• Journal of Applied Biological Chemistry
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• 제66권
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• pp.165-170
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• 2023

Isolation of the culture broth of a marine-derived Acremonium sp. CNQ-049 guided by HPLC-UV yielded compound 1 (3-phenethyl-2-phenylquinazolin-4(3H)-one), and its inhibitory activities against monoamine oxidases (MAOs), cholinesterases (ChEs), and β-secretase 1 (BACE1) were evaluated. Compound 1 was an effective selective MAO-B inhibitor with an IC₅₀ value of 9.39 µM and a selectivity index (SI) value of 4.26 versus MAO-A. In addition, compound 1 showed a potent selective butyrylcholinesterase (BChE) inhibition with an IC₅₀ value of 7.99 µM and an SI value of 5.01 versus acetylcholinesterase (AChE). However, compound 1 showed weak inhibitions against MAO-A, AChE, and BACE1. The Ki value of compound 1 for MAO-B was 5.22±1.73 µM with competitive inhibition, and the Ki value of compound 1 for BChE was 3.00±1.81 µM with mixed-type inhibition. Inhibitions of MAO-B and BChE by compound 1 were recovered by dialysis experiments. These results suggest that compound 1 is a dual-functional reversible inhibitor of MAO-B and BChE, that can be used as a treatment agent for neurological disorders.

• 한국환경성돌연변이발암원학회지
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• 제7권2호
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• pp.72-84
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• 1987

어미쥐에 유발시킨 납중독이 새끼쥐의 특정 중추신경계에 미치는 신경독성의 선택성 여부를 알아보고자 하였다. 특정 신경계의 한 예로 모노아민성 신경계를 선택하여 납중독의 지표로 모노아민성 신경계의 효소인 MAO(monoamine oxidase)의 활성을 측정하였으며 비특정조직에의 지표로 Na+.K+-ATPase의 활성을 측정하였다. 임신한 Wistar계 어미쥐에게 임신전기간에 걸쳐 0.05 혹은 0.2% 초산납(PbAc2)용액을 식수로 공급하여 간접적으로 태아에 납중독을 유발시켰다. 새끼쥐는 출생직후 정상 식수를 공급해 주었다. 2, 4, 6 및 8주된 새끼쥐의 MAO 및 Na+.K+-ATPase활성을 대뇌, 간뇌, 중뇌, 뇌교-연수 및 소뇌 등 다섯부위에서 각기 측정하였다.

• Natural Product Sciences
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• 제16권2호
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• pp.75-79
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• 2010

Two new benzylated flavonoids, 5,7,4'-trihydroxy-6-p-hydroxybenzylflavanone (1) and 5,7,4'-trihydroxy-6,8-di-p-hydroxybenzylflavanone (2) together with six known flavonoids, kaempferol (3), artocarpesin (4), cycloartocarpesin (5), cudraflavone D (6), gericudranin E (7), and leachianone G (8) have been isolated from the root bark of Cudrania tricuspidata. The structures of 1 and 2 were characterized based on spectroscopic data including 1D- and 2D-NMR. All the isolates were evaluated for their inhibitory effects of monoamine oxidase (MAO). Among them, kaempferol (3), artocarpesin (4), and cudraflavone D (6) showed moderate inhibitory effects with $IC_{50}$ values of 82.3, 30.8, and $71.8\;{\mu}M$, respectively.

• Natural Product Sciences
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• 제19권1호
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• pp.8-14
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• 2013

The inhibitory effect and the structure-activity relationships of luteolin and its related derivatives isolated from Taraxacum mongolicum against MAO activities were investigated. The activity-guided isolation of extract from Taraxacum mongolicum led to the isolation of three flavonoids, luteolin, diosmetin, and luteolin-7-glucoside, a polyphenol, chlorogenic acid, a tyrosine and a uridine. The inhibitory activities of luteolin and its related derivatives against MAOs activities are dependent on their molecular structures. The presence of the phenolic hydroxy group at para-position is the active site for MAO-A inhibition as well as of MAO-B. The methoxy group has no potential on MAO-A inhibition. An additional phenolic hydroxy group at the ortho-position alleviates about 4-fold MAO-A inhibitory activity of phenolic hydroxy group at para-position. A carboxylic group seems to be critical for DBH inhibition and has no effects on MAO.

• 한국연초학회지
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• 제19권2호
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• pp.136-144
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• 1997

Cigarette smoking is known to suppress both 1-methy14-phenyl-155,Ltetrahydropy-ridine (MPTP)-induced parkinsonism and idiopathic Parkinson's disease (PD). However, the precise mechanism underlying its protective action against PD is not clearly elucidated yet. In order to find possible clue on the mechanism of protective action of smoking, we investigated the inhibitory effect of cigarette smoke components on rat brain mitochondria1 monoamine oxidase B (MAO-B), responsible enzyme for the activation of MPTP to its toxic metabolitesr and identified the components having an inhibitory potency on this enzyme from cigarette smoke. Total 31 eligible constituents including nicotine were selected from cigarette smoke condensates via solvents partitioning and silica gel chromatographic separation, and inhibitory potencies of 19 components on MAO-B were determined. Hydroquinone and methylcatechol, the phenolic components, showed the strongest inhibitory potencies on MAO-B activity in the components tested. 3,4-Dihydroxybenzylamino, myosmine and indole in basic fracton, eugenol in phenolic fraction, and farnesol in neutral fraction also inhibited the enzyme activity dose-dependently. Among tobacco alkaloids tested only myosmine was effective for the inhibition of this enzyme. These results suggest that the decrease in MAO-B activity by such components derived from cigarette smoke seems to be related to the suppression of MPTP-induced neurotoxicity and to the less incidence of Parkinson's disease in smokers than in nonsmokers.

• 약학회지
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• 제38권6호
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• pp.791-794
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• 1994

Sixteen kinds of naturally occurring phenolic compounds including 5 stilbenes, 7 flavonoids and 4 anthraquinones were examined in the inhibitory activity against rat liver AADC(aromatic L-amino acid decarboxylase) in vitro, using 5-hydroxytryptophan as a substrate. Three hydroxystilbenes, resveratrol 1, rhapontigenin 3 and piceatanol 5, which were known to be monoamine oxidase A inhibitors, exhibited a significant inhibition against AADC($IC_{50}$=20, 8 and $5\;{\mu}M$, respectively). By the comparison of the activity of each phenolic compound, it was suggested that the 3',4'-dihydroxyphenyl group of stilbenes or flavones was the best pharmacophore for the AADC inhibitory activity.

• 생명과학회지
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• 제16권2호
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• pp.266-273
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• 2006

MPTP에 의해 유도된 Parkinsonism에 대한 selenium의 보호효과와 그 보호작용에 대한 항산화적 해독기전을 조사하기 위하여 MPTP 10mg/kg을 6일간 주사하고 selenium (25, 50, 100 ${\mu}g/kg$)을 10일간 경구 투여하였으며 처음 6일간은 selenium와 MPTP를 병용 투여하였다. 실험동물을 마지막으로 selenium을 투여하고 24시간 후에 치사시켜 일반적인 독성과 항산화 방어능과 관련된 지표성분과 monoamine oxidase와 같은 신경생화학적인 지표성분들을 뇌조직에서 측정하였으며 그 결과 다음과 같은 결론을 얻었다. 우선 MPTP를 투여함에 따라 운동능력이 저하되던 것이 selenium을 투여함에 따라 운동능력이 증가되었으며, 이러한 결과의 기전은 selelnium을 투여함으로써 MPTP를 $MPP^+$로 대사시키는 MAO-B의 활성을 억제하였으며 $MPP^+$에 의해 유도된 신경독성에 대한 selenium의 보호 효과는 selenium을 투여함으로써 활성산소 해독계인 SOD, catalase, glutathione peroxidase의 활성을 증가시키기 때문인 것으로 사료된다.

• 대한한방내과학회지
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• 제21권2호
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• pp.275-281
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• 2000

Object : This study was carried out to examine the effect of Bupleuri Radix on experimental cholestasis, and make clear apart of this mechanism. Methods : Two models of common bile duct ligation group and taurocholate load group after common bile duct ligation were induced, and Bupleuri Radix extract was taken orally for 14 days. In the 1, 2, 4, 7 and 14 days after treatment, the mitochondrial and microsomal monoamine oxidase(MAO) A and B activities in liver were measured. Results : The mitochondrial MAO A and B activities increased in both Blupleuri Radix treated group after common bile duct ligation and Blupleuri Radix treated group after taurocholate load and common bile duct ligation. MAO A increased in Blupleuri Radix treated group after taurocholate load and common bile duct ligation, and MAO B increased in Blupleuri Radix treated group after common bile duct ligation. The microsomal MAO A activities increased in both Blupleuri Radix treated group after common bile duct ligation and Blupleuri Radix treated group after taurocholate load and common bile duct ligation. Conclusion : According to the result, it is consider that Blupleuri Radix not only improves cholestatis in liver, but also decreases a genetic synthesis of taurocholic acid.

• 한국잠사곤충학회지
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• 제42권2호
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• pp.120-125
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• 2000

This study was designed to investigate the effects of silk fibroin (Mw 500) powder (SFP) on lipofuscin, acetylcholine (ACh) and its related enzyme activities in brain of rats. Sprague-Dawley (SD) male rats (160$\pm$10 g) were fed basic diet (control group), and experimental diets (SFP-2.5 and SFp-5.0 groups) added 2.5 and 5.0 g/kg BW/day for 6 weeks. In case of liver membranes, lipofuscin (LF) levels resulted in a considerable decreases (11.5% and 13.8%, respectively) in SFP-2.5 and SFP-5.0 groups compared with control group. But in case of brain as the most sensitive organ, LF levels were remarkably inhibited about 18.3% and 21.7% in SFP-2.5 and SFP-5.0 groups compared with control group. Acetylcholine (ACh) levels were considerable decrease (3.0% and 9.2%, respectively) in brain membranes of SFP-2.5 and SFP-5.0 groups compared with control group. choine acetyltranferase (ChAT) activities as a synthesis enzyme of ACh, and acetylcholinesterase (AChE) activities as a hydrolysis enzyme resulted in a slight increases (2.4% and 3.0%, 4.6% and 6.3%, respectively), but significance difference between ChAT and AChE activities by SFP administration could be not obtained. Monoamine oxidase-B (MAO-B) activities were significantly inhibited (9.5% and 12.6%, respectively) in brain of SEP-2.5 and SFP-5.0 groups compared with control group. These results suggest that inhibiting effects of LF accumulation and MAO-B activity of silk fibroin(SFP) may play a pivotal role in protecting learning memory impairments by attenuating a various age-related changes for improvement of brain function.

• Archives of Pharmacal Research
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• 제19권1호
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• pp.23-29
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• 1996

Changes in dopaminergic activities were investigated after the intracerebroventricular (icv) administration of ethylcholine aziridium (AF64A) in rats. The levels of dopamine (DA) and metabolites, the activities of tyrosine hydroxylase (TH) and monoamine oxidase (MAO), and the specific binding sites of dopamine receptros in striata, hippocampus, and frontal cortex were assessed 6 days after the AF64A treatment with 3 nmol/each ventrcle. In frontal cortex, the levels of DA and metabolities were significantly decreased without changes in metabolites/DA ratios in the AF64A-treated groups. In contrast, the ratios of metabolites/DA were significantly decreased in striatum and hippocampus in the AF64A treatment. The activity of TH in frontal cortex was significantly decreased. However, that in other areas was not changed. Also the activity of MAO-A was not changed in the studied brain regions. However, the activity of MAO-B in striatum was significantly increased with no change in other areas. The specific binding sites of dopamine D1 and D2 receptors were increased in AF64A-treated frontal cortex. However, those were not changed in striatum and hippocampus except the small decreased specific binding sites of dopamine D-1 receptors in striatum after AF64A treatment. These results indicate that the dopaminergic activity was altered in AF64A treatment. Furthermore, it suggest that the decreased dopaminergic activities in each brain regions might be differently affected by AF64A treatment.