• 셀메드
• /
• 제4권3호
• /
• pp.17.1-17.8
• /
• 2014

Herbal remedies are commonly used by patients worldwide. Because these herbal preparations share the same metabolic and transport proteins with prescribed medicines, the potential for a drug-herb interaction is substantial and is an issue of significant concern. This review paper summarizes drug-herb interactions involving inhibition or induction of cytochrome P450 enzymes, drug transporters as well as modulation of drug pharmacodynamics. An increasing number of in vitro and animal studies, case reports and clinical trials evaluating such interactions have been reported, and implications of these studies are discussed in this review. The most commonly implicated drugs in the interaction include anticoagulants, antiplatelets, immunosuppressants, anti-neoplastics, protease inhibitors, and some antidepressants. Pharmacokinetic and/or pharmacodynamic interactions of five commonly used herbal remedies (danshen, garlic, Ginkgo biloba, ginseng, and St John's wort) with these drugs are presented, with focus of discussion being the potentials for interaction, their mechanisms and clinical implications. There is a necessity for adequate pharmacovigilance to be carried out in minimizing unanticipated but often preventable drug-herb interactions.

• Archives of Pharmacal Research
• /
• 제14권2호
• /
• pp.130-136
• /
• 1991

Nicotine (100 .mu. M) was incubated with microsomes (1 mg/ml) prepared from New Zealand White rabbits. On the basis of microsomal weight, the rate of nicotine oxidation were calculated on the basis of cytochrome P-450 concentration, the specific activity of the metabolic oxidation catalyzed by lung was approximately 4 times greater than liver (6.4 vs 1, 65 nmoles nicotine oxidized. nmole cytochrome $P-450^{-1}\;min{-1})$. These studies employed several methods of altering activities of specific isozymes present in pulmonary microsomes, including the use of the isozyme2 and 6 specific inhibitor $\alpha$-methylbenzyl ABT, metabolite inhibitors, norbenzphetamine and N-hydroxyamphetamine. TCDD induction and Arochlor 1260 pretreatment. These results support the conclusion that nicotine metabolism by rabbit lung microsomes is mediated primarily by cytochrome P-450 isozyme 2.

• Toxicological Research
• /
• 제7권2호
• /
• pp.173-181
• /
• 1991

Membrane transport of brazilin was investigated i primary cultured rat hepatocytes. Brazilin was transported into hepatocytes very slowly and reached plateau at about 60 minutes. Saturation of transport process was not observed and the transport was not affected by ouabain, metabolic inhibitors, and its structural analog. The amount of brazilin transported into hepatocytes was decreased when the environmental temperature was decreased. These results suggest that brazilin might be transported into hepatocytes by simple diffusional process.

• 약학회지
• /
• 제49권4호
• /
• pp.347-354
• /
• 2005

Lipopolysaccharide (LPS) induces synthesis of several inflammatory cytokines and nitric oxide (NO). NO in brain is involved not only in the regulation of important metabolic pathways via intracellular cyclic GMP-dependent path­ways, but also in neurotoxic damage by reacting with superoxide ion leading to form peroxynitrite radical. Oxidative stress has suggested to be related to the inhibition of NO synthase/cyclic GMP pathway. OQ21 is a new fluorinated quinone compound that is recently known to have inhibitory effects on both NO synthase (NOS) and guanylyl cyclase (GC). In this study, we examined effects of OQ21, other known NOS or GC inhibitors, or an antioxidant, melatonin, on the oxidative stress produced by LPS in rat brain. Oxidative stress was observed by using the 2',7'-dichlorofluorescin diacetate to measure intra-cellular reactive oxygen species (ROS) production and by measuring the formation of thiobarbituric acid reactive substances to measure lipid peroxidation. LPS induced significant increase in both ROS produdction and lipid peroxidation in all brain regions tested (striatum, hippocampus and cortex), which were dissected 6hr after intraperitoneal administration of LPS to rats. Direct striatal injection of two NOS inhibitors, N-nitro-L-arginine methyl ester and diphenyleneiodonium, or a GC inhibitor, IH-[1,2,4]oxadiazolo[4,3-a]quinoxaline-l-one, produced no significant ROS increase. However, OQ21 enhanced ROS formation in striatal tissues from LPS-treated rats. Melatonin decreased LPS-induced ROS formation and decreased ROS formation increased by OQ21 in striatum of LPS-treated rats.

• 한국작물학회지
• /
• 제15권
• /
• pp.115-121
• /
• 1974

본시험은 통일(IR 667) 벼의 적고현상의 원인이 근본적으로는 질소 비료의 부족과 토양내에 존재하는 뿌리의 호흡억제조건(예를 들면 저온, 배수불량 등) 이 질소 흡수를 저해시키는 결과라고 보고 적고현상의 본질을 더욱 구명하기 위하여 수행한 것이다. 수도품종 통일(수원 21004)과 풍광을 질소 비료와 호흡조지제에 대한 반응으로 나타나는 황화 또는 적고엽을 비교하였는데 대사 또는 호흡조지제로서는 2,4-dinitrophenol과 황화소다, 질소 급원으로서는 황산안몬을 사용했다. 본 시험의 결과를 요약하면 다음과 같다. 1. 통일벼는 재래종인 풍광에 비해서 질소에 보다 민감한 반응을 보였으며 이는 통일이 풍과에 비하여 다량의 질소를 요구하는 품종이며 질소의 결핍시는 통일은 엽록소형성이 저해되어 풍광은 그렇지 않는데 소위 적고현상을 일으켰다. 2. 특히 2,4-dinitrophenol과 황화소다와 같은 호흡조지제가 뿌리의 질소흡수에 미치는 영향은 통일벼가 풍광 보다 현저하였으며 통일의 경우 적고현상의 전제인 심한 황화현상이 나타났다. 3. 위의 두가지 사실을 미루어 보아 통일벼의 잎에 나타나는 적고현상은 질소비료의 공급 또는 흡수부족과 엽내의 질소성분부족으로 일어나는 품종자체의 특성에서 오는 현상이라고 말할수 있다.

• 농약과학회지
• /
• 제5권3호
• /
• pp.1-11
• /
• 2001

신규 제초제 작용점의 발굴은 유전체학과 조합화학 등 새로운 기술이 등장하여 그 가능성이 높아지고 있다. 대략 $10^{30}$에서 $10^{50}$여 개의 화학물질의 합성이 가능하고 50,000여 개의 식물 유전자 지도가 완성되어 이들의 조합으로 새로운 제초제의 작용점 발굴 가능성이 높아지게 될 것이다. 즉, 고등식물이 가지고 있는 50,000여 개의 유전자 가운데 0.1%, 1.0% 또는 10%가 신규 작용점이 된다면 50, 500, 5000개의 신규 작용점을 발견할 수 있는 것이다. 신규 제초제의 개발을 위해서는 target enzyme의 선택과 결정, 저해제의 설계, 작용점까지 도달하는 과정, 대사적인 운명 등 여러가지 요인들이 검토되어야 한다. 이러한 과정에서 가장 중요한 것은 확실한 작용점의 선택에 있다. 또한 다양한 생화학적 정보를 통하여 작용점/효소의 저해로부터 고사에 이르는 과정을 이해함은 물론 보다 강력한 저해제의 합성과 살초과정을 이해할 수 있어야 할 것이다. 그 동안에는 이미 알려진 작용점을 대상으로 신규 화합물을 합성하거나 유도체를 개발하는 것이 대부분이었지만 최근에는 antisense 기법 등을 활용하여 새로운 치사관련 작용점을 찾아내는데 잠재력과 가능성을 확대시켜주고 있다. 새로운 치사관련 작용점을 발굴한 후에는 대상효소의 화학적, 생화학적 기능과 단백질의 구조를 분석하여 강력한 저해제를 설계하는데 활용하게 될 것이다. 치사관련 돌연변이체와 antisense 기법을 활용하고, 식물 생리학적 반응을 기초로 하여 리드화합물을 탐색하는 것은 새로운 접근방식이며 농약 화학적 특성을 갖는 효소 저해제들의 합성은 크게 6가지로 할 수 있다. 공통특이시얀 기질 유사체 합성, affinity labels, 자살기질체, 반응중간산물, 그리고 extraneous site inhibitors 등을 들 수 있다. 이와 같은 방법으로 후보화합물이 선발된다 하여도 실제식물에 처리하여 흡수, 이행, 대사 등에 관한 시험이 반드시 이루어져야 새로운 제초제를 탄생시킬 수 있다. 또한 약물의 전달과정과 무독화작용을 통하여 pro-herbicide에 대한 연구를 진행하게 될 것이며, 마지막으로 잡초와 작물간의 선택성이 고려되어야 효소 측이적 접근방식에 의한 신규 선택성 제초제의 개발이 성공할 수 있는 것이다.

• 약학회지
• /
• 제59권3호
• /
• pp.85-91
• /
• 2015

Highly active antiretroviral therapy (HAART) has reduced AIDS-related morbidity and mortality; however, it has been associated with metabolic abnormalities including dyslipidemia and dysglycemia depending on the regimens used. The aims of this study were to analyze the prescription patterns of antiretroviral agents and to examine the prevalence of lipid abnormalities among the prescriptions of HAART. The electronic medical records (EMR) of HIV patients were retrospectively reviewed from January 2007 to September 2012 based on our inclusion criteria. The patients who had taken HAART for at least 3 months were included in this study. The lipid profiles of patients on antiretrovirals (ARTs) were collected from his or her laboratory data, and dyslipidemia was defined as total cholesterol (TC) ${\geq}240mg/dL$ and triglycerides (TG) >200 mg/dL. Eighty-four prescriptions were discovered during the study period. Twenty-three prescriptions were the combination of two nucleoside reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI). Fifty-three prescriptions were the combination of two NRTIs and one protease inhibitor (PI) and thirty-nine prescriptions of them included a PI booster. Eight prescriptions were the combination of two NRTIs and one integrase inhibitor. The Incidence of hypertriglyceridemia among the patients receiving HAART was totally about 41.7% (2NRTIs+PI regimen vs. 2NRTIs+NNRTI regimen vs. 2 NRTIs+integrase inhibitor regimen, 52% vs. 12.5% vs. 25%), but there was no incidence of hypercholesterolemia. This study investigated that the prescription medication patterns and dyslipidemia associated with lipid abnormalities among HIV patients receiving HAART. The types of HAART prescription regimens had an effect on the occurrence of hypertriglycemia. Further studies related to metabolic abnormalities and adverse effects of HIV patients on ARTs are needed in the near future.

• 대한화장품학회지
• /
• 제20권1호
• /
• pp.25-36
• /
• 1994

Gram 음성균의 세포벽 성분인 lipopolysaccharide는 각종 세포에서의 prostaglandin 합성을 증진 시키며 이는 cyclooxygenase-2의 선택적 발현에 기인한다는 사실이 이미 보고된 바 있다. 본 연구에서는 mouse peritoneal marophage를 대상으로 하여 LPS의 prostaglandin 합성 증진 작용에 대한 특성으로 검토함으로써, COX-2에 대한 선택적 저해제 검색에 이용될 수 있는지 그 가능성을 확인코자 하였다. LPS는 peritoneal macrophage에 처리시 약 8시간 정도의 lag time을 보인 후 prostaglandin 합성을 현저히 증진 시켰으며, 이는 주로 COX 활성의 증가에 기인하는 것으로 추정되었다. 또한 LPS의 작용은 항염증제인 dexamethasone에 의해서 강하게 억제 되었으며 metabolic labeling 결과 이는 COX-2의 생합성을 억제하는데 기인하는 것으로 확인되었다. 따라서 mouse peritoneal macrophage에서의 LPS에 의한 prostaglandin 합성 증진 작용은 rat alveolar macrophage와 정성적으로 동일함을 확인할 수 있었으며, 본 실험 조건은 COX-2에 대한 선택적 저해제 검색에 응용될 수 있음을 확인 하였다. 본 실험 조건하에서 비스테로이드성 항염제인 ketoprofen의 작용을 검토한 결과 ketoprofen은 COX-1에 비교적 선택적인 저해 작용을 보이는 것으로 추정 되었다.

• Archives of Pharmacal Research
• /
• 제26권8호
• /
• pp.631-637
• /
• 2003

Chloroquine has been used for many decades in the prophylaxis and treatment of malaria. It is metabolized in humans through the N-dealkylation pathway, to desethylchloroquine (DCQ) and bisdesethylchloroquine (BDCQ), by cytochrome P450 (CYP). However, until recently, no data are available on the metabolic pathway of chloroquine. Therefore, the metabolic pathway of chloroquine was evaluated using human liver microsomes and cDNA-expressed CYPs. Chloroquine is mainly metabolized to DCQ, and its Eadie-Hofstee plots were biphasic, indicating the involvement of multiple enzymes, with apparent $K_m and V_{max}$ values of 0.21 mM and 1.02 nmol/min/mg protein 3.43 mM and 10.47 nmol/min/mg protein for high and low affinity components, respectively. Of the cDNA-expressing CYPs examined, CYP1A2, 2C8, 2C19, 2D6 and 3A4/5 exhibited significant DCQ formation. A study using chemical inhibitors showed only quercetin (a CYP2C8 inhibitor) and ketoconazole (a CYP3A4/5 inhibitor) inhibited the DCQ formation. In addition, the DCQ formation significantly correlated with the CYP3A4/5-catalyzed midazolam 1-hydroxylation (r=0.868) and CYP2C8-catalyzed paclitaxel 6$\alpha$-hydroxylation (r = 0.900). In conclusion, the results of the present study demonstrated that CYP2C8 and CYP3A4/5 are the major enzymes responsible for the chloroquine N-deethylation to DCQ in human liver microsomes.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2001년도 Proceedings of International Convention of the Pharmaceutical Society of Korea
• /
• pp.109-113
• /
• 2001

Oxidized low-density lipoprotein (oxLDL) has been shown to modulate transactivations by the peroxisome proliferator activated receptor (PPAR)$\gamma$ and nuclear factor-kappa B (NF$\kappa$B). In this study, the oxLDL signaling pathways involved with the NF$\kappa$B transactivation were investigated by utilizing a reporter construct driven by three upstream NF$\kappa$B binding sites, and various pharmacological inhibitors. OxLDL and its constituent lysophophatidylcholine (lysoPC) induced a rapid and transient increase of intracellular calcium and stimulated the NF-KB transactivation in resting RAW264.7 macrophage cells in an oxidation-dependent manner. The NF$\kappa$B activation by oxLDL or lysoPC was inhibited by protein kinase C inhibitors or an intracellular calcium chelator. Tyrosine kinase or PI3 kinase inhibitors did not block the NF$\kappa$B transactivation. Furthermore, the oxLDL-induced NF$\kappa$B activity was abolished by the PPAR$\gamma$ ligands. When the endocytosis of oxLDL was blocked by cytochalasin B, the NF$\kappa$B transactivation by oxLDL was synergistically increased, while PPAR transactivation was blocked. These results suggest that oxLDL activates NF-$\kappa$B in resting macrophages via protein kinase C- and/or calcium-dependent pathways, which does not involve the endocytic processing of oxLDL. The endocytosis-dependent PPAR$\gamma$ activation by oxLDL may function as an inactivation route of the oxLDL induced NF$\kappa$B signal. Short heterodimer partner (SHP), specifically expressed in liver and a limited number of other tissues, is an unusual orphan nuclear receptor that lacks the conventional DNA-binding domain. In this work, we found that SHP expression is abundant in murine macrophage cell line RAW 264.7 but suppressed by oxLDL and its constituent I3-HODE, a ligand for peroxisome proliferator-activated receptor y. Furthermore, SHP acted as a transcription coactivator of nuclear factor-$\kappa$B (NF$\kappa$B) and was essential for the previously described NF$\kappa$B transactivation by lysoPC, one of the oxLDL constituents. Accordingly, NF$\kappa$B, transcriptionally active in the beginning, became progressively inert in oxLDL-treated RAW 264.7 cells, as oxLDL decreased the SHP expression. Thus, SHP appears to be an important modulatory component to regulate the transcriptional activities of NF$\kappa$B in oxLDL-treated, resting macrophage cells.