Effect of β-Glucan Originated from Aureobasidium pullulans on Asthma Induced by Ovalbumin in Mouse

구세광,노성수,Joo Wan Kim,Hyung Rae Cho,Ki Young Kim,민유홍,박종현,김재수,박지하,서부일 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.6

The objective of this study is to detect the effect of beta-glucan derived from Aureobasidium pullulans SM-2001, a UV induced mutant of A. pullulans on the ovalbumin (OVA) induced allergic asthma. The test articles were orally administered to OVA-inducing asthmatic mice 4 days after sensitization for 13 days at 31.25, 62.5 or 125 mg/kg levels. Three days after the OVA sensitization, ten mice were selected per group based on body weight and were sacrificed three days after the OVA aerosol challenge. The changes on the body weight, lung weight, total leukocytes in peripheral blood and total cells in bronchoalveolar lavage fluid (BALF) were observed with changes on the lung histopathology and histomorphometry. The results were compared with dexamethasone (DEXA) 3 mg/kg intraperitoneally treated mice. The results showed increases of body weight after the OVA aerosol challenge, lung weight, total leukocytes and eosinophils in peripheral blood, total cell numbers, neutrophil and eosinophils in BALF were detected in the OVA control compared to sham control (non-OVA). However, these changes from asthmatic responses were significantly or dose-dependently decreased in the beta-glucan-dosing groups compared to those of the OVA control. Therefore, it is concluded that beta-glucan has favorable effects on asthmatic response induced by OVA. It was found that beta-glucan 125 mg/kg showed similar or slightly lower efficacy compared with DEXA 3 mg/kg.

S. pneumoniae 호흡기감염 마우스에서 Ciprofloxacin의 항균력에 대한 조직학적 연구

구세광,이형식,김종대,최해윤,이재현 慶山大學校 基礎科學硏究所 2002 基礎科學 Vol.6 No.1

Sterptococcus pneumoniae ATCC 6303을 이용한 국소 호흡기 감염 마우스 모델에서 Ciprofloxacin (CPFX)의 in vivo 항균력을 조직학적으로 평가하기 위하여 생균수와 폐의 조직·병리학적 변화를 관찰하였던 결과, 다음과 같은 결과를 얻었다. 1) 생균수는 CPFX 투여군에서 Control 군에 비해 유의성 있게 감소되었으며, 2) Control 군에서는 현저한 폐내 염증세포의 침윤, 출혈 및 폐포 벽의 비후가 조직학적으로 관찰되었으나, 이러한 조직학적 소견들은 CPFX 투여군에서 Control 군에 비해 현저히 있게 감소되었고, 3) LSA (luminal surface of alveoli %)는 Control 군에서 Sham 군에 비해 현저히 감소된 반면, CPFX 투여군에서 Control 군에 비해 유의성 있게 증가되었다. 이상에서 본 실험의 결과, CPFX의 Sterptococcus pneumoniae에 대한 항균력이 조직학적으로 관찰되었다. In order to evaluate the in vivo effect of ciprofloxacin (CPFX), the viable bacterial number and histopathological changes were monitored after experimental respiratory infection with Sterptococcus pneumoniae ATCC 6303. In CPFX, the viable bacterial numbers were significantly and dose-dependently decreased compared to that of Control group. In Control group, severe infiltration of inflammatory cells, hemorrhage and hypertrophy of alveolar linings were demonstrated at microscopical levels. However, these abnormal histopathological changes were significantly and dose-dependently decreased compared to that of Control group in CPFX group. And also in CPFX group, the LSA (luminal surface of alveoli %) were significantly and dose-dependently increased compared to that of Control group. According to these results, it is considered as the in vivo antibacterial activity of CPFX was histologically showed against Sterptococcus pneumoniae ATCC 6303 infection of respiratory tract in this study.

Effect of Gongjindan, a Polyherbal Formula on the Pharmacokinetics Profiles of Sorafenib in Male SD Rats (1) - Single Oral Combination Treatment of Sorafenib 50mg/kg with Gongjindan 100mg/kg within 5min -

구세광,이영준,Kim, SeungMo,Lee, Chang Hyeong,Park, Soo Jin,Kang, Su Jin,Song, Chang Hyun,Han, Chang Hyun,Ku, Sae Kwang,Lee, Young Joon 대한예방한의학회 2014 대한예방한의학회지 Vol.18 No.2

Objective : The co-administration effects of Gongjindan (GJD) on the pharmacokinetics (PK) of sorafenib were observed as a process of the comprehensive and integrative medicine. Methods : After sorafenib treatment, GJD was administered within 5 min. The plasma were collected at 30min before administration, 30min, 1, 2, 3, 4, 6, 8 and 24hrs after end of GJD treatment, and plasma concentrations of sorafenib were analyzed using LC-MS/MS methods. PK parameters of sorafenib ($T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with sorafenib single administered rats. Results : The absorption of sorafenib were significantly increased at 30min, 1, 6 and 6hrs after co-administration with GJD as compared with sorafenib single treated rats. Accordingly, the $AUC_{0-t}$ (47.20%) of sorafenib was significantly increased but $t_{1/2}$ (-30.63%) and $MRT_{inf}$ (-34.11%) in co-administered rats were non-significantly decreased. These findings are considered as direct evidences that GJD increased the oral bioavailability of sorafenib through increase of the absorption, when they co-administered within 5min. Conclusion : Based on the results, co-administration of GJD increased the oral bioavailability of sorafenib through increase of the gastrointestinal absorption. It is considered that the more detail pharmacokinetic studies should be tested to conclude the effects of GJD on the pharmacokinetics of sorafenib, when they were co-administered, like the effects after co-administration with reasonable intervals considering the $T_{max}$ of sorafenib (about 3.5hr-intervals) and after repeated co-administrations.Hence, concomitant uses of GJD with sorafenib may require close monitoring for potential drug interactions.

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 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.

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.

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.

Hepatoprotective and Nephroprotective Effects of Allium victorialis Leaf Extracts on the High Fat Diet Supplied Mice

구세광,김주완 한국임상수의학회 2010 한국임상수의학회지 Vol.27 No.3

The hepatoprotective and nephroprotective effects of Allium victorialis (AV) methanol extracts were investigated on high fat diet (HFD) supplied mice. Treatment of AV extracts (62.5, 125, 250 mg/kg) once a day for 12 weeks markedly decreased the liver steatohepatitis and kidney damages. AV extracts were inhibited the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN) and creatinine elevations and reduced the histopathological changes of livers induced by HFD supply. In addition, AV extracts strengthened the antioxidative defense system with an increased activity of superoxide dismutase (SOD), glutathione (GSH), catalase and reduced malondialdehyde (MDA) levels. The 125 mg/kg of AV extract showed similar favorable effects as compared with silymarin 100 mg/kg. It is suggested that AV methanol extract administration is beneficial to the improvement of the alleviation of liver and kidney damages in HFD supplement.

Allium victorialis Leaf Extract Prevents High Fat Diet Induced Obesity in Mice

구세광,정인권,전우현,김주완 한국임상수의학회 2011 한국임상수의학회지 Vol.28 No.3

The antiobese effects of Allium victorialis (AV) leaf methanol extract were evaluated in a high fat diet (HFD) supplied mice. The changes on the body weight, food consumption, leptin and adiponectin levels as well as the periovarian fat weights and histopathology of adipocytes were examined. The effects were compared with those of a group given 250 mg/kg of metformin. After 91 days of a continuous HFD supply, the mice were significantly showed obesity. However, the obesity induced by the HFD was inhibited by the AV extract treatment at the three different doses (62.5, 125 and 250 mg/kg) respectively. The results suggest that the AV methanol extract is beneficial for improving the diet-induced obesity in humans.