Hyejin Kang

Antitcoagulant and antiplatelet activities of scolymoside

Cyclopia subternata is a medicinal plant commonly used in traditional medicine to relieve pain. Here, the anticoagulant effects of scolymoside, an active compound in C. subternata, were examined by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT), and the activities of thrombin and activated factor X (FXa). The effects of scolymoside on plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) expression were evaluated in tumor necrosis factor (TNF)-α-activated human endothelial cells. Treatment with scolymoside resulted in prolonged aPTT and PT and the inhibition of thrombin and FXa activities and production. In addition, scolymoside inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. Scolymoside also elicited anticoagulant effects in mice, including a significant reduction in the PAI-1 to t-PA ratio. Collectively, these findings indicate that scolymoside possesses anticoagulant activities and could be developed as a novel anticoagulant. [BMB Reports 2015; 48(10): 577-582]

Anti-septic effects of dabrafenib on HMGB1-mediated inflammatory responses

A nucleosomal protein, high mobility group box 1 (HMGB1) is known to be a late mediator of sepsis. Dabrafenib is a B-Raf inhibitor and initially used for the treatment of metastatic melanoma therapy. Inhibition of HMGB1 and renewal of vascular integrity is appearing as an engaging therapeutic strategy in the administration of severe sepsis or septic shock. Here, we examined the effects of dabrafenib (DAB) on the modulation of HMGB1-mediated septic responses. DAB inhibited the release of HMGB1 and downregulated HMGB1-dependent inflammatory responses by enhancing the expressions of cell adhesion molecules (CAMs) in human endothelial cells. In addition, treatment with DAB inhibited the HMGB1 secretion by CLP and sepsis-related mortality and pulmonary injury. This study demonstrated that DAB could be alternative therapeutic options for sepsis or septic shock via the inhibition of the HMGB1 signaling pathway. [BMB Reports 2016; 49(4): 214-219]

Anti-inflammatory effects of vicenin-2 and scolymoside in vitro and in vivo

Aim and objectiveTwo structurally related flavonoids found in Cyclopia subternata, namely vicenin-2 and scolymoside, were examined for its effects on inflammatory responses by monitoring the effects of vicenin-2 and scolymoside on lipopolysaccharide (LPS)-mediated vascular inflammatory responses.MethodsThe anti-inflammatory activities of vicenin-2 and scolymoside were determined by measuring permeability, monocytes adhesion and migration, and activation of pro-inflammatory proteins in LPS-activated HUVECs and mice.ResultsWe found that post-treatment of each compound inhibited LPS-induced barrier disruption, expression of cell adhesion molecules (CAMs), and adhesion/transendothelial migration of human neutrophils to human endothelial cells. Each compound induced potent inhibition of phorbol-12-myristate 13-acetate (PMA) and LPS-induced endothelial cell protein C receptor (EPCR) shedding. It also suppressed LPS-induced hyperpermeability and leukocytes migration in vivo. Furthermore, each compound suppressed the production of tumor necrosis factor-α (TNF-α) or Interleukin (IL)-6 and the activation of nuclear factor-κB (NF-κB) or extracellular regulated kinases (ERK) 1/2 by LPS. Moreover, post-treatment with each compound resulted in reduced LPS-induced lethal endotoxemia.ConclusionVicenin-2 and scolymoside possess anti-inflammatory functions by inhibiting hyperpermeability, expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases.

Flavanones and Chromones from Salicornia herbacea Mitigate Septic Lethality via Restoration of Vascular Barrier Integrity.

Salicornia herbacea is an annual halophytic glasswort that has been employed as a culinary vegetable, salad, and traditional medicinal resource. Chemical investigation of the aerial parts of S. herbacea led to the isolation of two new (1, 2) and known (3) flavanones as well as a new nature-derived (4) and two known chromone derivatives (5, 6). These purified compounds were evaluated for their suppressive potentials against the release of high-mobility group box 1 protein (HMGB1), which has captured attention as a viable target for alleviating serious septic manifestations or septicemia. The phenolic compounds improved the survival rates of cecal ligation and puncture operation (CLP) in murine models, simulating severe septic shock and its related complications, to 40-60%. These results collectively validate that flavanone- and chromone-based secondary metabolites may serve as prospective prodrugs or food additives that may be commercialized for the control of septic complications and lethality.

Methylthiouracil, a new treatment option for sepsis

The screening of bioactive compound libraries can be an effective approach for repositioning FDA-approved drugs or discovering new treatments for human diseases. Inhibition of high mobility group box 1 (HMGB1) and restoration of endothelial integrity are emerging as an attractive therapeutic strategies in the management of severe sepsis or septic shock. Here, we examined the effects of methylthiouracil (MTU), used as antithyroid drug, by monitoring the effects on lipopolysaccharide (LPS)- or cecal ligation and puncture (CLP)-mediated release of HMGB1, and on the modulation of HMGB1-mediated inflammatory responses. The anti-inflammatory activities of MTU were determined by measuring permeability, leukocyte adhesion and migration, and the activation of pro-inflammatory proteins in HMGB1-activated HUVECs and mice. MTU inhibited the release of HMGB1 and downregulated HMGB1-dependent inflammatory responses in human endothelial cells. MTU also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with MTU reduced CLP-induced release of HMGB1 and sepsis-related mortality and pulmonary injury. Our results indicate that MTUs could be candidate therapeutic agents for various severe vascular inflammatory diseases via the inhibition of the HMGB1 signaling pathway.

Three diketopiperazines from marine-derived bacteria inhibit LPS-induced endothelial inflammatory responses

Diketopiperazine is a natural products found from bacteria, fungi, marine sponges, gorgonian and red algae. They are cyclic dipeptides possessing relatively simple and rigid structures with chiral nature and various side chains. Endothelial dysfunction is a key pathological feature of many inflammatory diseases, including sepsis. In the present study, three (1-3) of diketopiperazines were isolated from two strains of marine-derived bacteria. The compounds were investigated for their effects against lipopolysaccharide (LPS)-mediated endothelial inflammatory responses in vitro and in vivo. From 1 μM, 1-3 inhibited LPS-induced hyperpermeability, adhesion, and migration of leukocytes across a human endothelial cell monolayer and in mice in a dose-dependent manner suggesting that 1-3 may serve as potential scaffolds for the development of therapeutic agents to treat vascular inflammatory disorders.

Inhibitory effect of polyozellin on secretory group IIA phospholipase A2

The expression of secretory group IIA phospholipase A2 (sPLA2-IIA) is enhanced by development of inflammatory disorders. In this study, sPLA2-IIA expression was induced in the lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells and mice to evaluate the effect of polyozellin. Polyozellin, a major constituent of a Korea edible mushroom Polyozellus multiplex, has been known to exhibit the biological activities such as anti-oxidative and anti-inflammatory effects. Polyozellin remarkably suppressed the LPS-mediated protein expression and activity of sPLA2-IIA via inhibition of phosphorylation of cytosolic phospholipase A2 and extracellular signal-regulated kinase 1/2. These results demonstrated that polyozellin might play an important role in the modulation of sPLA2-IIA expression and activity in response to the inflammatory diseases.

Synthesis of non-fluorinated paraffinic water repellents and application properties on textile fabrics

The five non-fluorinated paraffinic water repellents having different lengths of alkyl groups were synthesized by emulsion polymerization. The number and weight average molecular weights were obtained at around 86,000-150,000 and 170,000-470,000, respectively. As the length of alkyl groups increased, the average molecular weight tended to decrease and the melting points gradually increased from 4.8 °C to 66.7 °C. The optimum length of alkyl group of paraffinic water repellents could be determined as hexadecyl and octadecyl and they showed the contact angle higher than 130 °. The critical surface tensions were obtained at 20-21 mN/m, there was no significant difference according to the length of alkyl groups between hexadecyl and docosyl groups.

Suppressive Effects of Pelargonidin on Endothelial Protein C Receptor Shedding via the Inhibition of TACE Activity and MAP Kinases.

Beyond its role in the activation of protein C, the endothelial cell protein C receptor (EPCR) plays an important role in the cytoprotective pathway. EPCR can be shed from the cell surface, which is mediated by tumor necrosis factor-[Formula: see text] converting enzyme (TACE). Pelargonidin is a well-known red pigment found in plants, and has been reported to have important biological activities that are potentially beneficial to human health. However, little is known about the effects of pelargonidin on EPCR shedding. We investigated this issue by monitoring the effects of pelargonidin on phorbol-12-myristate 13-acetate (PMA)-, tumor necrosis factor (TNF)-[Formula: see text]-, interleukin (IL)-1β-, and cecal ligation and puncture (CLP)-mediated EPCR shedding and by investigating the underlying mechanism of pelargonidin action. Data demonstrate that pelargonidin induced potent inhibition of PMA-, TNF-[Formula: see text]-, IL-1β-, and CLP-induced EPCR shedding by inhibiting the phosphorylation of mitogen-activated protein kinases (MAPKs) such as p38, janus kinase (JNK), and extracellular signal-regulated kinase (ERK) 1/2. Pelargonidin also inhibited the expression and activity of PMA-induced TACE in endothelial cells. These results demonstrate the potential of pelargonidin as an anti-EPCR shedding reagent against PMA- and CLP-mediated EPCR shedding.