In-Chul Lee

Anti-inflammatory functions of purpurogallin in LPS-activated human endothelial cells

Enzymatic oxidation of commercially available pyrogallol was efficiently transformed to an oxidative product, purpurogallin. Purpurogallin plays an important role in inhibiting glutathione S-transferase, xanthine oxidase, catechol O-methyltransferase activities and is effective in the cell protection of several cell types. However, the anti-inflammatory functions of purpurogallin are not well studied. Here, we determined the effects of purpurogallin on lipopolysaccharide (LPS)-mediated proinflammatory responses. The results showed that purpurogallin inhibited LPS-mediated barrier hyper-permeability, monocyte adhesion and migration and such inhibitory effects were significantly correlated with the inhibitory functions of purpurogallin on LPS-mediated cell adhesion molecules (vascular cell adhesion molecules, intracellular cell adhesion molecule, E-selectin). Furthermore, LPS-mediated nuclear factor-κB (NF-κB) and tumor necrosis factor-α (TNF-α) releases from HUVECs were inhibited by purpurogallin. Given these results, purpurogallin showed its anti-inflammatory activities and could be a candidate as a therapeutic agent for various systemic inflammatory diseases. [BMB reports 2012; 45(3): 200-205].

Anti-inflammatory effects of kaempferol-3-O-sophoroside in human endothelial cells.

BackgroundKaempferol-3-O-sophoroside (KPOS) was isolated from the leaves of cultivated mountain ginseng. Kaempferol (KP) has antitumor, anti-oxidative, anti-allergic and antidiabetic activities but the barrier protective effects and underlying mechanism are not fully identified. In this study, we attempted to determine whether pretreatment with KPOS induced significant barrier protective activities in lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs).MethodsThe anti-inflammatory activities of KPOS were determined by measuring solute flux, neutrophil adhesion and migration and activation of pro-inflammatory proteins in LPS-activated HUVECs.ResultsWe found that KPOS inhibited LPS-induced barrier disruption, expression of cell adhesion molecules, neutrophil adhesion and transendothelial migration of neutrophils to HUVECs. Further studies revealed that KPOS suppressed the production of tumor necrosis factor-α (TNF-α) and activation of nuclear factor-κB (NF-κB) by LPS, and that anti-inflammatory activities of KPOS were better than those of KP.ConclusionCollectively, these results suggest that KPOS possesses barrier integrity activity, inhibitory activity on cell adhesion and migration to endothelial cells by blocking the activation of NF-κB expression and production of TNF-α, thereby endorsing its usefulness as therapy for vascular inflammatory diseases.

SOI high voltage integrated circuit technology for plasma display panel drivers

We have developed 150 V and 250 V high voltage integrated circuit technologies using high performance extended drain MOSFET (EDMOSFET) and dielectric isolation (DI) technology for data and scan driving LSIs of color AC plasma display panel systems for an application of HDTV. The EDMOSFETs have invariant channel length despite process variation because of a self-aligned structure. This results in smaller chip area for the developed driver LSIs than that of conventional driver LSIs using LDMOSFETs. The data driver LSI with maximum driving current of 50 mA and 60 output channels can be applied to PDP systems with a fast addressing time of 0.7 /spl mu/s. The scan driver LSI for large-size AC PDPs has a maximum driving current of 500 mA for both the source and the sink.

Antithrombotic activities of oroxylin A in vitro and in vivo

Here, the anticoagulant activities of oroxylin A (OroA), a major component of Scutellaria baicalensis Georgi, were examined by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT), and the activities of cell-based thrombin and activated factor X (FXa). Furthermore, the effects of OroA on the expressions of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were tested in tumor necrosis factor (TNF)-α activated human umbilical vein endothelial cells (HUVECs). Treatment with OroA resulted in prolonged aPTT and PT and inhibition of the activities of thrombin and FXa, and OroA inhibited production of thrombin and FXa in HUVECs. And OroA inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. In accordance with these anticoagulant activities, OroA elicited anticoagulant effects in mouse. In addition, treatment of OroA resulted in the inhibition of TNF-α-induced production of PAI-1, and treatment with OroA resulted in the significant reduction of the PAI-1 to t-PA ratio. Collectively, OroA possess antithrombotic activities and offer bases for development of a novel anticoagulant.

Anti-inflammatory effects of vicenin-2 and scolymoside on polyphosphate-mediated vascular inflammatory responses.

AbstractAim and objectiveRecent results indicate that polyphosphate (polyP) released by human endothelial cells can function as a pro-inflammatory mediator. Cyclopia subternata is a medicinal plant commonly used in traditional medicine to relieve pain in biological processes. This study was undertaken to investigate whether two structurally related active compounds found in C. subternata, namely vicenin-2 and scolymoside, can modulate polyP-mediated inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice.MethodsThe anti-inflammatory activities of vicenin-2 and scolymoside were determined by measuring permeability, leukocytes adhesion and migration, and activation of pro-inflammatory proteins in polyP-activated HUVECs and mice. In addition, the beneficial effects of vicenin-2 and scolymoside on survival rate in polyP-injected mice were determined.ResultsWe found that vicenin-2 and scolymoside inhibits polyP-mediated barrier disruption, the expressions of cell adhesion molecules, and leukocyte to HUVEC adhesion/migration. Interestingly, polyP-induced NF-κB activation and the productions of TNF-α and IL-6 were inhibited by vicenin-2 and scolymoside in HUVECs. These anti-inflammatory functions of vicenin-2 and scolymoside were confirmed in polyP-injected mice.ConclusionsThese results suggest that vicenin-2 and scolymoside have therapeutic potential for various systemic inflammatory diseases.

Anti-septic Effects of Pellitorine in HMGB1-Induced Inflammatory Responses In Vitro and In Vivo

High mobility group box 1 (HMGB1) acts as a late mediator of vascular inflammatory conditions. Pellitorine (PT), an active amide compound from Asarum sieboldii, is known to possess antibacterial and anticancer properties. In this study, we investigated the anti-septic effects of PT against pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) induced by HMGB1 and the associated signaling pathways. According to our findings, treatment with PT resulted in inhibited release of HMGB1, down-regulation of HMGB1-dependent inflammatory responses in HUVECs, and inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with PT resulted in reduced cecal ligation and puncture (CLP)-induced release of HMGB1 and sepsis-related mortality. PT suppressed the production of tumor necrosis factor-α and interleukin 6 and the activation of nuclear factor-κB and extracellular regulated kinases 1/2 by HMGB1. Collectively, these results indicate the potential of PT as a candidate therapeutic agent for treatment of various severe vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.

Antithrombotic activities of pellitorine in vitro and in vivo

Pellitorine (PLT), an active amide compound, is well known to possess insecticidal, antibacterial and anticancer properties. However, the anti-coagulant functions of PLT are not studied yet. Here, the anticoagulant activities of PLT were examined by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT), and the activities of cell-based thrombin and activated factor X (FXa). Furthermore, the effects of PLT on the expressions of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were tested in tumor necrosis factor (TNF)-α activated human umbilical vein endothelial cells (HUVECs). Treatment with PLT resulted in prolonged aPTT and PT and inhibition of the activities of thrombin and FXa, and PLT inhibited production of thrombin and FXa in HUVECs. And PLT inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. In accordance with these anticoagulant activities, PLT elicited anticoagulant effects in mouse. In addition, treatment with PLT resulted in the inhibition of TNF-α-induced production of PAI-1 and in the significant reduction of the PAI-1 to t-PA ratio. Collectively, PLT possesses antithrombotic activities and offers bases for development of a novel anticoagulant.

Electron paramagnetic resonance investigation of different plant organs after gamma irradiation

Total reactive oxygen species (ROS) signals in irradiated Arabidopsis plants were examined by electron paramagnetic resonance (EPR) analysis. At 10 kGy, the EPR signal intensity was highest in the root, whereas relatively low intensity levels were observed in the leaf and stem. The relative unit (r.u.) of control plants was 0.38 in the leaf, which was gradually increased to 0.51, 0.71, and 0.95 r.u. at 1, 5, and 10 kGy, respectively. In the stem, the intensity in all irradiated samples was lowest compared with that in other plant organs such as the leaf and root. The r.u. in the root sharply increased from 0.13 r.u. in control samples to 1.58 r.u. at 10 kGy, with 0.30–0.42 r.u. observed in 1–5 kGy irradiated samples. Stem and leaf extracts showed remarkably high levels of radical scavenging activity at 89.12 and 71.45%, respectively, compared with the very low level of activity in the root at 10.75%. These findings were in good agreement with the extraction yield of each plant organ, which was 20.0, 14.8, and 10.0% in the stem, leaf, and root, respectively. Order of EPR signal intensity and radical scavenging activity was as follows: EPR signal intensity: 1) leaf > root > stem at 1 and 5 kGy, 2) root > leaf > stem at 10 kGy; radical scavenging activity: stem > leaf > root. Results showed high or low levels of EPR signal intensity in different plant organs could be caused by the ROS removal power of extracts from different plant organs.

Inhibitory Effects of Rutin on the Endothelial Protein C Receptor Shedding In Vitro and In Vivo

Endothelial cell protein C receptor (EPCR) has important functions in regulation of coagulation and inflammation. EPCR shedding from the cell surface is mediated by tumor necrosis factor-α converting enzyme (TACE). Rutin is one of the major flavonoids from the buckwheat plant Fagopyrum tataricum. In this study, we investigated the effects of rutin on phorbol-12-myristate 13-acetate (PMA), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and on cecal ligation and puncture (CLP)-mediated EPCR shedding. We used a CLP model because this model more closely resembles human sepsis. Data showed rutin was a potent inhibitor of PMA, TNF-α, IL-1β, and CLP-induced EPCR shedding by suppression of TACE expression. Treatment with rutin resulted in a decrease of PMA-stimulated phosphorylation of p38, extracellular regulated kinases 1/2, and c-Jun N-terminal kinase. These results suggest the potential application of rutin for treatment of PMA and CLP-mediated EPCR shedding.

Sulforaphane Reduces HMGB1-Mediated Septic Responses and Improves Survival Rate in Septic Mice

Sulforaphane (SFN), a natural isothiocyanate present in cruciferous vegetables such as broccoli and cabbage, is effective in preventing carcinogenesis, diabetes, and inflammatory responses. Inhibition of high mobility group box 1 (HMGB1) and restoration of endothelial integrity is emerging as an attractive therapeutic strategy in the management of severe sepsis or septic shock. In this study, we examined the effects of SFN on HMGB1-mediated septic responses and survival rate in a mouse sepsis model. The anti-inflammatory activities of SFN were monitored based on its effects on lipopolysaccharide (LPS)- or cecal ligation and puncture (CLP)-mediated release of HMGB1. The antiseptic activities of SFN were determined by measuring permeability, leukocyte adhesion and migration, and the activation of pro-inflammatory proteins in HMGB1-activated human umbilical vein endothelial cells (HUVECs) and mice. SFN inhibited the release of HMGB1 and downregulated HMGB1-dependent inflammatory responses in human endothelial cells. SFN also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with SFN reduced CLP-induced release of HMGB1 and sepsis-related mortality and pulmonary injury in vivo. Our results indicate that SFN is a possible therapeutic agent that can be used to treat various severe vascular inflammatory diseases via the inhibition of the HMGB1 signaling pathway.