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Inhibition of Cytochrome P450 by Propolis in Human Liver Microsomes
류창선,오수진,오정민,이지윤,이상윤,채정우,권광일,김상겸 한국독성학회 2016 Toxicological Research Vol.32 No.3
Although propolis is one of the most popular functional foods for human health, there have been no comprehensive studies of herb-drug interactions through cytochrome P450 (CYP) inhibition. The purpose of this study was to determine the inhibitory effects of propolis on the activities of CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1 and 3A4 using pooled human liver microsomes (HLMs). Propolis inhibited CYP1A2, CYP2E1 and CYP2C19 with an IC50 value of 6.9, 16.8, and 43.1 μg/mL, respectively, whereas CYP2A6, 2B6, 2C9, 2D6, and 3A4 were unaffected. Based on half-maximal inhibitory concentration shifts between microsomes incubated with and without nicotinamide adenine dinucleotide phosphate, propolis-induced CYP1A2, CYP2C19, and CYP2E1 inhibition was metabolism-independent. To evaluate the interaction potential between propolis and therapeutic drugs, the effects of propolis on metabolism of duloxetine, a serotonin-norepinephrine reuptake inhibitor, were determined in HLMs. CYP1A2 and CYP2D6 are involved in hydroxylation of duloxetine to 4-hydroxy duloxetine, the major metabolite, which was decreased following propolis addition in HLMs. These results raise the possibility of interactions between propolis and therapeutic drugs metabolized by CYP1A2.
Expression of hepatic antioxidant enzymes in non-obese type-2 diabetic Goto–Kakizaki rats
류창선,오수진,오정민,이상윤,윤강욱,이지윤,박성규,김봉희,마진열,김상겸 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.10
Diabetes mellitus and its complications havebeen attributed in part to oxidative stress, against whichantioxidant enzymes constitute a major protective mechanism. The present study was performed to investigate theeffects of early stage type 2 diabetes in the absence of obesityand liver damage on hepatic antioxidant enzyme expressionand oxidative stress using 9-week-old Goto–Kakizaki (GK)rats. Hepatic total antioxidant capacity determined by totaloxygen radical scavenging capacity and lipid peroxidationdetermined by malondialdehyde in plasma and liver were notsignificantly different between normal Wistar rats and GKrats. These results indicated that oxidative stress is not evidentin these type 2 diabetic rats. Hepatic expression levels ofantioxidant enzymes, including superoxide dismutase-1,catalase, glutathione peroxidase and reductase, thioredoxin-1, mu- and pi-class glutathione S-transferase (GST), and the gamma-glutamylcysteine ligase catalytic subunit, were notdifferent between normal rats and GK rats. But, hepatic leveland activity of alpha-class GST were decreased and peroxiredoxin-1 level was increased in GK rats, suggesting thatupregulation of peroxiredoxin-1 compensates for downregulationof alpha-class GST. These results suggest that alphaclassGST and peroxiredoxin-1 in liver can be altered duringthe early stages of type 2 diabetes in the absence of obesityand severe oxidative stress.
하이퍼텍스트를 이용한 재사용 라이브러리의 이해도 증진에 관한 연구
류창선(Chang-Seon Ryu),임근(Keun Lim),이경환(Kyung Whan Lee) 한국정보과학회 1992 한국정보과학회 학술발표논문집 Vol.19 No.2
재사용 시스템인 CARS 1.0에서 부품선택시 이해의 과정은 검색 단계에서의 이해 그리고 수정, 합성 단계에서의 이해로 나뉘어진다. 본 연구에서는 부품 선택시 이해도 증진을 위해 구현 기술로서 하이퍼텍스트를 적용하여 재사용 시스템의 한 부분인 이해 시스템을 설계, 구현 하였다. 하이퍼텍스트 기반 이해 시스템에서는 객체모델링 단계 에서의 정보와 재사용 시스템 사용시 발생하는 경험적 유의사항등을 annotation하는 기능을 제공 하므로 사용자의 부품선택시 이해의 증진을 이루고자 하는 시스템이다. 본 이해 시스템의 이해를 위해 제공하는 뷰 로서는 모델링 카드 뷰, 코맨트 뷰, 원시 코드 뷰, 상속 뷰, 그리고 계층구조 뷰가 있다.
Caffeic acid phenethyl ester의 cytochrome P450 저해 활성 평가
류창선(Chang Seon Ryu),박지은(Ji-Eun Park),김상겸(Sang Kyum Kim) 대한약학회 2018 약학회지 Vol.62 No.2
Caffeic acid phenethyl ester (CAPE) is one of the major active components of propolis showing inhibitory activ-ity against cytochrome P450 (CYP). The purpose of this study was to determine CYP inhibitory potential and metabolic sta-bility of CAPE using human liver microsomes (HLM) for characterization of its metabolic properties. Among CYP isoforms including CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4, CAPE exhibited strong inhibitory potential against CYP1A2 and 2C9, moderate against CYP2E1, 2B6, 2C8, 2C19 and 3A4, and weak against CYP 2D6 and 2A6, based on the IC 50 values. The inhibition of CYP1A2 but not CYP2C9 was increased by preincubation with CAPE and NADPH, suggesting that the CAPE-induced CYP1A2 inhibition may be metabolism-dependent. In metabolic stability study using HLM, CAPE was rapidly hydrolyzed to caffeic acid in a NADPH-independent manner. Caffeic acid exhibited week CYP inhibitory activity, relative to CAPE. These results raise the possibility that CAPE plays a role in propolis-mediated CYP inhibition.
홍삼 Ginsenoside의 Cytochrome P450 저해 활성 평가
류창선(Chang Seon Ryu),신장현(Jang Hyun Shin),신병찬(Byoung Chan Shin),심재한(Jae Han Sim),양현동(Hyeon Dong Yang),이성우(Sung Woo Lee),김봉희(Bong-Hee Kim) 대한약학회 2015 약학회지 Vol.59 No.2
In the present study we evaluated comparative herb-drug interaction potential of red ginseng total powder, ginsenoside Rg1, and Rb1 by inhibition of CYP isoforms including CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 using pooled human liver microsomes (HLMs). As measured by liquid chromatography-electrospray ionization tandem mass spectrometry, red ginseng total powder inhibited significantly activities of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and testosterone 6-beta hydroxylation by CYP3A4, but the IC50 values were higher than 556 μg/ml. Activities of CYP2B6, CYP2C9, CYP2D6 and CYP3A4 were inhibited by ginsenoside Rb1. Also, activities of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and testosterone 6-beta hydroxylation by CYP3A4 were inhibited by ginsenoside Rg1. The IC50 values of ginsenoside Rb1 and Rg1 were higher than 200 μg/ml. Based on IC50 values against CYP isoforms, ginsenosides-drug interactions by CYP inhibition may be very low in clinical situations.