흰쥐에서 내독소의 비경구 투여가 혈청 및 간의 Monoamine Oxidase 및 Xanthine Oxidase활성 변동에 미치는 영향

곽춘식,문교철,김상철 啓明大學校 醫科大學 1991 계명의대학술지 Vol.10 No.3

The activities of the serum and hepatic monoamine oxidase (MAO), a mitochondrial marker and phase I detoxifying enzyme, were measured in order to manifest the enzymologic background of the functional changes of the hepatic mitochondria in endotoxaemia. And the aqctivities of the serum and hepatic xanthine oxidase(XO), the same phase I detoxifying enzyme, were also meausred. For administration of endotxin, a does of 5mg of endotoxin(lipopolysacharide E. coli 026: B6, from Sigma chemical company, USA) per kg of body weight was adminstered through a right external jugular vein. Then the rats were killed after3, 8 and 24 hours of injection with endotoxin to measure the activities of the avove enzymes in serum and their liver. The activities of the liver mitochondrial MAO-A and B showed a significant decrease at 8 hours after endotoxin administration. Microsomal MAO-A actibity of the liver showed a significant decrease between 3 and 24 hours and microsomal MAO-B activity of the liver showed a significant decrease only at 8 hours after endotoxin administration. Serum MAO activity was not detected in control and endotoxin-administered groups except the group of 8 hours after endotoxin administration. Cytosolic XO activity in the liver showed a significant decrease between 8 and 24 hours, but serum XO activity showed a significant increase at the same time. According to results, MAO activity in the liver showes a significant decrease due to leak of this enzyme into the blood and decreased biosynthesis of the liver. XO activity decreased in the liver but its activity increased in the serum at the same time. This result is due to the leak of XO into the blood through the damaged membrane of hepatocyte.

Inhibition of Monoamine Oxidase by Anithiactins from Streptomyces sp

( Hyun Woo Lee ),( Won Kyeong Jung ),( Hee Jung Kim ),( Yu Seok Jeong ),( Sang Jip Nam ),( Heonjoong Kang ),( Hoon Kim ) 한국미생물 · 생명공학회 2015 Journal of microbiology and biotechnology Vol.25 No.9

Monoamine oxidase (MAO) is found in most cell types and catalyzes the oxidation of monoamines. Three anithiactins (A-C, modified 2-phenylthiazoles) isolated from Streptomyces sp. were tested for inhibitory activity of two isoforms, MAO-A and MAO-B. Anithiactin A was effective and selective for the inhibition of MAO-A, with an IC50 value of 13.0 μM; however, it was not effective for the inhibition of MAO-B. Anithiactins B and C were weaker inhibitors for MAO-A and MAO-B. Anithiactin A was a reversible and competitive inhibitor for MAO-A with a Ki value of 1.84 μM. The hydrophobic methyl substituent in anithiactin A may play an important role in the inhibition of MAO-A. It is suggested that anithiactin A is a selective reversible inhibitor for MAO-A, with moderate potency, and can be considered a new potential lead compound for further development of novel reversible inhibitors for MAO-A.

Monoamine Oxidase-A Genetic Variants and Childhood Abuse Predict Impulsiveness in Borderline Personality Disorder

Nathan J. Kolla,Jeffrey Meyer,Marcos Sanches,James Charbonneau 대한정신약물학회 2017 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.15 No.4

Objective: Impulsivity is a core feature of borderline personality disorder (BPD) and antisocial personality disorder (ASPD) that likely arises from combined genetic and environmental influences. The interaction of the low activity variant of the monoamine oxidase-A (MAOA-L) gene and early childhood adversity has been shown to predict aggression in clinical and non-clinical populations. Although impulsivity is a risk factor for aggression in BPD and ASPD, little research has investigated potential gene-environment (G×E) influences impacting its expression in these conditions. Moreover, G×E interactions may differ by diagnosis. Methods: Full factorial analysis of variance was employed to investigate the influence of monoamine oxidase-A (MAO-A) genotype, childhood abuse, and diagnosis on Barratt Impulsiveness Scale-11 (BIS-11) scores in 61 individuals: 20 subjects with BPD, 18 subjects with ASPD, and 23 healthy controls. Results: A group×genotype×abuse interaction was present ( F (2,49)=4.4, p =0.018), such that the interaction of MAOA-L and childhood abuse predicted greater BIS-11 motor impulsiveness in BPD. Additionally, BPD subjects reported higher BIS-11 attentional impulsiveness versus ASPD participants ( t (1,36)=2.3, p =0.025). Conclusion: These preliminary results suggest that MAOA-L may modulate the impact of childhood abuse on impulsivity in BPD. Results additionally indicate that impulsiveness may be expressed differently in BPD and ASPD.

Monoamine Oxidase and Dopamine β-Hydroxylase Inhibitors from the Fruits of Gardenia jasminoides

( Keum Hee Hwang ),( Gun Hee Kim ),( Ji Ho Kim ) 한국응용약물학회 2012 Biomolecules & Therapeutics(구 응용약물학회지) Vol.20 No.2

This research was designed to determine what components of Gardenia jasminoides play a major role in inhibiting the enzymes related antidepressant activity of this plant. In our previous research, the ethyl acetate fraction of G. jasminosides fruits inhibited the activities of both monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B), and oral administration of the ethanolic extract slightly increased serotonin concentrations in the brain tissues of rats and decreased MAO-B activity. In addition, we found through in vitro screening test that the ethyl acetate fraction showed modest inhibitory activity on dopamine- hydroxylase (DBH). The bioassay-guided fractionation led to the isolation of fl ve bio-active compounds, protocatechuic acid (1), geniposide (2), 6`-O-trans-p-coumaroylgeniposide (3), 3,5-dihydroxy-1,7-bis(4-hydroxyphenyl) heptanes (4), and ursolic acid (5), from the ethyl acetate fraction of G. jasminoides fruits. The isolated compounds showed different inhibitory potentials against MAO-A, -B, and DBH. Protocatechuic acid showed potent inhibition against MAO-B (IC50 300 mol/L) and DBH (334 mol/L), exhibiting weak MAO-A inhibition (2.41 mmol/L). Two iridoid glycosides, geniposide (223 mol/L) and 6`-O-trans-p-coumaroylgeniposide (127 mol/L), were selective MAO-B inhibitor. Especially, 6`-O-trans-p-coumaroylgeniposide exhibited more selective MAO-B inhibition than deprenyl, well-known MAO-B inhibitor for the treatment of early-stage Parkinson`s disease. The inhibitory activity of 3,5-dihydroxy- 1,7-bis (4-hydroxyphenyl) heptane was strong for MAO-B (196 mol/L), modest for MAO-A (400 mol/L), and weak for DBH (941 mol/L). Ursolic acid exhibited signifl cant inhibition of DBH (214 mol/L), weak inhibition of MAO-B (780 mol/L), and no inhibition against MAO-A. Consequently, G. jasminoides fruits are considerable for development of biofunctional food materials for the combination treatment of depression and neurodegenerative disorders.

혈소판 Monoamine Oxidase의 활성도 측정에 관한 연구

김영훈,진성태,함건주,최미연 인제대학교 1993 仁濟醫學 Vol.14 No.1

본 연구는 각종 정신신경계 질환의 생물학적 연구를 수행하기 위한 예비단계로서 현재까지 혈소판 MAO 활성도 측정에 가장 빈번히 사용되었고 신뢰성이 인성되었던 방사면역분석법과 형광분석법 및 색소기질법 등의 3가지 측정방법간의 상관성 및 검사방법의 신뢰성을 조사하였다. 그 결과 색소기질법 등의 3가지 측정방법간의 상관성 및 검사방법의 신뢰성을 조사하였다. 그 결과 색소기질법이 방사면역분석법과 상관성이 높고 특히 방사성 물질을 다루지 않아 실험이 용이하며 분석에 소요되는 시간이 짧다는 잇점이 있어 실용성이 기대된다. Monoamine oxidase(MAO) is a major enzyme in the catabolism of the brain biogenic amines. Alternations in platelet MAO activity have been reported in patients with schizophrenia, affective disorders and some other medical disorders. Platelet MAO was kinetically evaluated by three different assay procedures with different substrates in 15 healthy subjects. Results were as follows. 1.Among the three assay procedures, the radioimmunoassay method using 14C Benzylamine as a substrate was proved to be the most precise and superior than the other two, spectrofluorometry method using Kynuramine and spectrophotometry method using p-Benzylamine-azo-β-naphtol as a substrate. 2.Correlations between Michaelis constant (Km) and maximal velocity (Vmax) values of MAO measured with radioimmunoassay using 14C-Benzylamine and spectrophotometry using p-Benzylamine-azo-β-naphtol as a substrate were significant(p<.01). 3.The coefficient of variations for the two kinetic constants of platelet MAO measured with radioimmunossay and spectrophotometry on the same day were within 10%. Our results suggest that this simple and time-saving spectrophotometry method using Benylamine or its derivatives can be useful to study the kinetic properties of platelet MAO as equally as radioimmunoassay method.

Effect of halogens on 3-[4-(dimethylamino) phenyl]-1-phenylprop-2-en-1-ones: development of a new class of monoamine oxidase-B inhibitors

Hasan Haydara Ammar,Lee Jiseong,Kumar Sunil,Alfarraj Saleh,Alharbi Sulaiman Ali,Pant Manu,Kim Hoon,Mathew Bijo 한국응용생명화학회 2024 Applied Biological Chemistry (Appl Biol Chem) Vol.67 No.-

Five dimethylamino-based chalcone derivatives (AC) were synthesized and evaluated for their inhibition degree against monoamine oxidase (MAO) enzymes. All AC compounds showed better inhibitory activity against MAO-B than that against MAO-A. AC4 showed the highest inhibitory ability with an IC 50 value of 0.020 µM, similar to that of a reference drug safinamide (IC 50  = 0.019 µM) against MAO-B, followed by AC1 (IC 50  = 0.068 µM) and AC3 (IC 50  = 0.083 µM). Substituent -F in ring A (AC4) increased the MAO-B inhibition, followed by -H (AC1), -Br (AC3), and -Cl (AC2). The selectivity index (SI) value of AC4 was high (SI = 82.00) as well as other compounds (44.41 to 98.15). AC4 was found to be a reversible inhibitor as confirmed through analysis using the dialysis method. Interestingly, AC4 was observed to be a noncompetitive MAO-B inhibitor with a rare case and with K i values of 0.011 ± 0.0036 µM. These experiments confirmed that AC4 is a reversible and potent selective inhibitor of MAO-B. Molecular docking experiments revealed that AC4 showed the highest inhibitory activity with a docking score (-9.510 kcal/mol). A study using molecular dynamics modeling revealed that the protein–ligand complex was more stable. It was observed that AC4 was non-cytotoxic in the study using L929 cell line. In conclusion, compound AC4 shows promise as a MAO-B inhibitor. Five dimethylamino-based chalcone derivatives (AC) were synthesized and evaluated for their inhibition degree against monoamine oxidase (MAO) enzymes. All AC compounds showed better inhibitory activity against MAO-B than that against MAO-A. AC4 showed the highest inhibitory ability with an IC50 value of 0.020 µM, similar to that of a reference drug safinamide (IC50 = 0.019 µM) against MAO-B, followed by AC1 (IC50 = 0.068 µM) and AC3 (IC50 = 0.083 µM). Substituent -F in ring A (AC4) increased the MAO-B inhibition, followed by -H (AC1), -Br (AC3), and -Cl (AC2). The selectivity index (SI) value of AC4 was high (SI = 82.00) as well as other compounds (44.41 to 98.15). AC4 was found to be a reversible inhibitor as confirmed through analysis using the dialysis method. Interestingly, AC4 was observed to be a noncompetitive MAO-B inhibitor with a rare case and with Ki values of 0.011 ± 0.0036 µM. These experiments confirmed that AC4 is a reversible and potent selective inhibitor of MAO-B. Molecular docking experiments revealed that AC4 showed the highest inhibitory activity with a docking score (-9.510 kcal/ mol). A study using molecular dynamics modeling revealed that the protein–ligand complex was more stable. It was observed that AC4 was non-cytotoxic in the study using L929 cell line. In conclusion, compound AC4 shows promise as a MAO-B inhibitor.

Inhibition of monoamine oxidase A and B by demethoxycurcumin and bisdemethoxycurcumin

( Seung Cheol Baek ),( Bomee Choi ),( Sang-jip Nam ),( Hoon Kim ) 한국응용생명화학회 2018 Journal of Applied Biological Chemistry (J. Appl. Vol.61 No.2

Two curcumin derivatives, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), isolated from Curcuma longa were analyzed for their inhibitory activities against two isoforms of monoamine oxidase (MAO), which is involved in the catalysis of neurotransmitting monoamines. In the study, DMC and BDMC potently inhibited human MAO-B, with IC₅₀ values of 2.45 and 2.59 μM, respectively, and both compounds showed effective inhibitory activities against human MAO-A, with IC₅₀ values of 3.24 and 3.09 μM, respectively. The inhibitory activities of the two compounds were higher than those of curcumin. The removal of the methoxy or dimethoxy groups in curcumin might increase the inhibitory activities against human MAO-A and MAO-B. The inhibited activities were recovered to almost the values of the reversible references in the dialysis experiments with DMC and BDMC. DMC and BDMC showed competitive inhibition for MAO-A and MAO-B, respectively, with K_i values of 0.91 and 0.80 μM, respectively. These results suggest that the two curcumin derivatives may be useful or lead compounds in the treatment of related disorders as potent reversible MAO inhibitors.

Potent Selective Inhibition of Monoamine Oxidase A by Alternariol Monomethyl Ether Isolated from Alternaria brassicae

( Hyun Woo Lee ),( Yeon Ji Kim ),( Sang-jip Nam ),( Hoon Kim ) 한국미생물 · 생명공학회 2017 Journal of microbiology and biotechnology Vol.27 No.2

Alternariol monomethyl ether (AME), a dibenzopyrone derivative, was isolated from Alternaria brassicae along with altertoxin II (ATX-II). The compounds were tested for the inhibitory activity of monoamine oxidase (MAO), which catalyzes neurotransmitting monoamines. AME was found to be a highly potent and selective inhibitor of human MAO-A with an IC₅₀ value of 1.71 μM; however, it was found to be ineffective for MAO-B inhibition. ATX-II was not effective for the inhibition of either MAO-A or MAO-B. The inhibition of MAO-A using AME was apparently instantaneous. MAO-A activity was almost completely recovered after the dilution of the inhibited enzyme with an excess amount of AME, suggesting AME is a reversible inhibitor. AME showed mixed inhibition for MAO-A in Lineweaver-Burk plots with a Ki value of 0.34 μM. The findings of this study suggest that microbial metabolites and dibenzopyrone could be potent MAO inhibitors. In addition, AME could be a useful lead compound for developing reversible MAO-A inhibitors to treat depression, Parkinson`s disease, and Alzheimer`s disease.

Regulation of Acetylcholine Esterase and Monoamine Oxidase in Oryzias Latipes by Carbofuran

Kim, Sung Hee,Kim, Woo Keun,Lee, Jeong-Soon,Koh, Sung Cheol,Lee, Sung-Kyu,Chon, Tae-Soo,Kim, Jong-Sang 한국환경독성학회 2003 환경독성보건학회지 Vol.18 No.1

카바메이트계 농약인 카보푸란은 어류에 대한 독성이 매우 높으며, 낮은 농도에서 어류의 척추기형이나 행동이상을 유발한다. 이러한 카보푸란의 독성기전을 밝히기 위한 일환으로 신경물질대사와 관련이 깊은 acctylcholine esterasc(AChE)와 monoamine oxidase(MAO)에 미치는 농약의 효과를 송사리(Oryzias latipes; Medaka fish)를 이용하여 평가하였다. Medaka fish에 대한 카보푸란의 반수치사농도(LC_50)는 2.5ppm이었으며, 1ppb 카보푸란에 24시간 노출된 경우, AChE 효소활성이 머리와 몸통부위에서 각각 30, 20%씩 감소되었다. 한편 MAO 효소활성은 카보푸란의 농도가 증가함에 따라 머리부위에서는 감소한 반면, 몸통부위에서는 증가하는 경향을 보였다. 특히 카보푸란의 농도가 1ppb에서도 송사리의 MAO 효소활성이 영향을 받는 것으로 나타나, 카보푸란에 의한 송사리의 행동이상은 AChE 활성뿐 아니라 MAO활성의 변화에 의한 복합적인 효과일 가능성이 높다.

Monoamine Oxidase-A Inhibitors from Medicinal Plants

Ryu, Shi-Yong,Han, Yong-Nam,Han, Byung-Hoon The Pharmaceutical Society of Korea 1988 Archives of Pharmacal Research Vol.11 No.3

Thirty kinds of medicinal plants were screened to examine inhibitory activities on rat brain monoamine oxidase A, using serotonin as a substrate. As active principles, various kinds of stilbenes were isolated from Veratri Rhizoma, Reynoutriae Radix and Rhei undulati Rhizoma, and several kinds of flavonoids from Sophorae Flos, Chrisanthemi Flos and Glycine max. Among the compounds isolated, resveratrol(I) strongly inhibited MAO-A competitively, and its $IC_{50}$ and Ki values were 2 ${\mu}M$ and 2.5 ${\mu}M$, respectively. Inhibitory potencies towards MAO-A of some stilbenes and flavonoids were also compared.