Inhibitory Effects of Purpurogallin on the Endothelial Protein C Receptor Shedding in vitro and in vivo

구세광,이인철,배종섭 한국응용생명화학회 2013 Applied Biological Chemistry (Appl Biol Chem) Vol.56 No.5

Endothelial cell protein C receptor (EPCR) plays important roles in the regulation of blood coagulation and inflammation. Activity of EPCR is markedly changed by ectodomain cleavage and released as soluble protein (sEPCR). EPCR can be shed from the cell surface, and this is mediated by tumor necrosis factor-α converting enzyme (TACE). Purpurogallin (PPG) plays an important role in inhibiting glutathione Stransferase and xanthine oxidase as well as effective in the cell protection of several cell types. Here, we investigated the effects of PPG 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 and underlying mechanisms. Human umbilical vein endothelial cells pretreated with PPG (0, 5, 10, 20 or 50 μg/mL) for 6 h and exposed to PMA (1 μM) for 1 h, and CLP-operated mice were administrated with PPG. Data showed that treatment with PPG resulted in potent inhibition of PMA, TNF-α, IL-1β, and CLP-induced EPCR shedding by suppression of TACE expression. In addition, PPG reduced PMA-stimulated phosphorylation of p38, extracellular regulated kinases 1/2, and c-Jun N-terminal kinase. These results suggest the potential for use of PPG as an anti-sEPCR shedding reagent against PMA and CLP-mediated EPCR shedding.

Inhibitory effect of polyozellin on secretory group IIA phospholipase A2

구세광,양은주,Hyejin Kang,정병진,배종섭 대한약학회 2016 Archives of Pharmacal Research Vol.39 No.2

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.

흑효모유래 $\beta$-glucan의 패혈증 치료효과 및 항돌연변이 활성 평가

구세광,Ku, Sae-Kwang Korean Institute of Oriental Medicine 2009 한국한의학연구원논문집 Vol.15 No.3

Anti-mutagenic and anti-septic effects of $\beta$-1,3/1,6-glucan from Aureobasidium pullulans SM-2001 were evaluated on the on the cyclophosphamide (CPA)-cecal ligation puncture (CLP) and CPA-treated mice. To induce immunosuppression and mutagenicity, 150 and 110 mg/kg of CPA were single intraperitoneally injected at 3 or 1 day before CLP or initial $\beta$-glucan administration. In CLP animals, the cecum was mobilized and ligated below the ileocecal valve, punctured through both surfaces twice with a 22-gauge needle. 125 mg/kg of $\beta$-glucan were dissolved in saline and subcutaneously or orally administered in a volume of 10 ml/kg (of body weight), 4 times, 12 hrs intervals from 6 hrs after CLP or 1 day after second dose of CPA. After treatment of $\beta$-glucan, the mortalities were observed in CPA-CLP model, and the appearance of a micronucleus is used as an index for genotoxic potential in CPA model. As results of CPA-CLP sepsis, all animals (9/9, 100%) in CPA-CLP control were dead within 2 days after CLP. In addition, increase of the number of bone marrow MNPCEs indicated mutagenicity were also observed by treatment of CPA. However, $\beta$-glucan treatment effectively inhibited the mortalities in CPA-CLP, and it also reduced the CPA treatment-related mutagenicity, respectively. These results indicated that $\beta$-glucan has effective anti-septic and anti-mutagenic effects and can be used as an agents for treating sepsis and mutagenicity related to high-dose chemotherapy or radiotherapy. However, further studies should be conducted to observe more detail action mechanisms of it's anti-septic and anti-mutagenic effects.

닭 태자의 십이지장에 대한 조직학적 및 면역조직화학적 연구

구세광,박기대,이재현,이형식,Ku, Sae-kwang,Park, Ki-dae,Lee, Jae-hyun,Lee, Hyeung-sik 대한수의학회 1998 大韓獸醫學會誌 Vol.38 No.4

With histological changes, ontogeny and relative frequencies of bovine Sp-1/chromogranin(bCG)-, serotonin-, gastrin-, cholecystokinin-8(CCK-8)-, somatostatin-, S-100 protein-, polypeptide YY(PYY)- and glucagon-immunoreactive cells were investigated in the duodenum of the chicken embryos from 10 days of incubation to hatching. Histologically, pseudostraitified columnar epithelium were observed from 10 days of incubation to 14 days of incubation, thereafter these epithelium were differentiated to simple columnar epithelium. $Liberk{\ddot{u}}hn$ glands were observed from 18 days of incubation and goblet cells were detected from hatching. In the duodenum, bCG-immunoreactive cells were detected from 14 days of incubation and increased to 18 days of incubation, thereafter decreased with ages. Serotonin-immunorecative cells were detected from 14 days of incubation and increased with ages. Somatostatin-immunoreactive cells were detected from 14 days of incubation and CCK-immunoreactive cells were detected from 19 days of incubation. No gastrin-, S-100 protein-, PYY-, glucagon-immunoreactive cells were detected in this study.

A Histochemical Study of Argyrophil Cells in the Gastrointestinal Tract of Balb/c-nu/nu Mouse-Frequency And Distribution

구세광,이재현,이형식 한국실험동물학회 2005 Laboratory Animal Research Vol.21 No.1

Antithrombotic activities of oroxylin A in vitro and in vivo

구세광,이인철,배종섭 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.5

Here, the anticoagulant activities of oroxylin A(OroA), a major component of Scutellaria baicalensisGeorgi, were examined by monitoring activated partialthromboplastin time (aPTT), prothrombin time (PT), andthe activities of cell-based thrombin and activated factor X(FXa). Furthermore, the effects of OroA on the expressionsof plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were tested in tumornecrosis factor (TNF)-a activated human umbilical veinendothelial cells (HUVECs). Treatment with OroA resultedin prolonged aPTT and PT and inhibition of the activitiesof thrombin and FXa, and OroA inhibited production ofthrombin and FXa in HUVECs. And OroA inhibitedthrombin-catalyzed fibrin polymerization and plateletaggregation. In accordance with these anticoagulantactivities, OroA elicited anticoagulant effects in mouse. Inaddition, treatment of OroA resulted in the inhibition ofTNF-a-induced production of PAI-1, and treatment withOroA resulted in the significant reduction of the PAI-1 tot-PA ratio. Collectively, OroA possess antithromboticactivities and offer bases for development of a novelanticoagulant.

췌관을 결찰한 닭 췌장 외분비부의 형태학적 변화

구세광,이재현,이형식,Ku, Sae-kwang,Lee, Jae-hyun,Lee, Hyeung-sik 대한수의학회 1997 大韓獸醫學會誌 Vol.37 No.2

To investigate morphological changes in the exocrine pancreas of chicken after pancreatic duct ligation, experimental animals were subdivided to control, 12 hours, 1 day, 2 days, 4 days, 7 days and 10 days groupes and all of three pancreatic ducts of chicken were ligated by surgical procedure and then the morphological changes were observed. In pancreatic ducts, once for a while the ducts were dilated on 12 hours after pancreatic duct ligation and then they were obstructed because of proliferated epithelial cells and connective tissues in pancreatic duct. Marginal dissociation of acini was detected in 12 hours after pancreatic duct ligation and then dissociation of acini was increased with time and finally in 4 days after pancreatic duct ligation the acini showed completely dissociation except periductular regions and around pancreatic islets. Most of dissociated acini cells showed marginal condensation of nuclear chromatin and atropy of cytoplasm, namely, apoptotic features were detected in dissociated acinar cells. Interacinar spaces of dissociated acinar regions were dilated and fulfilled with increased connective tissue and in 4 days after pancreatic duct ligation, deposition of lymphocytes and hemocytes was occurred.

Antithrombotic activities of aspalathin and nothofagin via inhibiting platelet aggregation and FIIa/Fxa

구세광,이원화,광민,배종섭 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.6

Aspalathin (Asp) and nothofagin (Not) are twomajor active dihydrochalcones found in green rooibos tea(Aspalathus linearis; family, Fabaceae; tribe, Crotalarieae),which have been reported for their anti-oxidant activity. Here, the anticoagulant activities of Asp and Not wereexamined by monitoring activated partial thromboplastintime (aPTT), prothrombin time (PT), and the activities ofthrombin (Factor IIa, FIIa) and activated factor X (FXa). And, the effects of Asp and Not on expression of plasminogenactivator inhibitor type 1 (PAI-1) and tissue-typeplasminogen activator (t-PA) were evaluated in tumornecrosis factor (TNF)-a activated human umbilical veinendothelial cells (HUVECs). Treatment with Asp and Notresulted in prolonged aPTT and PT and inhibition of theactivities of thrombin and FXa, as well as inhibited productionof thrombin and FXa in HUVECs. In addition, Aspand Not inhibited thrombin-catalyzed fibrin polymerizationand platelet aggregation. Asp and Not also elicited anticoagulanteffects in mice. In addition, treatment with Aspand Not resulted in significant reduction of the PAI-1 tot-PA ratio. Collectively, Asp and Not possesses antithromboticactivities and offers a basis for development ofa novel anticoagulant.

청둥오리 위 내분비세포에 대한 면역조직화학적 연구

구세광,이형식,이재현,Ku, Sae-kwang,Lee, Hyeung-sik,Lee, Jae-hyun 대한수의학회 1998 大韓獸醫學會誌 Vol.38 No.3

The relative frequency and distribution of bovine chromogranin(BCG)-, serotonin-, somatostatin(SOM)-, and S-100 protein-immunoreactive cells in the proventriculus, gizzard and proventriculus-gizzard junction(P-G junction) of the duck(Anas platyrhynchos platyrhyncos, Linne) were studied using immunohistochemical methods. BCG-, and SOM-immunoreactive cells were detected in all ages of this study in the proventriculus and the gizzard, and BCG-immunoreactive cells were also detected in the P-G junction. SOM-immunoreactive cells were detected rarely on occasions only in 1 week, 2 weeks, 3 weeks and 9 weeks after hatching. But no S-100 protein-immunoreactive cells were detected in this study.

The anti-climacterium effects of red clover dry extracts combined with pomegranate concentration powder in ovariectomized rats

구세광,이영준,Kim, Kyung Hu,Kang, Su Jin,Choi, Beom Rak,Kim, Seung Hee,Yi, Hae Yeon,Kim, Dong Chul,Choi, Seong Hun,Han, Chang Hyun,Park, Soo Jin,Song, Chang Hyun,Ku, Sae Kwang,Lee, Young Joon 대한예방한의학회 2014 대한예방한의학회지 Vol.18 No.2

Objective : In this study, the addition of dried pomegranate concentrate powder (PCP) was affected the anti-climacterium activity of red clover dry extracts (RC) in ovariectomized (OVX) rats. Materials and methods : After bilateral OVX surgery, RC 40 mg/kg, PCP 20 mg/kg and RC:PCP 2:1 mixture (g/g) 120, 60 and 30 mg/kg (of body weight) were orally administered, once a day for 84 days, and then the changes on the serum estradiol levels, abdominal fat pad and uterus weights were observed for estrogenic effects. In addition, liver weights, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were also evaluated for hepatoprotective effects, and serum total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL) and triglyceride (TG) levels were monitored for hypolipidemic effects. Results : As a result of OVX, the estrogen-deficient climacterium symptoms, increments of abdominal fat pad weights, serum AST, ALT, TC, LDL and TG levels with decrease of uterus and liver weights, serum estradiol levels, were demonstrated. However, these estrogen-deficient climacterium symptoms induced by bilateral OVX in rats were significantly inhibited by continuous oral treatment of RC 40 mg/kg, PCP 20 mg/kg and RC:PCP 2:1 mixture (g/g) 120, 60 and 30 mg/kg, respectively. Conclusion : The results suggested that RC:PCP 2:1 mixtures synergistically increased the anti-climacterium effects of RC in OVX rats. It, therefore, is expected that RC:PCP 2:1 mixture will be promising as a new potent protective agents for relieving the climacterium symptoms.