• 제목/요약/키워드: Metabolites

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식의약소재 천연자원으로부터 유효성분 규명 연구 (Isolation and Identification of Active Components from Natural Products)

  • 이영근;백남인;강세찬
    • 한국자원식물학회:학술대회논문집
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    • 한국자원식물학회 2021년도 춘계학술대회
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    • pp.10-10
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    • 2021
  • Natural products have been used as drugs and cosmetics due to their bioactivity and their biochemical diversity. Natural products usually refer to secondary metabolites produced by various living organisms including marine animals, insects, microbes, amphibians, and plants. These secondary metabolites, which usually have molecular weights less than 2,000 amu, are unnecessary for survival, development, growth, and reproduction but play major roles in plant defense systems against other species. These secondary metabolites such as lignans, flavonoids, monoterpenes, and phenylethanoid glycosides showed various biological activities like anti-oxidant behavior, anti-cancer properties, neuroprotective properties, and so forth. Thus, isolation and elucidation of secondary metabolites from living organisms is of great significance to human life.

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Hydrophillic Interaction Chromatography-tandem Mass Spectrometry Method for Identification and Quantitation of 5-MeO-DIPT and its Metabolites in Rat Urine

  • Kim, Yoon;Kim, Un-Yong;In, Moon-Kyo;Lee, Jae-Ick;Kwon, Oh-Seung;Yoo, Hye-Hyun
    • Bulletin of the Korean Chemical Society
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    • 제32권4호
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    • pp.1158-1164
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    • 2011
  • 5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT), a psychoactive tryptamine derivative, is a hallucinogenic drug of abuse. In this study, 5-OH-DIPT and its metabolites were identified and the quantitative method was developed and validated by using hydrophilic interaction chromatography-tandem mass spectrometry (HILICMS/MS). Chromatographic separation was achieved on an Atlantis HILIC silica column ($5{\mu}m$, $100{\times}2.1\;mm$). The metabolites of 5-MeO-DIPT in rat urine were characterized via Q1 scanning and product ion scanning. As a consequence, 5-MeO-IPT, 5-OH-DIPT, 6-OH-5-MeO-DIPT and their glucuronide conjugates were detected and identified as the metabolites of 5-MeO-DIPT. Subsequently, a quantitative method for 5-MeO-DIPT and its major metabolites, 5-MeO-IPT and 5-OH-DIPT, was developed in multiple reactions monitoring (MRM) mode. The calibration curves for all analytes evidenced good linearity over the concentration range of 1-1000 ng/mL with linear correlation co-efficients ($r^2$) in excess of 0.99. The intra- and inter-day accuracy and precision were 92.2-110.2% and 1.5-9.9%, respectively.

LC-MS/MS를 이용한 인체시료 중 프탈레이트 대사체 동시분석법 확립 (Development and Validation of On-line Column Switching HPLC-MS/MS Method for 10 Phthalate Metabolites in Human Urine)

  • 홍순근;남혜선;정기경;강일현;김태성;조상은;정수희;이장우;김준철;고영림;강태석
    • 한국환경보건학회지
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    • 제36권6호
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    • pp.510-517
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    • 2010
  • Phthalates, such as di (2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) have been proved to be teratogenics and endocrine disruptors, metabolized rapidly and excreted in the urine. In this study, a simultaneous analytical method for 10 phthalate metabolites, MnBP, MiBP, MBzP, MCHP, MEHP, MEHHP, MEOHP, MnOP, MiNP and MiDP, in human urines, based on switching system with on-line pretreatment column using HPLC-MS/MS has been developed. This method was validated according to the guideline of bioanalytical method validation of National Institute of Toxicological Research. Limits of detection range between 0.2 and 0.9 ng/ml for 10 phthalate metabolites. The calibration curves showed linearity in the range 0.997~0.999, and the results of the intra- and inter-day validations were in the range from 0.4 to 14.7% RSD and from 0.3 to 9.4% RSD, respectively. Recoveries of phthalate metabolites varied from 87.0 to 116.1%. This analytical method showed high accuracy and stable precision for all metabolites, and seems to be suitable for biomonitoring of phthalates in human urine.

루틴 대사체의 미백 효능 (Potent whitening effects of rutin metabolites)

  • 김지혜;강남주
    • 한국식품저장유통학회지
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    • 제22권4호
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    • pp.607-612
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    • 2015
  • 본 연구는 rutin 및 rutin 대사체인 DHPAA, HPAA, DHT, HVA가 버섯 유래 tyrosinase 활성과 마우스 피부표피 세포주인 JB6 P+ 세포의 증식에 미치는 영향에 대해 살펴보았다. HVA가 버섯유래 티로시나제 저해활성이 가장 우수한 것으로 관찰되었으며, DHPAA, HPAA, rutin, DHT 순서로 저해효능을 나타내었다. DHT를 제외한 rutin 및 rutin 대사체들 모두 $100{\mu}M$ 까지 세포 독성이 관찰되지 않은 것으로 관찰되었으며, DHT는 50 또는 $100{\mu}M$에서 세포증식을 저해하였으나 그 이하의 농도에서는 세포독성을 유도하지 않았다. 따라서 본 연구결과, rutin 대사체 모두 세포 독성이 없는 수준에서 버섯 유래 티로시나제 활성을 효과적으로 억제하였으므로, 앞으로 미백제제로 활용될 수 있을 것으로 기대된다.

Assessment of Di (2-ethylhexyl) Phthalate Exposure by Urinary Metabolites as a Function of Sampling Time

  • Park, Moon-Seo;Yang, Yun-Jung;Hong, Yeon-Pyo;Kim, Sang-Yon;Lee, Yong-Pil
    • Journal of Preventive Medicine and Public Health
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    • 제43권4호
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    • pp.301-308
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    • 2010
  • Objectives: In most DEHP exposure assessment studies, single spot urine sample was used. It could not compare the exposure level among studies. Therefore, we are going to represent the necessity of selection of proper sampling time of spot urine for assessing the environmental DEHP exposure, and the association urinary DEHP metabolites with steroid hormones. Methods: We collected urine and plasma from 25 men. The urine sampling times were at the end of the shift (post-shift) and the next morning before the beginning of the shift (pre-shift). Three metabolites of DEHP {mono(2-ethylhexyl) phthalate [MEHP], mono-(2-ethyl-5-hydroxyhexyl)phthalate [MEHHP], and mono(2-ethyl-5-oxohexyl)phthalate [MEOHP]} in urine were analyzed by HPLC/MS/MS. Plasma luteinzing hormone, follicle stimulating hormone, testosterone, and $17{\beta}$- estradiol were measured at pre-shift using a ELISA kit. A log-transformed creatinine-adjusted urinary MEHP, MEHHP, and MEOHP concentration were compared between the post- and pre-shift. The Pearson’s correlation was calculated to assess the relationships between log-transformed urinary MEHP concentrations in pre-shift urine and hormone levels. Results: The three urinary metabolite concentrations at post-shift were significantly higher than the concentrations in the pre-shift (p<0.0001). The plasma hormones were not significantly correlated with log-transformed creatinine - adjusted DEHP metabolites. Conclusions: To assess the environmental DEHP exposure, it is necessary to select the urine sampling time according to the study object. There were no correlation between the concentration of urinary DEHP metabolites and serum hormone levels.

Metabolism of YH1885 by Rat, Dog, Monkey and Human Liver S9 Fractions

  • Kim, Eun-Joo;Roh, Jung-Koo;Green, Carol
    • Biomolecules & Therapeutics
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    • 제6권3호
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    • pp.283-288
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    • 1998
  • YH 1885 (5,6-dimethyl -2-(4-fluorophenylamino)-4-(1-methyl -1,2,3,4-tetrahydroisoquinolin -2- yl) pyrimidine hydrochloride) was developed as an antiulcer drug. The objective of this study was to examine a comparative metabolism of YH1885 in rat, dog, monkey and human liver tissues and to determine the metabolite profiles produced by the four species. YH1885 was metabolized by liver 59 fractions from all four species. Control incubations containing 59 fraction but no cofactors, contained essentially no metabolites. Metabolism of YH1885 apparently became saturated in the concentration range studied because the % of YH 1885 metabolized decreased with increasing drug concentration for all four species. Six to nine metabolite peaks were detected in the incubations and the particular profile of metabolites varied with species. The total amount of metabolites formed by liver microsomes from human and monkey were less than microsomes from rat or dog. The major metabolite peak formed by rat liver 597actions fluted near the solvent front on the HPLC or remained at the origin in TLC, indicating that it contained one or more polar metabolites. Dog liver 59 fractions incubations contained four major metabolites that each accounted for about 15 to 20 % of the total radioactivity at the low concentration of YH1885. The metabolite profiles of YH1885 appeared to be similar in incubations with rhesus monkey and human liver 59 fraction. The amount of metabolites formed by rhesus monkey liver preparations was greater than that of human liver that contained prominent metabolite peaks with approximate relative retention time of 0.14 and 0.43.

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A Review on Venom Enzymes Neutralizing Ability of Secondary Metabolites from Medicinal Plants

  • Singh, Pushpendra;Yasir, Mohammad;Hazarika, Risha;Sugunan, Sunisha;Shrivastava, Rahul
    • 대한약침학회지
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    • 제20권3호
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    • pp.173-178
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    • 2017
  • Objectives: Medicinal plants are vital sources of bioactive compounds that are useful for the treatment of patients with snake bites or are indirectly applicable for boosting the effects of conventional serum therapy. These plants are being used traditionally by local healers and tribes for the treatment of patients with snake bites and therefore can be used as an alternative against snake envenomation. Scientifically, using the secondary metabolites of plants to neutralize venom enzymes has an extra benefit of being based on traditional knowledge; also, the use of such metabolites for the treatment of patients with snake bites is cheaper and the treatment can be started sooner. Methods: All the available information on various secondary metabolites exhibiting venom neutralizing ability were collected via electronic search (using Google books, Pubmed, SciFinder, Scirus, Google Scholar, and Web of Science) and articles of peer-reviewed journals. Results:Recent interest in different plant has focused on isolating and identifying of different phytoconstituents that exhibit Phospholipase A2 activity and other venom enzyme neutralizing ability. In this support convincing evidence in experimental animal models are available. Conclusion: Secondary metabolites are naturally present, have no side effect, are stable for a long time, can be easily stored, and can neutralize a wide range of snake enzymes, such as phospholipase A2, hyaluronidase, protease, L-amino acid oxidase, 5'nucleotidase, etc. The current review presents a compilation of important plant secondary metabolites that are effective against snake venom due to enzyme neutralization.

Determination of Adrenosterone and its Metabolites in Human Urine by LC/APCI/MS and GC/MS

  • Han, Eun-Jung;Yim, Ok-Kyoung;Beak, Sun-Young;Chung, Jae-Yeon;Lee, Ji-Hye;Kim, Jun-Gahn;Kim, Yun-Je
    • Bulletin of the Korean Chemical Society
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    • 제30권7호
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    • pp.1489-1496
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    • 2009
  • This study was done for the determination and excretion profile of adrenosterone and its metabolites in human urine using both liquid chromatography with atmospheric pressure chemical ionization mass spectrometry and gas chromatography with mass spectrometry. Adrenosterone and its two metabolites were detected in human urine after administration a healthy volunteer with 75 mg of adrenosterone. We found that adrenosterone-M1 ($C_{19}H_{26}O_3$) was a reduction and adrenosterone-M2 ($C_{19}H_{26}O_4$) was a hydroxylation at C-ring, which did not know the exact position of the C-ring. The adrenosterone parent was detected by GC/TOF-MS, but not detected by LC/APCI/MS because of low intensity. Adrenosterone and its two metabolites were excreted as their glucuronided fractions. The recovery of this method ranged from 100.7 to 118.4% and the reproducibility and accuracy test were 85.5 to 112.0% and 1.1 to 8.4%, respectively. The excretion studies showed that adrenosterone and its metabolites were detectable in human urine during a 48 h period after oral administration, with maximum level of excretion at 4.1 h. The glucuro-/sulfaconjugated ratio of adrenosterone, M1 and M2 was 0.73 ${\pm}$ 0.03, 0.96 ${\pm}$ 0.06 and 0.89 ${\pm}$ 0.03 (n = 6), respectively. The amounts of adrenosterone excreted in urine were 14.75 ng for 48 h. Also, the maximum level of androsterone and 11$\beta$-hydroxy androsterone, which were endogenous steroids, were reached 4.1 h after the oral administration of adrenosterone.

6-하이드록시도파민으로 유도된 흰주 뇌내의 도파민 고갈에 대한 $\ell$-디프레닐의 억제효과 (${\ell}-Deprenyl$ (Selegiline) Prevents 6-Hydroxydopamine-induced Depletion of Dopamine and Its Metabolites in Rat Brain)

  • 김은미;김선춘;정희선;김화정
    • 약학회지
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    • 제43권1호
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    • pp.33-41
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    • 1999
  • Whereas as selective inhibitor of monoamine oxidase type B, ${\ell}-deprenyl$ (selegiline), is now widely used in the treatment of Parkinson's disease, the precise action mechanism of the drug remains elusive. In this study, to investigate protective effect of ${\ell}-deprenyl$ against the dopamine depletion induced by 6-hydroxydopamine (6-OHDA), the changes in tissue contents of dopamine, serotonine (5-HT) and their metabolites by ${\ell}-deprenyl$ were examined in intact and 6-OHDA-lesioned rat brain. In intact rats, a single intraperitoneal (i.p.) administration of ${\ell}-deprenyl$ showed a no change in striatal dopamine and its metabolites at low concentrations (0.25 and 1 mg/kg), but significantly inhibited dopamine metabolism at a higher concentration (10 mg/kg). The repeated administration of ${\ell}-deprenyl$ (0.25 and 1 mg/kg, i.p., for 21 consecutive days) reduced the contents of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) in dose-dependent manners without changes in dopamine content. Bilateral intracerebroventricular (i.c.v) infusion of 6-OHDA ($100{\;}\mu\textrm{g}/10{\;}{\mu}{\ell}/hemisphere$) depleted dopamine in striatum and septum by 81% and 90% respectively. When rats were pretreated with ${\ell}-deprenyl$ before 6-OHDA administration, the striatal and septal dopamine levels were significantly increased by about 3.0-fold and 3.4-fold, respectively, compared to the untreated 6-OHDA-lesioned rat. Pretreatment of ${\ell}-deprenyl$ also significantly enhanced the dopmaine metabolites, DOPAC, HVA and 3-methoxytyramine, in the striatum, and DOPAC in the septum. These results indicate that a ${\ell}-deprenyl$ pretreatment prevents 6-OHDA-induced depletion of striatal dopamine and its metabolites.

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