• Title/Summary/Keyword: competitive inhibition

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Protective Effect of Physostigmine and Neostigmine against Acute Toxicity of Parathion in Rats

  • Jun, Jung-Won;Kim, Young-Chul
    • Archives of Pharmacal Research
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    • v.14 no.4
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    • pp.330-335
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    • 1991
  • The effects of physostigmine and neostigmine on the parathin induced toxicity were examined in adult female rats. Physostigmine $(100\;{\mu}g/kg,\;ip)$ or neostigmine $(200\;{\mu}g/kg,\;ip)$ inhibited acetylcholinesterase (AChE) and cholinesterase (ChE) activities in blood, brain and lung when the enzyme activity was measured 30 min after the treatment. At the doses of two carbamates equipotent on brain AChE, neostigmine showed greater inhibition on peripheral AChE/ChE. The enzyme activity returned to normal in 120 min following the carbamates except in the lung of rats treated with neostigmine. Carbamates administered 30 min prior to parathion (2 mg/kg) antagonized the inhibition of AChE/ChE by parathion when the enzyme activity was measured 2 hr following parathion. Neostigmine showed greater protective effect on peripheral AChE/ChE. The effect of either carbamate on AChE/ChE was not significant 2 hr beyond the parathion treatment. Carbamates decreased the mortality of rats challenged with a lethal dose of parathion (4 mg/kg, ip) either when treated alone or in combination with atropine (10 mg/kg, ip). Lethal action of paraoxon (1.5 mg/ks ip), the active metabolite of parathion was also decreased by the carbamate treatment indicating that the protection was not mediated by competitive inhibition of metabolic conversion of parathion to paraoxon. The results suggest that carbamylation of the active sites may not be the sole underlying mechanism of protection provided by the carbamates.

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Kinetic and Thermodynamic Analysis of AChE Inhibition of Solvent Extract Fractions from Inonotus obliquus (차가버섯 용매추출분획의 Acetylcholinesterase 저해활성에 대한 동역학 및 열역학적 해석)

  • Kim, Hak-Kyu;Hur, Won;Hong, Eok Kee;Lee, Shin-Young
    • Food Engineering Progress
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    • v.15 no.4
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    • pp.289-296
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    • 2011
  • Twenty four fractions by solvent extraction and/or acid precipitation from fruit body and culture broth of Inonotus obliquus were prepared, and their inhibitory effect against acetylcholinesterase (AChE) was investigated. Among these fractions, acid (1 M HCl) precipitates from cell-free culture broth and fruit body exhibited the highest inhibitory effect on AChE in vitro. Acid precipitates inhibited AChE activity in a concentration-dependant manner and $IC_{50}$ values of both acid precipitates were 0.53 mg/mL. The inhibition pattern was general non-competitive inhibition. The energetic parameters were also determined by dual substrate/temperature design. Both acid precipitates increased the values of Ea, ${\Delta}H,/;{\Delta}G$ and ${\Delta}H^{\ast}$ decreasing the value of ${\Delta}S$ for AChE. The results implied that the acid precipitates from I. obliquus increased the thermodynamic barrier, leading to the breakdown of ES complex and the formation of products as inhibitory mechanism.

Effect of DIS Process on in vitro Physiological Functionality of Aloe vera Gel (알로에 겔의 in vitro 생리기능 특성에 미치는 삼투탈수공정의 영향)

  • Kim, Sung-A;Baek, Jin-Hong;Lee, Shin-Young
    • Food Engineering Progress
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    • v.13 no.4
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    • pp.251-261
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    • 2009
  • In vitro physiological functions such as jack bean (Canavalia ensiformis) urease inhibitory activity and retarding effect of glucose/bile acid of Aloe vera gel concentrated by the optimized DIS (Dewatering Impregnation & Soaking) process conditions were examined. Urease inhibitory activity of DIS aloes ranged from 84.6 to 94.4%, which was similar to or higher than 86.3% of fresh aloe. Also, urease inhibitory activity of DIS aloes was maintained at initial levels after heat treatment (90$^{\circ}C$, 10 min.) and drying treatment (freeze or hot air drying). Urease inhibition pattern from Lineweaver-Burk plot indicated general non-competitive inhibition, and inhibition constants ($K_{IE}$ and $K_{IES}$) of DIS aloes were 41-149 and 87-163 $\mu$L/mL, respectively. DIS(glucose) and DIS(polyethylene glycol) exhibited the highest retarding effect of glucose and bile acid. Their retarding effects were about 1.6 and 1.8 folds higher than that of fresh aloe after 0.5 and 1 hr of the dialysis, respectively. Conclusively, the above in vitro physiological functions of Aloe vera gel concentrated by DIS process suggested that aloe products treated with DIS would have the potential benefits for protection against Helicobacter pylori and reduction of blood glucose and cholesterol levels.

Tyrosinase inhibition effects of Korean edible brown, green, and red seaweed extracts

  • Ju-Won Ryu;Mi-Jin Yim;Ji-Yul Kim;Jeong Min Lee;Myeong Seok Lee;Dae-Sung Lee;Ji-Young Hwang;Kyung Tae Kim;Young-Mog Kim;Sung-Hwan Eom
    • Fisheries and Aquatic Sciences
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    • v.27 no.7
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    • pp.468-473
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    • 2024
  • The tyrosinase inhibition effects of 23 marine-derived seaweeds harvested in Korea were screened to determine their potential as skin-whitening agents. Of the 23 species initially screened, the total phenolic (TP) content of brown, green, and red seaweeds were 7.62-280.11, 5.24-62.37, and 0.63-28.76 phloroglucinol equivalents (PGE) mg/g, respectively. Brown seaweed extracts exhibited much stronger inhibitory activities than green and red seaweed extracts. Among the brown seaweeds, Ecklonia cava had the highest TP content (280.11 PGE mg/g) and the strongest tyrosinase inhibitory effect with a half maximal inhibitory concentration (IC50) value of 4.38 ㎍/mL. The kinetics of tyrosinase inhibition, analyzed by Lineweaver-Burk plots, found E. cava extract to be a non-competitive inhibitor. This study's results indicated that E. cava's inhibition of tyrosinase may have potential applications in the cosmetic industry.

Inhibition of Acetolactate Synthase from Pea by Pyrimidine Derivatives (Pyrimidine 유도체에 의한 완두 Acetolactate Synthase의 저해에 관한 연구)

  • Joo, Young A;Kim, Dae Whang;Chang, Soo Ik;Choi, Jung Do
    • Journal of the Korean Chemical Society
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    • v.41 no.6
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    • pp.304-312
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    • 1997
  • Acetolactate synthase(ALS) is the common enzyme in the biosynthetic of valine, leucine, and isoleucine, and is the target of several classes of structually unrelated herbicides, including sulfonylureas, imidazolinones, and triazolopyrimidines. In an effort to develop new and desirable herbicides, we have synthesized 4,6-dimethoxypyrimidine derivatives, and examined their inhibitory activities on pea ALS. The most active compound was found to be K11570 and $IC_{50}$ value for K11570 was 0.2 ${\mu}M.$ The inhibition of pea ALS by K11570 was biphasic, showing increased inhibition with incubation time. The K11570 showed mixed-type inhibition with respect to substrate pyruvate. Dual inhibition analysis of K11570 versus sufonylurea herbicide Ally and feedback inhibitor leucine revealed that three inhibitors were competitive for binding to ALS. The arginine modified enzyme showed decreased inhibition by K11570, sufonylurea Ally, and leucine, in constrast to, tryptophan modification did not affect on the sensitivity of ALS to the inhibitors.

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Characterization of Thiol Protease Inhibitor Isolated from Streptornyces sp. KISl3 (Streptomyces sp. KIS13 균주에서 분리한 thiol계 단백질분해효소 저해물질의 특성)

  • 김인섭;이계준
    • Microbiology and Biotechnology Letters
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    • v.18 no.5
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    • pp.501-505
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    • 1990
  • Streptomyces sp. KISl3 isolated from soil was found to produce low molecular weight thiol protease inhibitors. The protease inhibitor production was closely linked to the cell growth and regulated by growth condition. The inhibitor was purified from the culture broth through butanol extraction, silicagel 60 column chromatography, Sephadex LH-20 gel filtration and preparative HPLC. The inhibitor showed specific inhibitory activity to thiol protease such as papain, picin and bromelain. The mode of inhibition against papain to Hammersten casein as a substrate was non-competitive.

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Prediction of drug-Drug Interaction During Oral Absorption of Carrier-Mediated Compounds in Humans

  • Oh, Doo-Man;Gordon L. Amidon
    • Archives of Pharmacal Research
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    • v.17 no.5
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    • pp.364-370
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    • 1994
  • A microscopic mass balance approach has been developed to estimate the extent and rate of absorption for camier-mediated comounds. For the case competitive inhibition in the presence of an inhibitor which shares the same camier, the fraction dose absorbed (F) and absorption rate constant ($K_a$) of a drug can be calculated from its concentration profile in the intestinal lumen. Absorption parameters obtained by single-pass perfusion experiments were used in the simultaion of the absorption of some aminopenicilins. Predicted fractions dose absorbed and absorption rate constants of ampicilin and amoxicilin were significantly reduced in the presence of a 6-times higher molar dose of cyclacilin. The drug-drug interactions on the competitive absroption of camier-mediated compounds were determined with regard to F and $K_a$. Predicted decreases in F for some aminopenicilins corrlated well with decrease in the urinary recovery in humans reported in the literature. Predicted decrease in the mean absorption rate constant ($\barK_a$) explain the delays in the time of peak plasma concentration ($T_{max}$) reported in humans.

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AChE Inhibitory Effect and Antioxidative Activity of Submerged Cultured Products from Hericium erinaceum (Hericium erinaceum 액체배양 생성물의 Acetyl-cholinesterase 저해 활성과 항산화 활성)

  • Jung, Jae-Hyun;Lee, Shin-Young
    • KSBB Journal
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    • v.22 no.1
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    • pp.30-36
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    • 2007
  • The water-soluble or ethanol-soluble materials extracted from fruit bodies and cultured products (mycelium and broth) of H. erinaceum were prepared, and their inhibitory effect on acetylcholinesterase (AChE) activity from Electrophorous electricus was investigated. Inhibition of 75-85% for AChE activity at concentration of 10 mg/ml was obtained and the mechanism was due to general non-competitive inhibition. Especially, the supernatant of culture broth by ethanol treatment, exhibited a strong inhibition activity of 94% at 10 mg/ml. The samples from fruit body, mycelium and broth (supernatant and precipitate by ethanol treatment) which were extracted from H. erinaceum, were very effective to inhibit the initial stage oxidation of a linoleic acid at concentration of 0.1 mg/ml. The antioxidative activity of these samples were superior than rutin, vitamin C and tocopherol as antioxidative standards by FTC (ferric thiocyanate) method, and also showed the very strong antioxidative activity of 95% without significant difference of the samples by TBA-RS (thiobarbituric acid-reactive substance) method.

Selective Butyrylcholinesterase Inhibitors Using Polyphenol-polyphenol Hybrid Molecules

  • Woo, Yeun-Ji;Lee, Bo-Hyun;Yeun, Go-Heum;Kim, Hyun-Ju;Won, Moo-Ho;Kim, Sang-Hern;Lee, Bong-Ho;Park, Jeong-Ho
    • Bulletin of the Korean Chemical Society
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    • v.32 no.8
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    • pp.2593-2598
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    • 2011
  • Polyphenols (PPs) are known as antioxidant compounds having benign biological activities. In this paper, a series of hybrid molecules between the free or acetyl protected polyphenol compounds were synthesized and their in vitro antioxidant activity (DPPH assay) and cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] inhibition activities were evaluated. As expected, free phenolic hybrid compounds (6 and 8) showed better antioxidant activity than acetyl protected hybrid compounds (5 and 7) from DPPH assay. But the contrast result was obtained from BuChE inhibition assay. Acetyl protected hybrid compounds (5 and 7) showed better inhibition activity for BuChE than free phenolic hybrid compounds (6 and 8). Specifically, 10 (AcFA-AcFA) were shown as an effective inhibitor of BuChE ($IC_{50}=2.3{\pm}0.3{\mu}M$) and also had a great selectivity for BuChE over AChE (more than 170 fold). Inhibition kinetic studies with acetyl protected compounds (5, 7, 9, and 10) indicated that 5, 7 and 10 are a hyperbolic mixed-type inhibition and 10 is a competitive inhibition type. The binding affinity (Ki) value of 10 to BuChE is $2.32{\pm}0.15{\mu}M$.

Effect of Ginseng Total Saponin on Bovine Adrenal Tyrosine Hydroxylase

  • Kim, Hack-Seang;Zhang, Yong-He;Fang, Lian-Hua;Lee, Myung-Koo
    • Archives of Pharmacal Research
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    • v.21 no.6
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    • pp.782-784
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    • 1998
  • Ginseng total saponin (GTS) can modulate dopaminergic activity at both presynaptic and postsynaptic dopamine receptors (Kim et al, 1998). The present study investigated t he effect of GTS on the bovine adrenal tyrosine hydroxylase (TH), which catalyze L/tyrosine to DOP. GTS inhibited the bovine adrenal TH by 42.4, 51.5 and 55.3% at concentrations of 40, 80 and 100${\mu}g$/ml, respectively. The IC50 value of GTS was 77.5${\mu}g$/ml. GTS exhibited noncompetitive inhibition with a substrate L-tyrosine. The Ki value was 155${\mu}g$/ml.

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