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J. Fd Hyg. Safety Vol. 26, No. 4, pp. 370~376 (2011) Journal of Food Hygiene and Safety Available online at http://www.foodhygiene.or.kr 천궁추출물이고지방식이로유도된비만흰쥐의생체활성에미치는영향 허예영 하배진 * 신라대학교의생명과학대학제약공학과 Effect of Ligusticum chuanxiong Hort Extracts on the Bioactivity in High-fat diet-fed Obese Rats Ye-Young Heo and Bae-Jin Ha* Department of Pharmaceutical Engineering, College of Medical Life Science, Silla University, 1-1 San, Gwaebup-dong, Sasang-gu, Busan 617-736, Korea (Received August 11, 2011/Revised October 1, 2011/Accepted October 17, 2011) ABSTRACT - This study was performed to investigate the antioxidative effect of Ligusticum chuanxiong Hort extracts (LCE) against the hyperlipidemia of high-fat diet-fed obese rats. The rats were divided into the three groups (normal group, control group and sample group) to perform the experimental research. 1.5 ml/kg of LCE was intraperitoneally administered into the sample group for 21 days. The equal dose of 0.9% saline was intraperitoneally administered into the normal group and the control group. On day 22, they were anesthetized with ether and dissected. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) were examined in serum of rats. Superoxide dismutase (SOD) was measured in mitochondrial fraction. Malondialdehyde (MDA), catalase (CAT), and glutamate peroxidase (GPx) were determined in liver homogenate. High-fat diet markedly increased the levels of AST, ALT and MDA, significantly decreasing those of SOD, CAT and GPx. But Ligusticum chuanxiong Hort-pretreatment decreased the levels of AST, ALT, and MDA. increasing those of SOD, CAT and GPx. These results demonstrated the antioxidative effects, suggesting that LCE could be the candidate for the functional material. Key words: Ligusticum chuanxiong Hort, high-fat diet, obesity, antioxidation 최근식생활의서구화로인하여고지혈증에기인하는순환기계질환의사망률이증가하고있다 1). 암, 뇌질환, 심장병, 고혈압및당뇨병등만성적인생활습관으로인한병이증가하고, 생체방어, 질병의예방및회복, 노화방지등의건강기능성에대한관심이고조되고있으며 2,3), 만성퇴행성질환발병의급격한증가를경험하고있다 4). 이러한각종질병과노화는대사과정중에생성되는활성산소와과산화지질등의산화반응에기인하는것으로알려지면서천연물유래의여러항산화물질에대한연구가활발히전개되고있다 5-9). 특히동물성지방의과다섭취로인한동맥경화 (atherosclerosis), 심근경색 (myocardial infarction), 고혈압 (hypertension) 등과같은혈관순환계질환의발생이급증하고있는추세이다 10-11). 심혈관계질환의위험인자에는여러가지가있으나, 혈청총콜레스테롤과저밀도리 *Correspondence to: Department of Pharmaceutical Engineering, College of Medical Life Science, Silla University, 1-1 San, Gwaebup-dong, Sasang-gu, Busan 617-736, Korea Tel: 82-51-999-5466, Fax: 82-51-999-5684 E-mail: bjha@silla.ac.kr 포단백콜레스테롤 (LDL-cholesterol) 및중성지방의증가등의고지혈증이주요인자로인식되고있다 12). 콜레스테롤및중성지방식품의섭취증가는고콜레스테롤혈증과밀접한관련이있다고보고되어있으며 13), 특히동물성포화지방의과다섭취는혈청콜레스테롤수준을높여심혈관계질환을비롯한여러가지질병의발생을증가시키는위험요인이된다. 지질은필수지방산을공급하고에너지원으로서효율적인체내에너지저장원인영양소인반면, 섭취량의과잉및구성지방산비율에따라서동맥경화증이나심장순환계질환등의여러가지만성질환을일으킨다. 이러한심장질환이나동맥경화증의유발에는혈중지질조성인중성지방, 인지질, 콜레스테롤함량과혈중지단백질의농도의영향이아주큰것으로알려지고있다 14). 이러한만성퇴행성질환의원인중에산화스트레스가있는데이는체내의활성산소의증가로상승되어지며노화와당뇨, 고혈압, 암과같은여러질병의진행과관련이있다는사실이보고된바있다 15). 활성산소의생성이증가하게되면체내항산화물질이낮아져만성퇴행성질환유발과관련하여산화스트레스가증가하고항산화의활성 370

Effect of Ligusticum chuanxiong Hort Extracts on the Bioactivity in High-fat diet-fed Obese Rats 371 이낮아지게되고 free radical이생성되어생체막지질을공격한다. 그결과생체내에는지질과산화물이축적됨으로써조직내의손상및대사장해를초래하여여러가지질병을유발하게된다 16-18). 인간을비롯한모든호기성세포는산소를이용하여에너지대사를진행하며생존하고있다. 그러나생체가이용한산소중 1~3% 는생체내정상적인대사과정즉각종물리적, 화학적, 생물학적인스트레스를받아유해한활성산소종 (Reactive oxygen species : ROS) 으로변하게된다 19). 이 ROS는가장안정한형태의산소인삼중항산소 ( 3 ) 가산화, 환원과정에서환원을받아생성되는 superoxide anion radical( ), 과산화수소 (hydrogen peroxide: H 2 ), hydroxyl free radical( OH) 등이있으며, 이외에도 nitric oxide 와 nitrogen dioxide (N ), hypochlorous acid (HOCl), hypobromous acid (HOBr), peroxynitrate (ONOO ) 등이있다. 이러한유해한 ROS를 free radical이라하며, 세포는이런유해한 ROS에노출되면산화적손상을입게된다 20-22). Free radicals는인체에서강한독성으로작용하며이런 radicals의제거를목적 23) 으로한다. 사람과동물에는산화적손상을예방하거나복구하는체계를가지고있으며그종류로는 superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione S-transferase (GST), catalase (CAT) 등이있다 24). 고지혈증유도흰쥐에서지질과항산화효소에미치는작용을연구하기위하여예로부터사용해온천궁을소재로비만과항산화의상관관계를실험하였다. 천궁 ( 川芎, Cnidii Rhizoma) 의기원은우리나라와중국에서는미나리과의 Ligusticum chuanxiong Hort ( 土川芎 ), 일본에서는 Cnidium officinale Makino( 日川芎 ) 이라한다. 천궁의근경은진경, 진정, 혈압강하, 혈관확장, 항균, 항산화효과, 항진균및비타민E결핍증치료등에약효가있는중 요한약용작물중하나이다 25). 약용으로이용되는천궁의근경에는 1-2% 의정유를함유하고있으며 26), cnidilide, ligustilide, neocnidilide, butylphalide, sedanoninc acid anhydride, senkeyunolide등의성분을함유하고있는것으로보고되었다 27). 국내에서는영양, 봉화, 영주, 거창등지에서많이재배되고있으며, 약재로는천궁의뿌리부위만이용되고있다. 이에본연구에서는이러한생리활성을증진시키기위해천궁을에탄올로추출하여고지방식이를이용하여고지혈증을유도한흰쥐에서의간독성에대한보호효과를확인하였다. 천궁을투여한쥐의몸무게, 혈액학적인검사등을통해천궁의안정성에대하여유의성있는결과를얻었다. 재료및방법 실험재료본실험에사용한천궁은부산광역시부전동소재의부전시장약재상으로부터구입하였다. 천궁을증류수에세척 하고, 음지에서말린후 100% ethanol로침지시켜 4시간동안환류냉각추출한다음여과액을 evaporator를이용하여추출물을농축시켰다. 농축은최대한손실이없도록농축하여추출물을분획한후동결건조하여샘플로사용하였다. 실험동물및식이실험동물은 6주령이고몸무게가 110~120 g인 Sprague- Dawley(SD) 계수컷을샘타코 ( 주 ) 로부터구입하여이용하였다. 각실험에쓰이는쥐는 7일간적응기간을주어체중을매일일정한시간에측정하였다 (Fig. 1). 쥐에활동성을주기위해 12시간낮과밤의주기로 Auto control system 기기 (SS-2000) 를사용하여최적온도 22 ± 1 o C와최적습도인 60 ± 5% 로유지하여 3주간사육하였다. 쥐들은난괴법 (randomized complete block design) 에의해 3군으로각군당 7 마리로나누어실험하였다. 각각의그룹은정상군 (NOR: 생리식염수투여 + 정상식이 ), 식이대조군 (COND: 생리식염수투여 + 고지방식이 ), 천궁식이군 (LCED: 천궁추출 Fig. 1. Comparison of body weight of rats for 3 weeks. COND : High fat LCED : Ligusticum chuanxiong Hort ethanol extract and high fat Table 1. Experimental design of rats Sprague-Dawley male rats Experimental group diet 1st~21th day Injection sample (mg/kg body wt.) NOR (7) Normal diet 1.5 ml/kg of 0.9% saline, I.p COND (7) High fat diet 1.5 ml/kg of 0.9% saline, I.p LCED (7) High fat diet 1.5 ml/kg of LCE (100 mg/kg), I.p COND : High fat LCED : Ligusticum chuanxiong Hort ethanol extract and high fat

372 Ye-Young Heo and Bae-Jin Ha Table 2. Formulation of high-fat diet PRODUCT mg % kcal % Protein 26.2 20 Carbohydrate 26.3 20 Fat 34.9 60 Total 100 kcal/gm 55.24 Ingredient mg kcal Casein, 80 Mesh 200 800 L-Cystine 3 12 Corn Starch 0 0 Maltodextrin 10 125 500 Sucrose 68.8 275.2 Cellulose, BW200 50 0 Soybean Oil 25 225 Lard* 245 2205 Mineral Mix S10026 10 0 10 0 DiCalcium Phosphate 13 0 Calcium Carbonate 5.5 0 Potassium Citrate, 1 H 2 O 16.5 0 Vitamin Mix V10001 10 40 Choline Bitartrate 2 0 Total 773.85 4057 Formulated by E.A, Ulman, Ph. D. Research Diet, Inc. Typical analysis of cholesterol in lard = 0.95 mg/gram. Cholesterol(mg)/4057 = 232.8 Cholesterol(mg)/kg = 300.8 물투여 + 고지방식이 ) 으로표기하여실험하였다 (Table 1). 21일동안급식하고 22일째되는날 ether로마취하고개복하여장기의상태를확인하였고심장에서혈액을채취하였으며 4엽의간을전부적출하여식염수로세척하여여분의혈액을제거하였다. 그리고혈액은원심분리한후혈청을획득하여실험에사용하기전에 70 o C에보관하였고, 간역시 70 o C에서보관하여사용하였다. 고지방식이투여중앙실험동물에서고지방식이를구입하였고식이의조성은 Table 2 와같다. 간조직내 mitochondria 분획의 superoxide dismutase (SOD) 활성측정 SOD 효소활성의측정은 Beauchamp 와 Fridovich 법 29) 의변형된방법에따라 0.2M K-phosphate buffer (ph 7.4) 를 6720 µl, 1 mm xanthine 100 µl, 1% sodium deoxychlorate 300 µl, 1.5 mm KCN 300 µl, 0.2 mm cytochrome C 1500 µl 를넣은혼학액에 sample 80 µl를넣고, xanthine oxidase원액 10 µl를넣은후 Elisa (Microtiter plate reader, Molecular Devices Co., Sunnyvale, CA., USA) 를이용하여 550 nm에서의흡광도변화를 2분동안측정하였다. 효소의활성도는 superoxide dismutase standard (Sigma Co., USA) 를표준액으로사용하여비교측정하였다. 간조직중 catalse (CAT) 의활성측정 CAT 효소활성측정은 Aebi법 30) 으로측정하였다. 측정하기에앞서효소의효율에따라결과가달라지므로희석배율을정하여선측정후일정희석배율에서가장좋은효과가보이는희석배율을선택하여측정한다. 1.9 ml의 PBS (0.05M ph7.0) 와 0.1 ml의간균질화물을첨가하여잘혼합한다. 혼합한뒤 H 2 용액 1ml를첨가한뒤 Elisa (Microtiter plate reader, Molecular Devices Co., Sunnyvale, CA., USA) 를이용하여 240 nm에서 1분 30초간측정한다. CAT 활성도의표기는 U/mg protein으로하였다. Glutathione peroxidase (GPx) 활성측정 GPx 활성도의측정은 spectrometric 측정법을이용한 Lawrence 과 Burk의방법 31) 으로시행하였다. 400 µl의 PBS (0.1M, 4 mm EDTA, ph7.0) 와 sodium azid 70 µl(nan3 ; 0.01M), GSH 70 µl(0.01m), nicotinamideadenine dinucleotide phosphate 70 µl(nadph, 1.5 mm), oxidized Glutathion 20 µl (GSSG, 1.8u/ml), 360 µl 의 D.D.W에간균질화물을 10 µl 첨가한다. 이것을상온에서 1분간방치하고난뒤 100 µl 의 H 2 (5 mm) 을첨가하여반응시킨다. 그리고 340 nm에서 1 분 30초간측정 (Microtiter plate reader, Molecular Devices Co., Sunnyvale, CA., USA) 한다. GPx 활성도의표기는 U/ mg protein으로하였다. 혈액생화학용검사혈청중의 aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), HDL-cholesterol, TG 양은 dri-chem clinical chemistry analyzer (Fuji dri-chem 3500, Fujifilm, Japan) 로측정하였다. 간균질물과미토콘드리아분획물의총단백질측정단백질의정량은 Lowry법28) 으로 750 nm에서흡광도를측정하였고, 표준단백질시료로 Bovine Serum Albumin (BSA) 을사용하였다. 간조직중 malondialdehyde (MDA) 의정량간의 MDA 수치는 Ha의방법 32) 에따라 1ml의 sodium dodecyl sulfate (SDS ; 7%) 와균질화한간시료를 0.5 ml과혼합한다. 37 o C, 30분간반응시킨뒤 0.67% thiobarbituricacid 시약을 2ml 첨가하여한시간동안끓는물에서가열하였다. 가열후즉시냉각시킨뒤부탄올 5ml을첨가하고 3000rpm 에서 10분간원심분리한다. 원심분리후상층액을취하여 535 nm의파장에서흡광도를측정 (Microtiter plate reader, Molecular Devices Co., Sunnyvale, CA., USA) 하였다. 표준시약으로는 1,1,4,4-tetra-ethoxypropane를사용하

Effect of Ligusticum chuanxiong Hort Extracts on the Bioactivity in High-fat diet-fed Obese Rats 373 여검량선을측정하였다. 통계적분석본실험에대한통계적분석은 one-way ANOVA 로검정하였고유의성은 P <0.05로하였다. 통계적계산은 SPSS (SPSS Inc., Chicago, IL, USA) 통계프로그램을이용하였다. 결과및고찰 level 역시 COND군은 NOR군에비해약 1.41배정도증가하였으며, LCED군은 COND군에비해 102.91% 의감소효과를나타내었다. 고지혈증유도로 COND군의혈청중 AST, ALT level이증가한것으로보아간의기능이저하된것으로사료된다. COND군에비하여 LCED군효소 level이감소한것으로보아천궁이고지혈증으로유도로손상된간기능을회복시킬수있는작용이있는것으로사료된다. 혈청중 AST, ALT의활성변화간조직의손상은세포내부에존재하는효소가혈액으로유출되는것을측정하거나 pericentral necrosis를관찰함으로써확인할수있다. 따라서간으로부터혈액에방출된간의효소활성도측정은간손상연구에있어서가장유용한방법중의하나이며, 특히혈장중 AST, ALT 들의효소는 Keto산에 -amino 기들을보내는데, AST는 -oxaloacetate 에아미노기를전달하여 aspatate로 ALT 는 pyruvate에아미노기를전달하여 alanin으로촉매작용을한다 33). 본실험에서는고지방식이투여군은 COND군으로하고, 고지혈을유도함과동시에 20일간천궁추출물을복강투여한 LCED군의간손상정도를살펴보기위해 AST, ALT 의혈청중효소활성변화를측정하였다. 본실험에서는 Table 3의결과를얻었다. AST level에있어서 COND군은 NOR군에비해약 2.81배정도증가하였으며, LCED군은 70.01% 의상승효과를나타내었다. ALT Table 3. Effects of Ligusticum chuaxiong Hort ethanol extract on AST, ALT levels in serum Experimental group AST(U/L) ALT(U/L) NOR (7) 074.00 ± 5.00 *** 24.00 ± 1.14 *** COND (7) 208.50 ± 3.00 34.00 ± 0.70 LCED (7) 114.33 ± 3.00 ** 23.70 ± 1.41 *** LCED : Ligusticum chuaxiong Hort ethanol extract and high fat ***p < 0.001, **p < 0.01, values are mean ± SE (n = 7) 혈청중 TC, HDL-cholesterol, TG에미치는영향콜레스테롤은지질을기초로하여간에서합성되는물질이다. 이것은인체내에서는없어서는안될물질로주로세포막이나일부호르몬에영향을미친다. 그러나일부콜레스테롤은혈관에침착하여혈액의흐름을방해하고심장에무리한자극을줄수있다. HDL-콜레스테롤의경우총콜레스테롤의일부분으로존재하고있으며지방세포에서간으로지방산을운반하는역할을하여혈관내지질을제거하여인체에해를미치지않는것이지만 LDL-콜레스테롤은 HDL-콜레스테롤과반대로작용하여혈관에쌓이는현상는현강이나타나게된다 34). HDL-콜레스테롤과 LDL-콜레스테롤의비율을가지고동맥경화의수치를간접적으로알수있게된다. 그러므로 HDL-콜레스테롤은이런지질대사에서지질을세포에서간으로이동시켜주는시스템의필수요소로매우중요한역할을하는것으로알려져있다 35). 본실험결과에는 Table 4과같은결과를나타냈다. 총콜레스테롤은 COND군이 NOR군에비해약 2.15 배증가하였으며 CON과비교하였을때 LCED군은 77.56% 수치로회복하였다. HDL-콜레스테롤에있어서는 LCED군이 NOR군에비해약 2.57배감소하였으며실험군과비교하였을때 LCED군은 63.20% 수치로회복을보였다. TG는생체내에서에너지저장형태로존재하며포화지방산의섭취나포도당과잉섭취로에너지의보존을위해형태를바꾼것으로현대성인병의원인이되는물질로인식되고있으며 TG의축척으로많은질병들이증가되고있는추세이다. TG에서는 COND군이 NOR군에비해약 1.67 배감소하였으며 LCED군은 66.96% 수치로회복하였다. Table 4. Effects of Ligusticum chuaxiong Hort ethanol extract on TC, HDL-cholesterol and TG levels in serum Experimental group TC(mg/dl) HDL-C(mg/dl) TG(mg/dl) NOR (7) 113.00 ± 3.00 *** 68.83 ± 0.07 *** 38.16 ± 1.00 *** COND (7) 052.50 ± 2.00 26.70 ± 1.73 63.88 ± 1.00 LCED (7) 099.42 ± 2.00 *** 53.33 ± 2.83 *** 46.66 ± 3.00 ** LCED : Ligusticum chuaxiong Hort ethanol extract and high fat ***p < 0.001, **p < 0.01 values are mean ± SE

374 Ye-Young Heo and Bae-Jin Ha 이것으로고지방식으로유도된고지혈증휜쥐에서혈청중의총콜레스테롤과 TG가증가하였으며 HDL-콜레스테롤이감소하였으나 LCED에서총콜레스테롤과 TG를감소시켰으며 HDL-콜레스테롤을증가시킨것으로보아천궁이비만등지질대사이상에의한성인병에효과가있는것으로사료된다. 항산화효소활성에대한효과 Superoxide anion은호기적대사과정에서여러가지생화학적반응으로생성되며, 이것으로부터생성되는 hydroxyl radical은조직및거대분자를파괴하거나기능을상실케한다. 미토콘드리아에서의 MnSOD를포함하여세포질의 Cu ZnSOD는활성산소 ( ) 를보다반응성이약한과산화수소 (hydrogen peroxide, H 2 ) 로빠르게전환시켜산소독성을방어하는중요한기능을가진다 36). Catalase는과산화수소를물로환원시키는역할을담당하는효소로 SOD와함께체내항산화효소 system의근간을이루고있다. 일반적으로스트레스에의해각종대사가증진되어활성산소가생성되고이로인해 SOD의활성이증가될경우 catalase활성도함께증가하는것으로알려져있다 37). Catalse는세포내 peroxisomes에주로분포되어있고 H 2 농도가높을때주로작용한다 38). Glutathione은산화적인손상으로부터적혈구 (red cell) 을보호한다. 그것은 disulfide bond에의해서연결된두개의 tripeptide에의해서환원된형태 (GSH) 와산화된형태 (GSSG) 사이를순환한다. GSSG는전자근원과같은 NADPH를사용하는 flavoprotein인 glutathione reductase에의해서 GSH로환원된다. Glutathione은호기적생명체에서해로운부산물인 hydrogen peroxide와 organic peroxide와함께반응함으로써해독작용에서중요한역할을수행한다. 이반응에서촉매효소인 GPx는 selenium 원자가공유결합되어있는것이주목할만하다. 이효소는 H 2 와 lipid peroxide와같은 peroxides의다양한종류들을조절한다 39). 항산화효소계의활성은 Table 5와같은결과를나타내었다. SOD 효소활성정도는 COND군이 NOR군에비해약 1.65배정도감소하였으며, LCED군은 72.51% 의상승효과를나타내었다. LCED군이 COND군보다활성정도가증가한것으로보아천궁추출물이활성산소의생성을억제하여산소독성을감소시킴으로써손상된간조직의기능을회복시킨것으로사료된다. 간조직에서의 catalase활성정도는 LCED군은 COND군에비해 51.69% 의상승효과를나타내었다. 따라서천궁은항산화효과가높은것으로판단된다. COND군보다 LCED군이 catalase가증가된것은 LCED 군이활성산소를소거하므로써생체내대사과정에서생성된유독한과산화물로부터생체조직을보호하여손상된간조직의기능을회복시킨것으로사료된다. GPx의활성도는 COND군은 NOR군에비해약 3.57 배정도감소하였으며, LCED군은 COND군에비해 82.51% 의상승효과를나타내어 NOR군으로의회복을보였다. COND 군보다 LCED군이 GPx 활성정도가높게나타난것으로보아 LCE가활성산소에대한보호효과를나타내어활성을높이는역할을한것으로사료된다. 간조직중지질과산화물에미치는영향생체내지질과산화물은분자내에 peroxide 결합을갖는지질의총칭으로 hydroxide가일반적이며, 그외에 epoproxide, polperoxide, cyclic peroxide등지질과산화에의 Table 6. Effects of Ligusticum chuaxiong Hort ethanol extract on MDA levels in liver total homogenate MDA content in liver total homogenate Experimental group (nmol/mg protein) NOR (7) 1.14 ± 0.04 *** COND (7) 6.12 ± 0.08 LCED (7) 1.40 ± 0.04*** LCED : Ligusticum chuaxiong Hort ethanol extract and high fat ***p < 0.001, values are mean ± SE (n = 7) Table 5. Effects of Ligusticum chuaxiong Hort ethanol extract on SOD, Catalase and GPx activities in liver homogenate and mitochondrial fraction Experimental group SOD activity (mu/mg protein) Catalase activity (U/mg protein) GPx activity (mu/mg protein) Mitochondrial fraction Liver homogenate Liver homogenate NOR (7) 179.53 ± 2.87 *** 354.15 ± 4.87 *** 91.00 ± 4.09 *** COND (7) 108.19 ± 2.68 129.24 ± 5.87 25.48 ± 2.04 LCED (7) 144.49 ± 2.60*** 245.22 ± 3.54*** 79.54 ± 2.69*** LCED : Ligusticum chuaxiong Hort ethanol extract and high fat ***p < 0.001 values are mean ± SE

Effect of Ligusticum chuanxiong Hort Extracts on the Bioactivity in High-fat diet-fed Obese Rats 375 한최종산물로 MDA를생성하게된다. 본실험은간세포가지질의축적으로인하여간기능이떨어지고대사상효소의변화에따른지질과산화를측정하였다. Table 6과같이 COND군은 NOR군에비해약 5.36배정도증가하였으며, LCED군은 COND군에비해 94.72% 의감소효과를보이며강한지질과산화효과를나타내었다. 요약 본연구에서는한방에서약용으로사용하고있는미나리과에속하는천궁을에탄올추출을사용하여고지방식이에의해유발된고지혈및비만흰쥐에서의항산화활성과간보호효과에미치는영향을관찰하였다. 고지방식이에의해유도된고지혈및비만흰쥐에있어서의간손상에대한천궁추출물의보호효과를연구한결과고지방식이를먹인흰쥐의혈청 aspartate aminotransferase (AST) 와 alanine aminotransferase (ALT) 는증가되었고, 간조직의균질액에서과산화지질의최종산물인 MDA 도높게나타났다. 이와반대로천궁추출물을처치한군에서는간기능지표효소의증가를억제시켰다. 간조직의항산화효소인 SOD, catalase와 GPx의활성은고지방식이의해감소되었고, 천궁추출물의투여로인해효소활성도가증가됨을볼수있었다. 본연구를통해천연물을이용한기반연구로서향후천궁의지질개선효과와항산화효과에대한분자생물학적 조직병리학적후속연구가필요하다고사료되며이연구의결과를바탕으로천궁의항산화식품이나지질개선기능성식품소재로의활용이기대되어진다. 참고문헌 1. Kim JD, Lee YI, Kim BR, Choi YS, Lee SY. Effects of meju powder supplementation on lipid metabolism in rats fed hypercholesterolemic diet. J. Korean Soc. Food Sci. Nutr. 26, 314-318 (1997). 2. Ahmed, K. A., M. Sekaran Muniandy, and I. S. Ismail. 2009. N ε -(Carboxymethyl)lysine and Coronary Atherosclerosis- Associated Low Density Lipoprotein Abnormalities in Type2 Diabetes: Current Status. J. Clin. Biochem. Nutr. 44, 14-27. 3. Creager, M. A., T. F. Luscher, F. Cosentino, and J. A. Beckman. 2003. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: Part I. Circulation 108, 1527-1532. 18. Han, G. J., D. S. Shin, and M. 4. Kim JD, Lee YI, Kim BR, Choi YS, Lee SY. Effects of meju powder supplementation on lipid metabolism in rats fed hypercholesterolemic diet. J. Korean Soc. Food Sci. Nutr. 26, 314-318 (1997). 5. Jialal, I. and S. Grundyl. Effects of dietary supplementation with alpha-tocopherol on the oxidative modification of low density lipoprotein. J. Lipid Res. 33, 899-906 (1992). 6. Johnson, J. E., R. Walford, D. Harma, and J. Miquel. In `Free radicals, aging and degenerative disease', Alen R. Liss, N.Y. 1986. 7. Kuhnau, J. The flavonoids; a class of semiessential food components; their role in human nutrition. World Rev. Nutr. Diet 24, 117-120 (1976). 8. Vinson, J. A. and B. A. Hontz.Phenol antioxidative index: Comparative antioxidant effectiveness of red and white wines. J. Agric. Food Chem. 43, 401-403. 9. Wong, S. F., B. Holliwell, R. Richimond, and W. R. Skowroneck. The role of superoxide and hydroxyl radical in the degradation of hyaluronic acid induced by metal ions and by ascorbic acid. J. Inorganic Biochem. 14, 127-134. 1984. 1981. 10. Kim BR, Kim JD, Ham SS, Choi YS, Lee SY. Effects of spice added natto supplementation on the lipid metabolism in rats. J. Korean Soc. Food Sci. Nutr. 24, 121-126 (1995). 11. Sung IS, Kim MJ, Cho SY. Effect of Quercus acutissima CARRUTHERS extracts on the lipid metabolism. J. Korean Soc. Food Sci. Nutr. 26, 327-333 (1997). 12. Jang SJ, Park YJ. Effects of dietary fiber sources and levels on lipid metabolism in rats fed high lard diet. Korean J. Nutr. 28, 107-114 (1995). 13. Spady DK, Woollett LA, Dietschy JM. Regulation of plasma LDL-cholesterol levels by dietary cholesterol and fatty acids. Annu. Rev. Nutr. 13, 355-381 (1993). 14. Park KS. Metabolic syndrome. Korean Diabetes Journal 7, 37-44 (2006). 15. Baynes JW. Role of oxidative stress in development of complications in diabetes. Diabetes 40, 405-412 (1991). 16. Plaa GL, Witschi H. Chemicals, drugs and lipid peroxidation. Annu. Rev. Pharmacol. Toxicol. 16, 125-131 (1976). 17. Alordmann R, Ribierre C, Rouach H. Ethanol induced lipid peroxidation and oxidative stress in extrahepatic tissues. Alcohol. 25, 231-237 (1990). 18. Cha JY, Kim HJ, Cho YS. Effects of water-soluble extract from leaves of Morus alba and Cudrania tricuspidata on the lipid peroxidation in tissues of rats. J. Korean Soc. Food Sci. Nutr. 29, 531-536 (2000). 19. Sohal RS and Weindruch R. Oxidative stress, caloric retriction, and ageing. Science. 128-379 (1996). 20. Yun ZF, Sheng Y, and Guoyao W. Free radicals, antioxidants, and Nutrition. Nutrition, 18, 872-879. (2002). 21. Fredovich I. Fundamental aspects of reactive oxygen species, or what's the matter with oxygen? Ann. NY Acad. Sci. 893, 13-15 (1999). 22. Wu G, Morris SM. Arginine metabolism. Nitric oxide and beyond. Biochem. J.; 336: 1-6. 23. Gillette J.R. Formation of reactive metabolites of foreign compounds and their covalent binding to cellular constituents. American Physiological Society; (1977). 24. Trackshel G, Maines MD. Characterization of glutathione S- transferase in rat kidney. Biochem. J. 252, 127-13 (1988). 25. Hatano K, I. Nishioka and S. Iwasa. Studies on "Senkyu". I.

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