Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 29
Filter
1.
Nutrition Research and Practice ; : 408-420, 2023.
Article in English | WPRIM | ID: wpr-977306

ABSTRACT

BACKGROUND/OBJECTIVES@#Hizikia fusiformis (HF) is a class of brown seaweeds whose active ingredients exert central nervous system protective effects, such as neuroprotection;however, the underlying mechanisms remain unknown. Given that dopamine (DA) and serotonin (5HT) are two major neurotransmitters involved in various psychiatric disorders and neuronal growth in early neurodevelopmental processes, we investigated whether HF extract could modulate the molecular expression associated with DA and 5HT transmission as well as the structural formation of neurons.MATERIALS/METHODS: in vitro cell cultures were prepared from cerebral cortical neurons obtained from CD-1 mice on embryonic day 14. Cultured cells were treated with 0.1, 1.0, or 10.0 μg/mL of HT extract for 24 h, followed by fluorescence immunostaining for DA and 5HT-related receptors and transporters and some neuronal structural formation-associated molecules. @*RESULTS@#HF extract dose-dependently upregulated the expression levels of selective DA and 5HT receptors, and downregulated the levels of DA and 5HT transporters. Moreover, HF extract increased the neurofilament light chain expression. @*CONCLUSION@#These results suggest that HF may modulate DA and 5HT transmission, thereby affecting neurodevelopment.

2.
Natural Product Sciences ; : 28-35, 2021.
Article in English | WPRIM | ID: wpr-902788

ABSTRACT

The aim of this study was to anatomize the therapeutic potential of alaternin (=7-hydroxyemodin) against inflammation, advanced glycation end products (AGEs) formation, tyrosinase, and two cyclin-dependent kinases (CDKs), CDK2 and CDK4, and compare its potency with emodin. Alaternin showed lower cytotoxicity and higher dose-dependent inhibition against lipopolysaccharide (LPS) induced nitric oxide (NO) production with half maximal inhibitory concentration (IC 50 ) of 18.68 µM. Similarly, alaternin efficaciously inhibited biotransformation of fluorescent AGEs and amyloid cross-β structure on the bovine serum albumin (BSA)-glucose-fructose system, five times more than emodin. Interestingly, alaternin also showed selective activity against CDK4 at 170 µM, whereas emodin inhibited both CDK2 and CDK4 at a concentration of 17 and 380 µM respectively. In addition, alaternin showed dose-dependent inhibitory activity against mushroom tyrosinase with inhibition percentage of 35.84 % at 400 µM. Altogether, alaternin with pronounced inhibition against inflammatory mediator (NO), glycated products formation, and targeted inhibition towards CDK4 receptor can be taken as an important candidate to target multiple diseases.

3.
Natural Product Sciences ; : 28-35, 2021.
Article in English | WPRIM | ID: wpr-895084

ABSTRACT

The aim of this study was to anatomize the therapeutic potential of alaternin (=7-hydroxyemodin) against inflammation, advanced glycation end products (AGEs) formation, tyrosinase, and two cyclin-dependent kinases (CDKs), CDK2 and CDK4, and compare its potency with emodin. Alaternin showed lower cytotoxicity and higher dose-dependent inhibition against lipopolysaccharide (LPS) induced nitric oxide (NO) production with half maximal inhibitory concentration (IC 50 ) of 18.68 µM. Similarly, alaternin efficaciously inhibited biotransformation of fluorescent AGEs and amyloid cross-β structure on the bovine serum albumin (BSA)-glucose-fructose system, five times more than emodin. Interestingly, alaternin also showed selective activity against CDK4 at 170 µM, whereas emodin inhibited both CDK2 and CDK4 at a concentration of 17 and 380 µM respectively. In addition, alaternin showed dose-dependent inhibitory activity against mushroom tyrosinase with inhibition percentage of 35.84 % at 400 µM. Altogether, alaternin with pronounced inhibition against inflammatory mediator (NO), glycated products formation, and targeted inhibition towards CDK4 receptor can be taken as an important candidate to target multiple diseases.

4.
Natural Product Sciences ; : 214-220, 2020.
Article | WPRIM | ID: wpr-836992

ABSTRACT

Brassica oleracea var. gongylodes (red kohlrabi) is a biennial herbaceous vegetable whose edible bulbotuber-like stem and leaves are consumed globally. Sliced red kohlrabi tubers were extracted using methanol and the concentrated extract was partitioned successively with dichloromethane (CH 2 Cl 2), ethyl acetate (EtOAc), n-butanol (n-BuOH) and water (H 2 O). Repeated column chromatography of EtOAc fraction through silica, sephadex LH-20 and RP-18 gel led to isolation of eleven compounds of which compound 1 was a new glycosylated indole alkaloid derivative, 1-methoxyindole 3-carboxylic acid 6-O-β-D-glucopyranoside. Others were known compounds namely, β-sitosterol glucoside (4), 5-hydroxymethyl-2-furaldehyde (5), methyl-1-thio-βD-glucopyranosyl disulfide (6), 5-hydroxy-2-pyridinemethanol (7), (3S,4R)-2-deoxyribonolactone (8), n-butyl-βD-fructopyranoside (9), uridine (10) and three fructose derivatives, D-tagatose (11), β-D-fructofuranose (12) and β-D-fructopyranose (13). Similarly, isolation from CH 2Cl 2 fraction gave two known indole alkaloids, indole 3-acetonitrile (2) and N-methoxyindole 3-acetonitrile (3). The structure elucidation and identification of these compounds were conducted with the help of 13 C and 1 H NMR, HMBC, HMQC, EIMS, HR-ESIMS and IR spectroscopic data, and TLC plate spots visualization. Compounds 2, 3, 4, 5, 6, 7, 8 and 9 are noted to occur in kohlrabi for the first time. Different bioactivities of these isolated compounds have been reported in literature.

5.
Natural Product Sciences ; : 181-199, 2019.
Article in English | WPRIM | ID: wpr-760573

ABSTRACT

Angelica decursiva Fr. et Sav. (Umbelliferae) has traditionally been used to treat different diseases due to its antitussive, analgesic, and antipyretic activities. It is also a remedy for thick phlegm, asthma, and upper respiratory infections. Recently, the leaf of A. decursiva has been consumed as salad without showing any toxicity. This plant is a rich in different types of coumarin derivatives, including dihydroxanthyletin, psoralen, dihydropsoralen, hydroxycoumarin, and dihydropyran. Its crude extracts and pure constituents possess anti-inflammatory, anti-diabetic, anti-Alzheimer disease, anti-hypertension, anti-cancer, antioxidant, anthelmintic, preventing cerebral stroke, and neuroprotective activities. This valuable herb needs to be further studied and developed not only to treat these human diseases, but also to improve human health. This review provides an overview of current knowledge of A. decursiva metabolites and their biological activities to prioritize future studies.


Subject(s)
Humans , Angelica , Apiaceae , Asthma , Complex Mixtures , Coumarins , Ethnobotany , Ficusin , Pharmacology , Plants , Respiratory Tract Infections , Stroke
6.
Natural Product Sciences ; : 326-333, 2019.
Article in English | WPRIM | ID: wpr-786427

ABSTRACT

The purpose of our study was to evaluate anti-AD potential of Cirsium maackii flowers. MeOH extract, CH2Cl2, EtOAc, and n-BuOH fraction of this flower notably inhibited BACE1 (IC₅₀ = 76.47 ± 1.66, 22.98 ± 1.45, 8.65 ± 0.63, and 72.47 ± 3.04 µg/mL, respectively). β-amyrenone (49.70 mg) (1), lupeol acetate (1.43 g) (2), lupeol (1.22 g) (3), lupenone (23.70 mg) (4), β-sitosterol (1.01 g) (6), and β-sitosterol glucoside (13.00 mg) (7) from CH₂Cl₂, apigenin (100.20 mg) (8), luteolin (19.00 mg) (9), apigenin 7-O-glucuronide methyl ester (21.30 mg) (14), and tracheloside (53.70 mg) (5) from EtOAc, apigenin 5-O-glucoside (11.00 mg) (10), luteolin 5-O-glucoside (11.00 mg) (11) and apigenin 7-O-glucuronide (91.00 mg) (12) from n-BuOH, and luteolin 7-O-glucuronide (22.00 mg) (13) from H₂O fraction were isolated. HPLC showed high levels of 8, 9 and 12 in MeOH extract (33.07 ± 0.07, 31. 44 ± 0.17 and 16.89 ± 0.33 mg/g, respectively), EtOAc (161.01 ± 1.78, 96.93 ± 0.34 and 73.38 ± 0.06 mg/g, respectively), and n-BuOH fraction (32.18 ± 0.33, 44.31 ± 0.32 and 105.94 ± 0.36 mg/g, respectively). Since, 3 and 9 are well-known BACE1 inhibitors, the anti-AD activity of C. maackii flower might be attributable to their presence.


Subject(s)
Alzheimer Disease , Apigenin , Chromatography, High Pressure Liquid , Cirsium , Flowers , Luteolin
7.
Natural Product Sciences ; : 259-265, 2018.
Article in English | WPRIM | ID: wpr-741632

ABSTRACT

The three flavone glycosides, 4′-O-methylisoscutellarein 7-O-(6‴-O-acetyl)-β-D-allopyranosyl(1→2)-β-D-glucopyranoside (1), isoscutellarein 7-O-(6‴-O-acetyl)-β-D-allopyranosyl(1→2)-β-D-glucopyranoside (3), and isoscutellarein 7-O-β-D-allopyranosyl(1→2)-β-D-glucopyranoside (4) in addition to a flavonol glycoside, kaempferol 3-O-β-D-glucopyranoside (astragalin, 2), were isolated from Stachys japonica (Lamiaceae). In cholinesterase inhibition assay, compound 1 significantly inhibited aceylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities (IC₅₀s, 39.94 µg/ml for AChE and 86.98 µg/ml for BChE). The content of isolated compounds were evaluated in this plant extract by HPLC analysis. Our experimental results suggest that the flavonoid glycosides of S. japonica could prevent the memory impairment of Alzheimer's disease.


Subject(s)
Alzheimer Disease , Butyrylcholinesterase , Cholinesterases , Chromatography, High Pressure Liquid , Glycosides , Lamiaceae , Memory , Plants , Stachys
8.
Natural Product Sciences ; : 171-180, 2018.
Article in English | WPRIM | ID: wpr-741621

ABSTRACT

Artemisia capillaris has been widely used as an alternative therapy for treating obesity and atopic dermatitis. It has been used as a hepatoprotactant. It is also used for ameliorating inflammatory reactions. Although there are several investigations on other Artemisia species, there is no systematic study describing the role of A. capillaris MeOH extract, its solvent soluble fractions, or derived anti-inflammatory principal components in regulating inflammatory conditions. Therefore, the objective of this study was to elucidate anti-inflammatory mechanisms of A. capillaris. Results revealed that MeOH extract of A. capillaris could decrease LPS-stimulated NO secretion. Of tested fractions, CH₂Cl₂, EtOAc, and n-BuOH strongly inhibited NO release from RAW264.7 cells. Bioactive mediators derived from CH₂Cl₂ and n-BuOH fractions elicited potent anti-inflammatory actions and strikingly abrogated LPS-triggered NO accumulation in RAW264.7 cells. Of particular interest, capillin and isoscopoletin possessed the most potent NO suppressive effects. Western blot analysis validated the molecular mechanism of NO inhibition and showed that capillin and isoscopoletin significantly down-regulated iNOS and COX-2 protein expression. Taken together, our results provide the first evidence that MeOH extract, CH₂Cl₂, EtOAc, and n-BuOH fractions from A. capillaris and its derived lead candidates can potently suppress inflammatory responses in macrophages by hampering NO release and down-regulating iNOS and COX-2 signaling.


Subject(s)
Artemisia , Blotting, Western , Dermatitis, Atopic , Flavonoids , Inflammation , Macrophages , Obesity
9.
Natural Product Sciences ; : 181-188, 2018.
Article in English | WPRIM | ID: wpr-741620

ABSTRACT

Caryopteris incana (Verbenaceae) has been used to treat cough, arthritis, and eczema in Oriental medicine. The two fractions (CHCl₃- and BuOH fractions) and the essential oil of the plant material were subjected to the inducible nitric oxide synthase (iNOS) assay. The IC₅₀ of the CHCl₃ fraction and the essential oil on LPS-induced macrophage RAW 264.7 cells were 16.4 µg/mL and 23.08 µg/mL, respectively. On gas chromatography (GC)-mass spectroscopy (MS) analysis, twenty-five components representing 85.5% amount of total essential oil were identified. On the chromatogram, three main substances, trans-pinocarveol, cis-citral, and pinocarvone, occupied 18.8%, 13.5% and 18.37% of total peak area. Furthermore, by HPLC-UV analysis, six compounds including one iridoid (8-O-acetylharpagide)- and five phenylethanoid glycosides (caryopteroside, acteoside, phlinoside A, 6-O-caffeoylphlinoside, and leucosceptoside A) isolated from the BuOH fraction were quantified. The content of six compounds were shown as the following order: caryopteroside (162.35 mg/g) > 8-O-acetylharpagide (93.28 mg/g) > 6-O-caffeoylphlinoside (28.15mg/g) > phlinoside (22.60mg/g) > leucosceptoside A (16.87 mg) > acteoside (7.05 mg/g).


Subject(s)
Arthritis , Chromatography, Gas , Chromatography, High Pressure Liquid , Cough , Eczema , Glycosides , Macrophages , Medicine, East Asian Traditional , Nitric Oxide Synthase Type II , Nitric Oxide Synthase , Nitric Oxide , Plants , Spectrum Analysis , Verbenaceae
10.
Natural Product Sciences ; : 13-20, 2018.
Article in English | WPRIM | ID: wpr-741602

ABSTRACT

Estragole is a naturally occurring phenylpropanoid obtained from essential oils found in a broad diversity of plants. Although the phenylpropanoids show many biological activities, clear regulation of the inflammatory signaling pathways has not yet been determined. Here, we scrutinized the anti-inflammatory effect of estragole. The anti-inflammatory effect of estragole was determined through the inhibitory mechanisms of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), nuclear factor kappa B (NF-κB), and mitogen-activated protein kinases (MAPK) pathways and the activation of nuclear factor erythroid 2-related factor 2 (Nrf-2)/heme oxygenase (HO)-1 pathways in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Estragole significantly inhibited NO production, iNOS and COX-2 expression as well as LPS-induced NF-κB and MAPK activation. Furthermore, estragole suppressed LPS-induced intracellular ROS production but up-regulated the stress response gene HO-1 via the activation of transcription factor Nrf-2. These findings demonstrate that estragole inhibits the LPS-induced expression of inflammatory mediators via the down-regulation of iNOS, COX-2, NF-κB, and MAPK pathways, as well as the up-regulation of the Nrf-2/HO-1 pathway, indicating that this phenylpropanoid has potential therapeutic and preventive applications in various inflammatory diseases.


Subject(s)
Down-Regulation , Mitogen-Activated Protein Kinases , NF-kappa B , Nitric Oxide Synthase Type II , Oils, Volatile , Prostaglandin-Endoperoxide Synthases , Transcription Factors , Up-Regulation
11.
Natural Product Sciences ; : 28-35, 2018.
Article in English | WPRIM | ID: wpr-741600

ABSTRACT

Pulegone is a naturally occurring organic compound obtained from essential oils from a variety of plants. The aim of this study was to investigate the anti-inflammatory effects through the inhibitory mechanism of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), nuclear factor kappa B (NF-κB), mitogen-activated protein kinases (MAPK) pathways and the activation of nuclear factor erythroid 2-related factor 2 (Nrf2)/ heme oxygenase (HO)-1 pathways in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Results revealed that pulegone significantly inhibited NO production as well as iNOS and COX-2 expressions. Meanwhile, western blot analysis showed that pulegone down-regulated LPS-induced NF-κB and MAPKs activation in RAW 264.7 cells. Furthermore, the selected compound suppressed LPS-induced intracellular ROS production in RAW 264.7 cells, while the expression of stress response gene, HO-1, and its transcriptional activator, Nrf-2 was upregulated upon pulegone treatment. Taking together, these findings provided that pulegone inhibited the LPS-induced expression of inflammatory mediators via the down-regulation iNOS, COX-2, NF-κB, and MAPKs signaling pathways as well as up-regulation of Nrf-2/HO-1 indicating that pulegone has a potential therapeutic and preventive application in various inflammatory diseases.


Subject(s)
Blotting, Western , Down-Regulation , Heme Oxygenase (Decyclizing) , Mitogen-Activated Protein Kinases , NF-kappa B , Nitric Oxide Synthase Type II , Oils, Volatile , Prostaglandin-Endoperoxide Synthases , Up-Regulation
12.
Asian Pacific Journal of Tropical Biomedicine ; (12): 208-213, 2017.
Article in Chinese | WPRIM | ID: wpr-950618

ABSTRACT

Objective To characterize the types, contents, and peroxynitrite-scavenging activities of flavonoids in the leaf of Carica papaya (C. papaya). Methods Chromatographic and spectroscopic techniques along with high performance liquid chromatography quantitative analysis and peroxynitrite-scavenging assay were performed to isolate and quantify flavonoid compounds in the flavonoid-rich fraction (BuOH fraction) derived from MeOH extract of C. papaya leaves and evaluate their peroxynitrite-scavenging activities. Results Seven flavonoids were isolated from the leaves of C. papaya, including quercetin 3-(2

13.
Asian Pacific Journal of Tropical Biomedicine ; (12): 849-854, 2017.
Article in Chinese | WPRIM | ID: wpr-950505

ABSTRACT

Objective To find the genuine structure with anti-acetylcholinesterase (anti-AChE) from the phenolic glycosides abundant in Leonurus japonicus (Lamiaceae). The assay for anti-AChE activity is often used to lead anti-Alzheimer's drugs. Methods The five phenolic glycosides, tiliroside, leonurusoside C, 2‴-syringoylrutin, rutin, and lavanduliofolioside were isolated from L. japonicus. The activities of the glycosides were relatively low. Seven compounds including p-coumaric acid, caffeic acid, hydroxytyrosol, salidroside, syringic acid, kaempferol, and quercetin, which are produced by the hydrolysis of the five glycosides, were also assayed for anti-AChE activity. Results Of those seven compounds, the five compounds other than salidroside and syringic acid exhibited potent anti-AChE activities. In particular, the IC

14.
Asian Pacific Journal of Tropical Medicine ; (12): 1117-1122, 2017.
Article in Chinese | WPRIM | ID: wpr-972521

ABSTRACT

Objective To discover lead lupane triterpenoid's potential isolated from Pueraria lobata roots against β-site amyloid precursor protein cleaving enzyme 1 (BACE1), which serve as a rate limiting step in amyloid beta (Aβ) production altering the course of Alzheimer's disease. In addition, enzyme kinetics study and molecular docking were conducted to establish the inhibition type and structure activity relationship. Methods A systematic study of 70% ethanolic P. lobata root extract was employed to identify its BACE1 inhibitory potential. Further, BACE1 inhibitory potential of two lupane terpenoids, yielded from ethanolic extract, was assessed. In order to determine their inhibition mode, Lineweaver–Burk plots and Michaelis–Menten model for BACE1 was performed. AutoDock 4.2 program in addition determined the molecular interaction of BACE1 with isolated terpenoids. Results Considering the inhibitory potential of 70% ethanolic extract of P. lobata against BACE1 (IC

16.
Asian Pacific Journal of Tropical Medicine ; (12): 1117-1122, 2017.
Article in English | WPRIM | ID: wpr-819407

ABSTRACT

OBJECTIVE@#To discover lead lupane triterpenoid's potential isolated from Pueraria lobata roots against β-site amyloid precursor protein cleaving enzyme 1 (BACE1), which serve as a rate limiting step in amyloid beta (Aβ) production altering the course of Alzheimer's disease. In addition, enzyme kinetics study and molecular docking were conducted to establish the inhibition type and structure activity relationship.@*METHODS@#A systematic study of 70% ethanolic P. lobata root extract was employed to identify its BACE1 inhibitory potential. Further, BACE1 inhibitory potential of two lupane terpenoids, yielded from ethanolic extract, was assessed. In order to determine their inhibition mode, Lineweaver-Burk plots and Michaelis-Menten model for BACE1 was performed. AutoDock 4.2 program in addition determined the molecular interaction of BACE1 with isolated terpenoids.@*RESULTS@#Considering the inhibitory potential of 70% ethanolic extract of P. lobata against BACE1 (IC = 80.35 μg/mL), lupeol and lupenone were subsequently isolated and exhibited notable or moderate BACE1 inhibitory activity with IC values of 5.12 and 62.98 μmol/L, respectively, as compared to the positive control quercetin (IC = 21.28 μmol/L). The enzyme kinetics study enabled us to identify both compounds as competitive inhibitors, where lupeol displayed a very potent inhibition against BACE1 with low inhibition constant (K) value of 1.43 μmol/L, signifying greater binding affinity. In order to understand the binding mechanism and structure-activity relationship of two triterpene-based BACE1 inhibitors, we employed computer aided docking studies which evidently revealed that hydroxyl group of lupeol formed two hydrogen bonds with the ASP32 (catalytic aspartic residue) and SER35 residues of BACE1 with the binding energy of (-8.2 kcal/mol), while the ketone group of lupenone did not form any hydrogen bonds with BACE1 giving evidence for less binding affinity. These results in turn have predicted the dependence of the inhibitory activity in the presence of hydroxyl group which has provided a new basis for BACE1 blockade.@*CONCLUSIONS@#Our results have successfully explored the molecular mechanism of lupane triterpenoids via BACE1 inhibition, suggesting that lupeol in particular could be utilized as a useful therapeutic and preventive agent to mitigate Alzheimer's disease.

17.
Natural Product Sciences ; : 183-191, 2017.
Article in English | WPRIM | ID: wpr-83907

ABSTRACT

Luteolin 5-O-glucoside is the major flavonoid from Korean thistle, Cirsium maackii. We previously reported the anti-inflammatory activities of luteolin 5-O-glucoside in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. In this study, we determined the anti-inflammatory mechanisms of luteolin 5-O-glucoside through the inhibition of nitric oxide (NO) production in vitro and in vivo. Results revealed that luteolin 5-O-glucoside dose-dependently inhibited NO production and expression of iNOS and COX-2 in LPS-induced RAW 264.7 cells. Luteolin 5-O-glucoside also significantly inhibited the translocation of NF-κB, the activation of MAPKs, and ROS generation in LPS-induced RAW 264.7 cells. In addition, protein expressions of Nrf-2 and HO-1 were also upregulated by luteolin 5-O-glucoside treatment. Moreover, luteolin 5-O-glucoside inhibited λ-carrageenan-induced mouse paw edema by 65.34% and 48.31% at doses of 50 and 100 mg/kg body weight, respectively. These findings indicate potential anti-inflammatory effect of luteolin 5-O-glucoside particularly by downregulating NF-κB and upregulating HO-1/Nrf-2 pathway.


Subject(s)
Animals , Mice , Body Weight , Cirsium , Edema , In Vitro Techniques , Luteolin , Milk Thistle , Milk , Nitric Oxide
18.
Natural Product Sciences ; : 208-212, 2017.
Article in English | WPRIM | ID: wpr-83904

ABSTRACT

A new sesquiterpenoid, 11-hydroxy-valenc-1(10),3(4)-dien-2-one (3), two chemically synthesized but first isolate from nature, 3-oxocedran-8β-ol (1) and valenc-1(10),3(4),11(12)-trien-2-one (2) along with four known compounds, sugiol (4), (+)-nootkatone (5), 11-hydroxy-valenc-1(10)-en-2-one (6), and clovandiol (7), were isolated from the heartwood of Juniperus chinensis. All chemical structures were elucidated using extensive spectroscopic analysis including 1D and 2D NMR spectroscopy. Valenc-1(10),3(4),11(12)-trien-2-one (2) exhibited significant inhibitory activity against butyrylcholinesterase with an IC₅₀ value of 68.45 µM.


Subject(s)
Acetylcholinesterase , Butyrylcholinesterase , Juniperus , Magnetic Resonance Spectroscopy
19.
Asian Pacific Journal of Tropical Medicine ; (12): 103-111, 2016.
Article in Chinese | WPRIM | ID: wpr-951466

ABSTRACT

Objective: To use structure-activity analysis to study the anti-Alzheimer's disease (anti-AD) activity of natural coumarins isolated from Angelica decursiva and Artemisia capillaris, along with one purchased coumarin (daphnetin). Methods: Umbelliferone, umbelliferone 6-carboxylic acid, scopoletin, isoscopoletin, 7-methoxy coumarin, scoparone, scopolin, and esculetin have been previously isolated; however 2'-isopropyl psoralene was isolated from Angelica decursiva for the first time to evaluate their inhibitory effects against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) enzyme activity. We scrutinized the potentials of coumarins as cholinesterase and BACE1 inhibitors via enzyme kinetics and molecular docking simulation. Results: Among the test compounds, umbelliferone 6-carboxylic acid, esculetin and daphnetin exhibited potent inhibitory activity against AChE, BChE and BACE1. Both esculetin and daphnetin have a catechol group and exhibit significant anti-AD activity against AChE and BChE. In contrast, presence of a sugar moiety and methoxylation markedly reduced the anti-AD activity of the coumarins investigated in this study. With respect to BACE1 inhibition, umbelliferone 6-carboxylic acid, esculetin and daphnetin contained carboxyl or catechol groups, which significantly contributed to their anti-AD activities. To further investigate these results, we generated a 3D structure of BACE1 using Autodock 4.2 and simulated binding of umbelliferone 6-carboxylic acid, esculetin and daphnetin. Docking simulations showed that different residues of BACE1 interacted with hydroxyl and carboxylic groups, and the binding energies of umbelliferone 6-carboxylic acid, esculetin and daphnetin were negative (-4.58, -6.25 and -6.37 kcal/mol respectively). Conclusions: Taken together, our results suggest that umbelliferone 6-carboxylic acid, esculetin and daphnetin have anti-AD effects by inhibiting AChE, BChE and BACE1, which might be useful against AD.

20.
Biomolecules & Therapeutics ; : 650-658, 2016.
Article in English | WPRIM | ID: wpr-209967

ABSTRACT

Chronic alcohol consumption causes alcoholic liver disease, which is associated with the initiation of dysregulated lipid metabolism. Recent evidences suggest that dysregulated cholesterol metabolism plays an important role in the pathogenesis of alcoholic fatty liver disease. Ecklonia stolonifera (ES), a perennial brown marine alga that belongs to the family Laminariaceae, is rich in phlorotannins. Many studies have indicated that ES has extensive pharmacological effects, such as antioxidative, hepatoprotective, and antiinflammatory effects. However, only a few studies have investigated the protective effect of ES in alcoholic fatty liver. Male Sprague-Dawley rats were randomly divided into normal diet (ND) (fed a normal diet for 10 weeks) and ethanol diet (ED) groups. Rats in the ED group were fed a Lieber-DeCarli liquid diet (containing 5% ethanol) for 10 weeks and administered ES extract (50, 100, or 200 mg/kg/day), silymarin (100 mg/kg/day), or no treatment for 4 weeks. Each treatment group comprised of eight rats. The supplementation with ES resulted in decreased serum levels of triglycerides (TGs), total cholesterol, alanine aminotransferase, and aspartate aminotransferase. In addition, there were decreases in hepatic lipid and malondialdehyde levels. Changes in liver histology, as analyzed by Oil Red O staining, showed that the ES treatment suppressed adipogenesis. In addition, the ES treatment increased the expression of fatty acid oxidation-related genes (e.g., PPAR-α and CPT-1) but decreased the expression of SREBP 1, which is a TG synthesis-related gene. These results suggest that ES extract may be useful in preventing fatty acid oxidation and reducing lipogenesis in ethanol-induced fatty liver.


Subject(s)
Animals , Humans , Male , Rats , Adipogenesis , Alanine Transaminase , Alcohol Drinking , Aspartate Aminotransferases , Cholesterol , Diet , Ethanol , Fatty Liver , Fatty Liver, Alcoholic , Lipid Metabolism , Lipogenesis , Liver , Liver Diseases, Alcoholic , Malondialdehyde , Metabolism , Rats, Sprague-Dawley , Silymarin , Triglycerides
SELECTION OF CITATIONS
SEARCH DETAIL