobacteria. Among the GAs, the contents of GA1, GA3, GA4, and GA7, physiologically active GAs, were comparatively higher than those of others, suggesting that the growth promoting effect was originated from the GAs. This is the first report on the production of GA5, GA8, GA34, GA44, and GA53 by bacteria.

Decursin inhibits induction of inflammatory mediators by blocking NF-κB activation in macrophages

In the course of screening inhibitors of matrix metalloproteinase (MMP)-9 induction in macrophages, we isolated decursin, a coumarin compound, from the roots of Angelicae gigas. As a marker for the screening and isolation, we tested expression of MMP-9 in RAW264.7 cells and THP-1 cells after treatment with bacterial lipopolysaccharide (LPS), the TLR-4 ligand. Decursin suppressed MMP-9 expression in cells stimulated by LPS in a dose-dependent manner at concentrations below 60 μM with no sign of cytotoxicity. The suppressive effect of decursin was observed not only in cells stimulated with ligands for TLR4, TLR2, TLR3, and TLR9 but also in cells stimulated with interleukin (IL)-1β, and tumor necrosis factor (TNF)-α, indicating that the molecular target of decursin is common signaling molecules induced by these stimulants. In addition to the suppression of MMP-9 expression, decursin blocked nitric oxide production and cytokine (IL-8, MCP-1, IL-1β, and TNF-α) secretion induced by LPS. To find out the molecular mechanism responsible for the suppressive effect of decursin, we analyzed signaling molecules involved in the TLR-mediated activation of MMP-9 and cytokines. Decursin blocked phosphorylation of IκB and nuclear translocation of NF-κB in THP-1 cells activated with LPS. Furthermore, expression of a luciferase reporter gene under the promoter containing NF-κB binding sites was blocked by decursin. These data indicate that decursin is a novel inhibitor of NF-κB activation in signaling induced by TLR ligands and cytokines.

β-secretase (BACE1) inhibitors from Pomegranate (Punica granatum) husk

In the course of screening for anti-dementia agents from natural products, two β-secretase (BACE1) inhibitors were isolated from the husk of pomegranate(Punica granatum) by activity-guided purification. They were identified as ellagic acid and punicalagin with IC50 values of 3.9 x10-6 and 4.1x10-7 M andKi values of 2.4x10-5 and 5.9x10-7 M, respectively. The compounds were non-competitive inhibitors with a substrate in the Dixon plot. Ellagic acid and punicalagin were less inhibitory to α-secretase (TACE) and other serine proteases such as chymotrypsin, trypsin, and elastase, thus indicating that they were relatively specific inhibitors of BACE1.

Comparison of remineralization effect of three topical fluoride regimens on enamel initial carious lesions

OBJECTIVES Some studies have been conducted to evaluate the effect of different topical fluoride regimens on the remineralization of initial carious lesions. This study was conducted to compare the effects of 3 topical fluoride treatments on the surface microhardness, fluoride uptake, and fluorescence lesion area in enamel. METHODS Forty-eight bovine teeth were demineralized and subjected to one of the following treatments: (1) no treatment (control), (2) iontophoresis using 2% sodium fluoride solution, (3) 1.23% acidulated phosphate fluoride gel application, and (4) 5% sodium fluoride varnish application. Six persons continuously wore a mandibular removable appliance mounted with eight treated bovine teeth orally for 4 weeks, except while eating, sleeping, and brushing. Microhardness of enamel surfaces was measured using a digital microhardness tester. The fluoride concentration was analyzed using a fluoride electrode, and the fluorescence lesion area was calculated by confocal laser scanning microscopy. RESULTS No significant differences in the microhardness were observed in response to the 3 fluoride regimens. The highest level of fluoride was observed in the APF gel group. APF gel group also showed significantly reduced fluorescence lesion areas compared to those of the control group. CONCLUSIONS The fluoride regimens showed no difference in surface microhardness; although APF gel showed the best effects in terms of fluoride uptake and decrease in the fluorescence lesion area, its effects were not significantly different from those of fluoride varnish.

An antioxidant hispidin from the mycelial cultures of Phellinus linteus.

In the course of screening for reactive oxygen species scavengers from natural products, an antioxidant was isolated from the mycelial culture broth ofPhellinus linteus and identified as hispidin. The hispidin content was reached its maximum level at 12 days after onset of inoculation. About 2.5 mg/mL of hispidin was produced byP. linteus in a yeast-malt medium (pH 5.8, 25°C). Hispidin inhibited 22.6 and 56.8% of the super oxide anion radical, 79.4 and 95.3% of the hydroxyl radical, and 28.1 and 85.5% of the DPPH radical at 0.1 and 1.0 mM, respectively. The positive control oc-tocopherol scavenged 25.6 and 60.3%, 74.6 and 96.3%, and 32.7 and 77.5% of each radical, respectively, at the same concentrations. However, hispidin showed no significant activity on the hydrogen peroxide radical.

Isoliquiritigenin isolated from Glycyrrhiza uralensis protects neuronal cells against glutamate-induced mitochondrial dysfunction

Glutamate-mediated excitotoxicity, which is associated with reactive oxygen species (ROS), is hypothesized to be a major contributor to pathological cell death in the mammalian central nervous system, and to be involved in many acute and chronic brain diseases. Here, we showed that isoliquiritigenin (ISL) isolated from Glycyrrhiza uralensis (Gu), one of the most frequently prescribed oriental herbal medicines, protected HT22 hippocampal neuronal cells from glutamate-induced oxidative stress. In addition, we clarified the molecular mechanisms by which it protects against glutamate-induced neuronal cell death. ISL reversed glutamate-induced ROS production and mitochondrial depolarization, as well as glutamate-induced changes in expression of the apoptotic regulators Bcl-2 and Bax. Pretreatment of HT22 cells with ISL suppresses the release of apoptosis-inducing factor from mitochondria into the cytosol. Taken together, our results suggest that ISL may protect against mitochondrial dysfunction by limiting glutamate-induced oxidative stress. In conclusion, our results demonstrated that ISL isolated from Gu has protective effects against glutamate-induced mitochondrial damage and hippocampal neuronal cell death. We expect ISL to be useful in the development of drugs to prevent or treat neurodegenerative diseases.

Dental caries and salivary immunoglobulin A in Down syndrome children

Objectives:  This study investigated the relationship between dental caries and the salivary Streptococcus mutans specific antibodies in Down syndrome children.

Anti-inflammatory effects of oleanolic acid on LPS-induced inflammation in vitro and in vivo.

Oleanolic acid (OA) is a triterpenoid known for its anti-inflammatory and anti-cancer properties; however, the anti-inflammatory effects of OA on lipopolysaccharide (LPS)-mediated pro-inflammatory responses have not been studied. Here, we first investigated the possible anti-inflammatory effects of OA against pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) induced by LPS and the associated signaling pathways. We found that OA inhibited LPS-induced barrier disruption, expression of cell adhesion molecules (CAMs), and adhesion/transendothelial migration of monocytes to HUVECs. OA also suppressed acetic acid-induced hyperpermeability and carboxymethylcellulose-induced leukocyte migration in vivo. Further studies revealed that OA suppressed the production of tumor necrosis factor-α and activation of nuclear factor-κB by LPS. Collectively, these results suggest that OA has anti-inflammatory effects by inhibiting hyperpermeability, the expression of CAMs, and the adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapeutic agent for vascular inflammatory diseases.