오수유가 선천성고혈압흰쥐의 혈압에 미치는 영향

정수연(Soo Youn Chung),박윤주(Youn Joo Park),정면우(Myeon Woo Chung),임화경(Hwa Kyung Lim),강주희(Ju Hee Kang),최기환(Ki Hwan Choi),김주일(Joo Il Kim) 한국응용약물학회 2000 Biomolecules & Therapeutics(구 응용약물학회지) Vol.8 No.4

The present study examined the effect of a methanol extract of Evodiae Fructus on the blood pressure in spontaneously hypertensive rats (SHR). The systolic blood pressure was measured after rats were pretreated with phentolamine, propranolol, or N_ω-nitro-_L-arginine methyl ester(NAME) and subsequently received methanol extract of Evodiae Fructus. In SHR, intraperitoneal administration of methanol extract of Evodiae Fructus (0.5 mg/kg) produced antihypertensive effect that lasted for at least 4 hours. Antihypertensive effect of Evodiae Fructus was more stronger than that with α-adrenergic receptor antagonist phentolamine and was not affected by β-adrenergic receptor antagonist propranolol. The antihypertensive effect of Evodiae Fructus was abolished by pretreatment of NAME. Our findings suggest Evodiae Fructus has an hypertensive effect, which may be mediated through nitric oxide synthesis.

적출관류 간에서 대황, 마황 및 황금이 7-에톡시쿠마린의 대사에 미치는 영향

최기환(Ki Hwan Choi),김순선(Soon Sun Kim),박윤주(Youn Joo Park),정혜주(Hye Joo Chung),안미령(Mee Ryung Ahn),서수경(Soo Kyung Suh),신윤용(Yhun Yhong Sheen),김동섭(Dong Sup Kim),장영섭(Young Sup Chang) 대한약학회 1998 약학회지 Vol.42 No.4

In order to study the effects of Rhei rhizoma, Ephedrae herba and Scutellariae radix on hepatic metabolism, we examined the pretreatment effect of those on the metabolism of 7-ethoxycoumarin (EC). Water extracts (1g/kg) of Rhei rhizoma, Ephedrae herba and Scutellariae radix were administered orally to rats for 7 days, respectively. Livers were then isolated and perfused with 100mcM EC for 2 hours. The metabolites of EC, 7-hydroxycoumarin, sulfate conjugate and glucuronide conjugate were measured in the perfusates. The amount of glucuronide conjugates was decreased in Rhei rhizoma pretreated rats (p<0.01), however. 7-hydroxycoumarin was increased in Ephedrae herba pretxeated rats (p<O.OD. We examined whether the change of enzyme activity is related to the change of cytochrome P4501A1 a n d P4502B1 mRNA level in the perfused rat liver, which are responsible for EC metabolism. CYPlAl a n d CYP2B1 mRNA level was increased, which was not statistically significant with rhei rhizoma nor ephedrae herba pretreatment. We also assessed the hepatotoxicity of Rhei rhizoma. Ephedrae herba a n d Scutellariae radix. The activities of ALT and AST were assayed at 24 hours after 7 days administration. Only the ratio of ALT over AST was increased in ephedrae herba pre treated rats (p<0.05). Lipid peroxidation was increased in Rhei rhizoma treatment (p<0.05). while histopathological examination performed after liver perfusion did not show a n y difference compared with vehicle treatment. These results suggest that Ephedrae herba pretreatment increases the o-deethy-lation of 7-ethoxycoumarin in rats, which may be mediated b y CYPlAl mRNA induction.

Effects of antioxidants on the neuronal cell death

Park, Younjoo,Jeong, Wonhyung,Kang, Ju-Hee,Kim, Joo-Il,Chung, Soo Youn,Chung, Myeon Woo,Lim, Hwa-Kyung,Hwang, Onyou,Lee, Sun Hee,Choi, Ki Hwan 식품의약품안전청 2000 식품의약품안전청 연보 Vol.4 No.-

증추신경흥분꼭로 낭용피고 있는 methamphetamine(METH)은 doparnine 신경세포에서 dopandne유리를 증가시킴으로서 흥분작움, 약물의존성 등의 효과를 나타낼 뿐 아니라, dopamine 신경계에 작용하여 세포손상을 유도한다. dopamine 신경세포주인 CATH.a 세포배양을 이용한 지난해의 in uifro 연구결과 MEH에 의한 신경세포사는 apoptosis에 의한 것으로 산화성 스트레스가 관여하며, MEHfl의해 세폰밖으로 유리틴 dopamine의 산화에 의한 것으로 확인되었다. 본 실험에서는 항산화 효능을 가진 것으로 알려져 있는 물질 중 인삼의 성븐 중 하나인 ginsenos펀e Rbl, 록차의 성분인 opjgallocatechin g패ate 및 selenium, aminoguanidine과 JV-acetyl cysteine이 METH과 6-hy강oxydopamine(6-·OHDA)에 의한 신경세포독성에 보호효과를 가지는지 여부에 대하여 살펴보았다. ginsenoside Rbl의 전처치레 의하여 6-0딘DA 및 METH 투여에 의한 도파민 신경세포손상이 유의성 있게 감소되었듬을 착인하고, 녹차의 성분 중 하나인 (-)eP구allocatechin 토allate 처리에 의하여 금-OHDA에 의한 도_파민 신경세포손상이 통계적으로 유의성 있게 감소되었음을 착인하였다. iNO즈 inhibitor인 aminoguanidine이 UfETH 투여에 의한 신경세포손상을 감소시킨 결과를 얻어, METH에 의한 신경세포독성을 」:1해하는 ginsenoside Rbl의 효과가 nitric oxide 기전과 관련이 있는지 여부를 살펴럴았다. 그러나 끄nsenoside Rbl 투여가 UfETH에 의하여 증가되는 NO 유리 및 iNO를 발현 증가를 억제하지는 않f=것으로 관찰되었다. 이러한 결과는, 도파민신경세포에 대한 MEH 및 6-OHDA의 손상효과를 확인하고, finsenoside Rbl, catechins, selenium 등 천연물 유래성분과 aminoguanidine,rf-acetylcystelne이 이들 신경세포손상에 미치는 영향을 살펴보고 그 기전을 검토함으로써 도파민신경 기능장애 및 보호 기전연구의 기초자료를 제공할 수 있을 것으로 사료된다. The methamphetamine(METH) Is commonly abused for its rewarding effects, which are thought to result from dopamine release in the nucleus accumbens, and is amonoaminergic toxi(:ant that destroys dopamine terminals in uivo. Previous study from ourlaboratory showed dopamine-dependent oxidative stress was the initial event of METH-inducedneurotoxicity, by using an in uifro model of immortaEzed neuronal cetl tine, CATH.a(CNSadrenergic tyrosine hydroxylase(THf expressing). In the present study, effects of possibleantioxidants, ginsenoside Rbl, epigallocatechin 2allate, selenillm, ardnoguanidine and N-acetylcysteine were exarfed whether they have protective effort from neurotoxicity induced byafETH or 6-OHDA. Pretreatment of ginsenoside Rbl significantly reduced neurotoxicity inducedby METH and 6-OHDA. Epigallocatechin gallate also sigaificantly reduced 6-OHDA inducedneurotoldcy, whereas it did not show protective effect from TvfETH-induced toxicity in CATH.acelT- Pretreatment of aminoguanidine, a specific iNOS inhibitor, decreased cytotoxicity inducedby METH. Ginsenoside Rbl, however, Od not show any difference in METH-induced increasein iNOS nor it did affect nftric oxide release. Aminoguanidine itself also did not affect ftricoxide release nor a10s induction induced by afETH. These results suggest possible role ofginsenoside Rbl..3hd epigallocatechin gallate in protectiHg dopandnergic neurotoxicity induced byMETH or 6-OHDA and that more investigations should be done to claffy the involvement ofnitric oxide as a possible mechanism of ginsenoside Rbl against bfETH-induced nevrotoxirity.

천연물이 간대사에 미치는 영향에 관한 연구(Ⅱ)

최기환,김순선,박윤주,안미령,서수경,신윤용,김동섭,장영섭 식품의약품안전청 1997 식품의약품안전청 연보 Vol.1 No.-

천연물이 간대사에 미치는 영향페 대한 연구의 일환으로 세계 전 지역에서 널리 사용되고 잇으며 우리나라에서도 사용빈도가 높으나 간염등 간질환 유발사레가 보고되고 있는 마황, 황금 및 샐제 임상에서 이들 생약과 복합해서 자주 사용죄고 있는 대황을 선정하여, 띠들 천연물의 투여가 간 대사에 미치는 영향을 살펴보았다. 대황,마황, 황금 수침액을 1.09/kg의 용량으로 럿드에 7일간 경구 투여하고,최종투여 24시간 후 랫드의 간을 적출하였다. 간 대사에 미치는 영향을 살펴보기 위한 모질약뿔인 7-etliokycournarin을 적출간에 과관류하면서 2시간동안 일정시간 간격으로 관류액을 채취하여 생성된 7-ethoxycoumarin의 대사체인 7-hydroxycoin, glucuronide 포합체, sulfate포합체를 대조군과 배교 관찰하였다. 또한 긴독성 지표로서 혈청 ALT, AST를 측정하였으며 적출관류간에 대해 lipid peronidation 정도를 살펴보고 ÷t직병리검사를 실시하였다. 대촹 투여군에서는 7-ethoxycoumarin의 gulcuronidation이 갛소하였고fP<0.01), 마황투여군에서는 7-ethoxycoumarin의 o-deethylation이 증가하였다(P<0.01). 이러한 7-ethoxycoumariu 대사의 변화가 대황, 마황에 의한 관련 효소의 생합성 증가/감소에 의한 것인지 여부를 살펴보고자 일착로 CYPIAI, Ct'P2Bl CDHA primer를 사용하여 적출관류간 소포체에서 mRNA level을 측정하였다.마황투옥군에서 CVPIAI mRNA level의 증가가 관찰되었지만 통계적으로 유의한 차이를 나타내지는 않았다. 또한 이들 천연물에 의한 간독성 유발여부를 비교 평가한 결과 혈청 ALT 및 AST는 대조군에 비하여 유의한 차이가 없었다. 그러나 만성 간염정도를 나타내는 지표인 ALT/AST ratio는 마황 투여군에ㅓ 대조군에 비하여 유으한 차이를 나타내었고 대황투여군에서 간소포체내 lipid Peroxidation(MDA production)이 대조군에 비해 증가하였다.반면 조직학적 관찰결과는 대조군에 비하여 유의한 차이를 나타내지 않았다. 이상의 결과를 요약하면 랫드에서 대황 투여에 의해 7-ethoxycoumarin gtucuronidation이 감소되었으며, 마황 투여에 의해서 7-ethoxycoumarin의 o-deethylation은 증가되었고 마창 투여군의 경우 이러한 효소의 활성증가는 CYPIA1 induction에 의한 것일 수도 있다는 가능성을 제시하고 있다. In recent 3rears, hepatotoxicity concerned with Ephedrae herba or Scutellariae radixadmiBistration was case reported and Rhei rhizoma is commonly used with them. Tn order to study theeffect of Rhei rhizoma, Ep]ledrae herba and Scutellariae radix on hepatic metabolism, we exalnined theeffect of those pretreatment on the metabolism of 7-ethoxycoumarin(EC). Water extracts(Ig/fg) ofRhei rhiaoma, Ephedrae tterba and Scutetlariae radix were admi3tistered orally to rats for T days,respectively. Livers were t:ten isolated and perfused with 100uM EC for 2 hours. The metabolites of EC,7-hydroxycoernarin, sulfate conjugate and glucuronide conjugate, were measured in the perfusates dur-ing perfusion. The amount of glucuronide conjvgates was decreased iB ahei rhizoma pretreated rats (p <0.01) and 7-bfdroxycournarin was increased in Ephedrae herba pretreated rats(p < 0.01). To examineTrhether the change of enByme activity is related to the induction ,or inhibition of enzymes concerned,we measured the change oif CYPIAt and CYPaBl mRNA level in the perfused rat liver, which are con-sidered to be EC specifie. However, CYPIAI and CYPEBI rnRNA ilevel were not found to be changedwith Rhei rhizoma nor I]3hedrae herba pretreatmen·t. We also assessed the hepatic toxicity of Rheirhizoma,.:phedrae herba and Scutellariae radix. The activity of ALT and AST was assayed at 34hrsafter 7 dfyt ndrninistratiofl and it was not found to be changed- Only the ratio of ALT over AST was in-creased in Epedrae herbs. pretreated rats(p < 0.05), which implies possible chronic hepatitis. Lipidperoxidation was increased in Rhei rhizoma treatment(p <0.05) , while histopathological examinationperformed after liver perfusion did not show any difference compared with vehicle treatmeut. Theseresutts suggest that Ephedrae herba pretreatment increases the o-deethylation of 7- ethoxrcoumariB inrats, which Inay be mediated by CYPIAI mRNA induction.