11:10-12:00, Rm 103

Chemical biology and drug discoveryD-17-01Schisandrin prevent damage of murine mesangial cells via blockingROS signaling in high glucoseSeung-Il Jeong¹, Sang-Jun Kim¹, Tae-Ho Kwon¹, Kang-Yeol Yu¹, Seon-Young Kim¹ , *Jeonju Biomaterials Institute, KoreaHigh glucose (HG) is the underlying factor contributing to long term complication ofdiabetes mellitus. Reactive oxygen species (ROS) have been postulated as a unifyingmechanism for HG-induced complications. In this study we report the inhibitory effect ofschisandrin (Sch), an active ingredient of Fuctus shisandrea, on hyperglycemia inducedmurine mesangial cells (MMCs) damage. The molecular mechanisms of Sch responsiblefor inhibition of HG-mediated proliferation of MMCs were also examined. Sch treatmentsignificantly attenuated HG-induced proliferation of MMCs in a dose dependent manner(IC50; 100 µM). The intracellular reactive oxygen species (ROS) level was remarkablyreduced by Sch as well as levels of phospho-Erk 1/2 and Akt acitvation. Theaccumulation of extracellular matrix proteins, which are collagen IV and fibronectin, werealso down regulated by Sch treatment. Taken together, our demonstration of the ability ofSch to inhibit high glucose induced MMCs damage has clinical implications in treatmentof diabetic nephropathy.D-17-04Anti-lipase and lipolytic activities of extracts isolated from naturalproductsChanghyun Roh, Min-Kyoung Park, Hee-June Shin, Uhee Jung and Sung-Kee JoRadiation Research Division for Biotechnology, Advanced Radiation Technology Institute (ARTI),Korea Atomic Energy Research Institute (KAERI), KoreaObesity is a chronic metabolic disorder caused by an imbalance between energy intakeand expenditure. It has become a major obstacle of improving human health and lifequality due to the known risk factors for many chronic diseases. In this study, wescreened crude anti-obesity drugs from four-hundred natural sources on porcinepancreatic lipase in vitro activity. Among 400 natural sources examined, forty fourextracts from natural sources significantly inhibited in vitro activity against PPL bymeasuring the hydrolysis of p-nitrophenyl butyrate as a substrate to p-nitrophenol at 405nm. Furthermore, forty four natural sources were investigated to their lipid inhibition by OilRed O staining in 3T3-L1 cells. Among the forty four natural extracts examined, the fourpromising natural sources (Rubi Fructus, Corni Fructus, Salicis Radicis Cortex, andGeranium nepalense) were found to inhibit fat droplet formation triglyceride accumulationin 3T3-L1 adipocytes, suggesting anti-obesity activity. Interestingly, four natural sourcesshowed remarkable antioxidant activity in free radical 1,1-diphenyl-2-picrylhydrazyl(DPPH) scavenging and superoxide radical scavenging. This work was supported bygrant no. 2007-2000091 from Nuclear R&D Program of MEST.D-17-02A novel class of adamantyl derivatives as a potent MDR reversal agentsby inhibiting P-glycoproteinKyeong Lee, Ravi NaikCollege of Pharmacy, Dongguk University-Seoul, Seoul 100-715, KoreaMultidrug Resistance is a type of resistance of tumor cells to various kinds ofchemotherapeutic drugs which are structurally unrelated and also one of the majorimpediment to the successful chemotherapeutic treatment of cancer. There are 49 ATPbindingcassette (ABC) transporter genes present in the human genome. Among theseABC proteins, over expression of P-glycoprotein(P-gp),encoded by MDR1 gene is one ofthe major factor contributing to Multidrug Resistance which inturn leads to barrier tosuccessful chemotherapeutic agents. Thus the availability of safe and potent MultidrugResistance Reversal gents would be beneficial for clinical use, ultimately leading to thebenefit of human. Many modulators act by binding to membrane transport protein (P-gp)and inhibiting their drug effluxing capacity and some by inhibition of expression of MDR1gene itself. Thus in an attempt to find more potent MDR reversal agent, we synthesized anovel class of adamantyl derivatives which are 10 fold more efficient than verapamil(present clinical reversal agent) without considerable intrinsic cytotoxicity.D-17-05Flavonoid isolated from Carduus crispus controls spermatogenesis ontesticular germ cellSung-Kwang Yoo, Dong-Hyun Suh and Si-Kwan KimDepartment of Life Science, Konkuk University, Chungju-city, Chungbuk Pref. 380-701, KoreaAs with many flavonoids, apigenin has potential to reduce the risk of cancer since it hasanti-tumor activity. Apigenin also could potentially be useful in allergy conditions since itcan have anti-inflammatory properties. However, no report has been elucidated it’sspermatogenesis effect. Carduus crispus was extracted with 100% methanol three timesin reflux system. Then active fraction was obtained by ethyl acetate partition and silica gelcolumn chromatography with the solvent system of chloroform : ethyl acetate. Apigeninwas isolated from active fraction by recrystallization and high performance liquidchromatography. Apigenin had been used to explain spermatogenesis effect in ourexperiments. Effect of Nectin-2, Prx-3 and inhibin-αin spermatocyte GC-2pd(ts) cellshowed change by stimulation with 200 μM hydrogen peroxide. Interestingly, they wereconsiderably regulated by apigenin. Effect of apigenin in leydig TM3 cell and sertoli TM4cell were that the expreessions of nectin-2 and Prx-3 were completely attenuated byhydrogen peroxide. Apigenin dose-dependently ameliorated of nectin-2 and Prx-3. Theseresults show that apigenin leads us to expect the further development of drugs relationspermatogenesis.D-17-03Tangeretin, a citrus flavonoid, inhibits PGDF-BB-induced proliferationand migration of arotic smooth muscle cells by blocking AKT activationJuhee Seo, Suhyun Lee, Jeong-Hyung LeeDepartment of Biochemistry, College of Natural Sciences, Kangwon National University,Chuncheon, Gangwon-Do 200-701, KoreaTangeretin, a natural polymethoxylated flavone concentrated in the peel of citrus fruits, isknown to have anti-proliferative, anti-invasive, anti-metastatic, and antioxidant activities.However, the effect of tangeretin on vascular smooth muscle cells (VSMCs) is unknown.This study was examined the effect of tangeretin on platelet-derived growth factor(PDGF)-BB-induced proliferation and migration of rat aortic smooth muscle cells(RASMCs), and its underlying mechanisms. Tangeretin significantly inhibited theproliferation, DNA synthesis, and migration of PDGF-BB-stimulated RASMCs. Treatmentwith tangeretin induced cell-cycle arrest in the G0/G1 phase and down-regulation of cyclinD1 and cyclin E, and up-regulation of p27kip1. We also showed that tangeretin inhibitedthe PDGF-BB-induced phosphorylation of AKT, while had no effect on the activation ofphospholipase Cγ(PLCγ1), PDGF receptor β-chain (PDGF-Rβ), and ERK1/2, JNK andp38 mitogen-activated protein kinases (MAPKs). Taken together, these findings suggestthat tangeretin could suppress PDGF-BB-induced proliferation and migration of RASMCsthrough the suppression of PI3K/AKT signaling pathway, and may be a potentialcandidate for preventing or treating vascular diseases, such as atherosclerosis andrestenosis.D-17-06Effect of the ethanolic extract from Schizandra Chinensis onspermatogenesisSung-Kwang Yoo, Dong-Hyun Suh and Si-Kwan KimDepartment of Life Science, Konkuk University, Chungju-city, Chungbuk Pref. 380-701, KoreaSchizandra Chinensis is such an herbal medicine that has been widely used not only inChina for the treatments of dyspnea, cough, mouth dryness, spontaneous diaphoresis,nocturnal diaphoresis, nocturnal emission, dysentery, insomnia, and amnesia but alsowidely used in the United States as a dietary supplement. However, no report has beenelucidated it’s spermatogenesis effect. Schizandra Chinensis was extracted with 100%ethanol three times in reflux system. Schizandra Chinensis ethanol extract (SCEE) hadbeen used to explain spermatogenesis effect in our experiments. Effect of Nectin-2, Prx-3and inhibin-αin spermatocyte GC-2pd(ts) cell showed no change by stimulation with 200μM hydrogen peroxide. Interestingly, they were considerably regulated by SCEE. Effect ofNectin-2, Prx-3 and inhibin-αin spermatocyte leydig TM3 cell showed no change bystimulation with 200 μM hydrogen peroxide. Interestingly, SCEE dose-dependentlyameliorated of nectin-2 and Prx-3. Effect of apigenin in sertoli TM4 cell was that theexpreessions of nectin-2 and Prx-3 were completely attenuated by hydrogen peroxide.SCEE dose-dependently ameliorated of nectin-2 and Prx-3. These results show thatSCEE leads us to expect the further development of drugs relation spermatogenesis.218 Korean Society for Biochemistry and Molecular Biology