Cholinesterase inhibitory triterpenoids from the bark of Garcinia hombroniana (original) (raw)
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Cholinesterase inhibitory triterpenoids from the bark ofGarcinia hombroniana
Journal of Enzyme Inhibition and Medicinal Chemistry, 2014
Context: Garcinia hombroniana Pierre, known as manggis hutan in Malaysia is a rich source of xanthones and benzophenones. Objectives: This study was aimed to isolate and characterize potential cholinesterase inhibitors from the extracts of G. hombroniana bark and investigate their interactions with the enzymes. Materials and methods: The dichloromethane extract afforded five triterpenoids which were characterized by NMR and mass spectral techniques. Cholinesterase inhibitory assay and molecular docking were performed to get insight of the inhibitory activity and molecular interactions of the compounds. The compounds were also tested for their antioxidant capacity. Results: The isolated triterpenoids were identified as: 2-hydroxy-3-O-caffeoyltaraxar-14-en-28oic acid (1), taraxerol (2), taraxerone (3), betulin (4) and betulinic acid (5). Compound 1 was the most active dual inhibitor of both AChE and BChE. Compound 1 also showed good antioxidant activities. Conclusion: Compound 1 had dual and moderate inhibitory activity on AChE and BChE worthy for further investigations.
Fitoterapia, 2020
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Chemico-Biological Interactions, 2009
Flavonoids are one of the largest classes of plant secondary metabolites and are known to possess a number of significant biological activities for human health. In this study, we examined in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of four flavonoid derivatives -quercetin, rutin, kaempferol 3-O--d-galactoside and macluraxanthone. The in vitro results showed that quercetin and macluraxanthone displayed a concentration-dependant inhibition of AChE and BChE. Macluraxanthone showed to be the most potent and specific inhibitor of both the enzymes having the IC 50 values of 8.47 and 29.8 M, respectively. The enzyme kinetic studies revealed that quercetin inhibited both the enzymes in competitive manner, whereas the mode of inhibition of macluraxanthone was noncompetitive against AChE and competitive against BChE. The inhibitory profiles of the compounds have been compared with standard AChE inhibitor galanthamine. To get insight of the intermolecular interactions, the molecular docking studies of these two compounds were performed at the active site 3D space of both the enzymes, using ICM-Dock TM module. Docking studies exhibited that macluraxanthone binds much more tightly with both the enzymes than quercetin. The calculated docking and binding energies also supported the in vitro inhibitory profiles (IC 50 values). Both the compounds showed several strong hydrogen bonds to several important amino acid residues of both the enzymes. A number of hydrophobic interactions could also explain the potency of the compounds to inhibit AChE and BChE.
New Cholinesterase-Inhibiting Triterpenoid Alkaloids fromBuxus hyrcana
Chemistry & Biodiversity, 2006
The current phytochemical investigation on Buxus hyrcana Pojark. has resulted in the isolation of the triterpenoid alkaloids 1 -10. The structures of five new alkaloids, hyrcanone (1), hyrcanol (2), hyrcatrienine (3), N b -dimethylcycloxobuxoviricine (4), and hyrcamine (5), were elucidated by means of modern spectroscopic techniques, while the known alkaloids, buxidin , buxandrine , buxabenzacinine (8), buxippine-K (9) and E-buxenone (10), were identified by comparing their spectral data with those reported earlier. Compounds 1 and 3 -9 were found to be acetyl-and butyrylcholinesterase inhibitors. The IC 50 values were estimated to be in the range of 83.0 -468.0 mm against AChE and 1.12 -350.0 mm against BChE. The structure -activity relationship studies suggested that the presence of dimethylamino moieties at C(3) and C(20) is the most important factor influencing the activity of these compounds against the cholinesterase enzymes. All compounds were also evaluated for cytotoxicity on a fibroblast cell line with incubation of 24 h. No cytotoxic effects were exerted by any compound.
Food Chemistry, 2012
The present study aimed to evaluate acetylcholinesterase (AChE) inhibitory and antioxidant activities of Lamiaceae medicinal plants growing wild in Croatia. Using Ellman's colorimetric assay all tested ethanolic extracts and their hydroxycinnamic acid constituents demonstrated in vitro AChE inhibitory properties in a dose dependent manner. The extracts of Mentha x piperita, M. longifolia, Salvia officinalis, Satureja montana, Teucrium arduini, T. chamaedrys, T. montanum, T. polium and Thymus vulgaris at 1 mg/mL showed strong inhibitory activity against AChE. The antioxidant potential of the investigated Lamiaceae species was assessed by DPPH • scavenging activity and total antioxidant capacity assays, in comparison with hydroxycinnamic acids and trolox. The extracts differed greatly in their total hydroxycinnamic derivatives content, determined spectrophotometrically. Rosmarinic acid was found to be the predominant constituent in most of the investigated medicinal plants (by RP-HPLC) and had a substantial influence on their AChE inhibitory and antioxidant properties, with the exception of Teucrium species. These findings indicate that Lamiaceae species are a rich source of various natural AChE
Molecules, 2013
Plants of the Apocynaceae family have been traditionally used in the treatment of age-related brain disorders. Rauvolfia reflexa, a member of the family, has been used as an antidote for poisons and to treat malaria. The dichloromethane, ethanol and methanol extracts from the leaves of Rauvolfia reflexa showed potential acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, with IC 50 values in the 8.49 to 52.23 g/mL range. Further cholinesterase inhibitory-guided isolation of these extracts afforded four bioactive compounds, namely: (E)-3-(3,4,5-trimethoxyphenyl)acrylic acid (1), (E)-methyl 3-(4-hydroxy-3,5-dimethoxyphenyl) acrylate (2), 17-methoxycarbonyl-14-heptadecaenyl-4hydroxy-3-methoxycinnamate (3) and 1,2,3,4-tetrahydro-1-oxo-β-carboline (4). The isolated compounds showed moderate cholinesterase inhibitory activity compared to the reference standard, physostigmine. Compounds 1 and 2 showed the highest inhibitory activity against AChE (IC 50 = 60.17 µM) and BChE (IC 50 = 61.72 µM), respectively. Despite having similar molecular weight, compounds 1 and 2 were structurally different according to their chemical substitution patterns, leading to their different enzyme inhibition selectivity. Compound 2 was more selective against BChE, whereas compound 1 was a selective inhibitor of AChE. Molecular docking revealed that both compounds 1 and 2 were inserted, but not deeply into the active site of the cholinesterase enzymes.
Food and Chemical Toxicology, 2013
Extracts, fractions and compounds from Calceolaria talcana and C. integrifolia exhibited strong inhibitory effects of the activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes using the in vitro Ellmańs method. The most active samples were from the ethyl acetate extract, which caused a mixed-type inhibition against AChE (69.8% and 79.5% at 100 and 200 μg/ml, respectively) and against BChE (98.5% and 99.8% at 100 and 200 μg/ml, respectively) and its major components verbascoside 8 (50.9 and 70.0% at 200 μg/ml, against AChE and BChE, respectively), martynoside 9, and fraction F-7 (which corresponds to a mixture of 8, 9, and other phenylethanoids and phenolics that remain unidentified) (80.2 and 85.3% at 100 and 200 μg/ml, against AChE, respectively and 99.1 and 99.7% at 100 and 200 μg/ml, against BChE, respectively) inhibited the acetylcholinesterase enzyme competitively. The most polar fraction F-5 from n-hexane extract (a mixture of naphthoquinones: 2-hydroxy-3-(1,1-dimethylallyl-1,4-naphthoquinone) 6, α-dunnione 7 and other polar compounds that remain unidentified) showed a mixed-type inhibition (71.5 and 72.1% against AChE and BChE at 200 μg/ml, respectively). Finally, the methanol-soluble residue presented a complex, mixed-type inhibition (39.9 and 67.9% against AChE and BChE at 200 μg/ml, respectively). The mixture F-3 with diterpenes was obtained from the n-hexane extract: (1,10-cyclopropyl-9-epi-ent-isopimarol) 1, 19-α-hydroxy-abietatriene 2, and F-4 a mixture of triterpenes α-lupeol 3, β-sitosterol 4, ursolic acid 5 together with a complex mixture of terpenes that did not show activity. In summary, extracts and natural compounds from C. talcana and C. integrifolia were isolated, identified and characterized as cholinesterase inhibitors.
Evaluation of Antioxidant and Cholinesterase Inhibitory Activities of Some Medicinal Plants
Food and Health, 2019
The aim of this study was to determine total phenolic and total flavonoid contents, antioxidant and anticholinesterase activities of the hexane, acetone and ethanol extracts prepared from mantle, rosemary, thistle, mallow and nettle commonly consumed for medicinal and nutraceutical purposes in Turkey and all around the world. DPPH free radical, ABTS cation radical and superoxide anion radical scavenging assays, and Ellman method were used to establish the antioxidant and anticholinesterase potential of the extracts, respectively. Total phenolic and total flavonoid contents of the mantle ethanol extract were found to be the richest extract among the others. Mantle ethanol and thistle hexane extracts in DPPH free radical scavenging method (88.03% and 88.07%, respectively), and acetone and ethanol extracts of mantle and rosemary in ABTS cation radical scavenging assay showed the highest inhibition (88.60% and 89.73%, respectively) at 100 μg/mL concentration. None of the extracts exhibited superoxide anion radical scavenging activity. Nettle ethanol extract indicated higher butyrylcholinesterase inhibitory activity (92.68%) than galanthamine, mallow acetone extract as galanthamine, mantle hexane, mallow hexane and ethanol, and nettle acetone extracts almost as galanthamine. To our knowledge, ABTS cation radical and superoxide anion radical scavenging activities, and anticholinesterase potential of the extracts prepared from mantle leaves and flowers, anticholinesterase effect of thistle seeds extracts, ABTS cation radical scavenging activity and butyrylcholinesterase inhibitory activity of the extracts prepared from mallow leaves and flowers were investigated for the first time in this study.
Cholinesterase inhibitors from botanicals
Pharmacognosy Reviews, 2013
Alzheimer's disease (AD) is a progressive neurodegenerative disease, wherein a progressive loss of cholinergic synapses occurs in hippocampus and neocortex. Decreased concentration of the neurotransmitter, acetylcholine (ACh), appears to be critical element in the development of dementia, and the most appropriate therapeutic approach to treat AD and other form of dementia is to restore acetylcholine levels by inhibiting both major form of cholinesterase: Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Consequently, researches have focused their attention towards finding cholinesterase inhibitors from natural products. A large number of such inhibitors have been isolated from medicinal plants. This review presents a comprehensive account of the advances in field of cholinesterase inhibitor phytoconstituents. The structures of some important phytoconstituents (collected through www.Chemspider.com) are also presented and the scope for future research is discussed.