Title: Efficient Synthesis of Stearidonic Acid Enriched Triacylglycerol from Ahiflower Seed Oil via a Two-Step Enzyme Reaction Ju C, Lee YJ, Yoon HS, Kim BH, Kim IH Ref: J Oleo Sci, 71:1679, 2022 : PubMed
Stearidonic acid (SDA) is a plant-based n-3 polyunsaturated fatty acid with multiple biological activities. The enrichment of SDA and synthesis of triacylglycerol (TAG) were carried out consecutively via two lipase-catalyzed reactions, hydrolysis, and esterification. First, SDA was enriched into a glyceride fraction from ahiflower seed oil by Candida rugosa lipase-catalyzed hydrolysis. Under the optimum conditions of 35 degreesC, 0.1% lipase powder of Lipase OF, and 50% buffer solution (based on the weight of total substrate), SDA was enriched from 21.6 to 40.7 wt% in glyceride fraction. SDA-enriched TAG was then synthesized from the SDA-enriched glyceride and the SDA-enriched fatty acid via esterification using an in-house immobilized lipase as a biocatalyst. The SDA-enriched fatty acid was obtained from part of the SDA-enriched glyceride by saponification and the in-house immobilized lipase was prepared from Eversa((a)) Transform 2.0 using Lewatit VP OC 1600 as a carrier. The optimum reaction conditions for the synthesis of TAG were a temperature of 50 degreesC, an enzyme loading of 10%, and a vacuum of 10 mmHg. A maximum conversion to TAG of ca. 94% was achieved after 12 h under the optimum conditions.
Title: Inhibition of soluble epoxide hydrolase by phytochemical constituents of the root bark of Ulmus davidiana var. japonica Kim JH, Park JS, Lee YJ, Choi S, Kim YH, Yang SY Ref: J Enzyme Inhib Med Chem, 36:1049, 2021 : PubMed
A novel compound 1 and nine known compounds (2-10) were isolated by open column chromatography analysis of the root bark of Ulmus davidiana. Pure compounds (1-10) were tested in vitro to determine the inhibitory activity of the catalytic reaction of soluble epoxide hydrolase (sEH). Compounds 1, 2, 4, 6-8, and 10 had IC(50) values ranging from 11.4 +/- 2.3 to 36.9 +/- 2.6 microM. We used molecular docking to simulate inhibitor binding of each compound and estimated the binding pose of the catalytic site of sEH. From this analysis, the compound 2 was revealed to be a potential inhibitor of sEH in vitro and in silico. Additionally, molecular dynamics (MD) study was performed to find detailed interaction signals of inhibitor 2 with enzyme. Finally, compound 2 is promising candidates for the development of a new sEH inhibitor from natural plants.
Breast cancer progression results from subversion of multiple intra- or intercellular signaling pathways in normal mammary tissues and their microenvironment, which have an impact on cell differentiation, proliferation, migration, and angiogenesis. Phospholipases (PLC, PLD and PLA) are essential mediators of intra- and intercellular signaling. They hydrolyze phospholipids, which are major components of cell membrane that can generate many bioactive lipid mediators, such as diacylglycerol, phosphatidic acid, lysophosphatidic acid, and arachidonic acid. Enzymatic processing of phospholipids by phospholipases converts these molecules into lipid mediators that regulate multiple cellular processes, which in turn can promote breast cancer progression. Thus, dysregulation of phospholipases contributes to a number of human diseases, including cancer. This review describes how phospholipases regulate multiple cancer-associated cellular processes, and the interplay among different phospholipases in breast cancer. A thorough understanding of the breast cancer-associated signaling networks of phospholipases is necessary to determine whether these enzymes are potential targets for innovative therapeutic strategies.
Title: Neuroprotective Effect of Cudrania tricuspidata Fruit Extracts on Scopolamine-Induced Learning and Memory Impairment Jee SC, Lee KM, Kim M, Lee YJ, Kim S, Park JO, Sung JS Ref: Int J Mol Sci, 21:, 2020 : PubMed
Cudrania tricuspidata has diverse biological activities, such as antioxidant, anti-inflammatory, anticancer, and neuroprotective effects. This study investigated the protective effects of C. tricuspidata fruit extracts (CTFE) against scopolamine (SCO)-induced neuron impairment. The neuroprotective effects of CTFE on SCO-induced memory dysfunction were confirmed in mice using the Barnes maze test. The results showed that co-treatment of SCO and CTFE increased the stay time in the target zone compared with SCO treatment alone. Similarly, the results obtained by the fear conditioning test revealed that SCO-CTFE co-treatment induced the freezing action time under both the contextual fear condition and the cued fear condition compared with SCO treatment alone. Moreover, we showed that CTFE reduced the SCO-induced acetylcholinesterase (AChE) activity, thereby increasing the acetylcholine concentration in mice hippocampal tissues. Consistent with the improvement of memory and recognition function in vivo, our in vitro results showed that CTFE induced cAMP response element binding protein (CREB) and extracellular regulated kinase 1/2 (ERK1/2) activity in PC12 cells and reduced SCO-induced AChE activity. In addition, the microarray results of the hippocampal tissue support our data showing that CTFE affects gene expressions associated with neurogenesis and neuronal cell differentiation markers such as spp1 and klk6. Overall, CTFE exerts a neuroprotective effect via regulation of the CREB and ERK1/2 signaling pathways and could be a therapeutic candidate for neurodegenerative diseases.
Title: Functional expression of polyethylene terephthalate-degrading enzyme (PETase) in green microalgae Kim JW, Park SB, Tran QG, Cho DH, Choi DY, Lee YJ, Kim HS Ref: Microb Cell Fact, 19:97, 2020 : PubMed
BACKGROUND: For decades, plastic has been a valuable global product due to its convenience and low price. For example, polyethylene terephthalate (PET) was one of the most popular materials for disposable bottles due to its beneficial properties, namely impact resistance, high clarity, and light weight. Increasing demand of plastic resulted in indiscriminate disposal by consumers, causing severe accumulation of plastic wastes. Because of this, scientists have made great efforts to find a way to biologically treat plastic wastes. As a result, a novel plastic degradation enzyme, PETase, which can hydrolyze PET, was discovered in Ideonella sakaiensis 201-F6 in 2016. RESULTS: A green algae, Chlamydomonas reinhardtii, which produces PETase, was developed for this study. Two representative strains (C. reinhardtii CC-124 and CC-503) were examined, and we found that CC-124 could express PETase well. To verify the catalytic activity of PETase produced by C. reinhardtii, cell lysate of the transformant and PET samples were co-incubated at 30 degC for up to 4 weeks. After incubation, terephthalic acid (TPA), i.e. the fully-degraded form of PET, was detected by high performance liquid chromatography analysis. Additionally, morphological changes, such as holes and dents on the surface of PET film, were observed using scanning electron microscopy. CONCLUSIONS: A PET hydrolyzing enzyme, PETase, was successfully expressed in C. reinhardtii, and its catalytic activity was demonstrated. To the best of our knowledge, this is the first case of PETase expression in green algae.
In the present study, we examined whether glutathione peroxidase-1 (GPx-1), a major H(2)O(2) scavenger in the brain, affects memory deficits induced by Abeta (1-42) in mice. Treatment with 400 pmol/5 l Abeta (1-42) (i.c.v.) resulted in a reduction of GPx-1 expression in wild type (WT) mice. An Abeta (1-42)-induced reduction in acetylcholine (ACh) level was observed in the hippocampus. Treatment with Abeta (1-42) consistently resulted in reduced expression and activity of choline acetyltransferase (ChAT) and in an increase in expression and activity of acetylcholinesterase (AChE). Upon examining each of the muscarinic acetylcholine receptors (mAChRs) and nicotinic AChRs, we noted that Abeta (1-42) treatment selectively reduced the levels of M1 mAChR. In addition, Abeta (1-42) induced a significant reduction in phospho-cAMP response element-binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) expression. The cholinergic impairments induced by Abeta (1-42) were more pronounced in GPx-1 knockout mice than in WT mice. Importantly, an adenoviral vector encoded with the GPx-1 gene (Ad-GPx-1) significantly rescued Abeta (1-42)-induced cholinergic impairments in GPx-1 knockout mice. In addition, M1 mAChR antagonist dicyclomine significantly counteracted Ad-GPx-1-mediated increases in p-CREB and BDNF expression, as well as memory-enhancing effects in GPx-1 knockout mice, thus indicating that M1 mAChR might be a critical mediator for the rescue effects of Ad-GPx-1. Combined, our results suggest that GPx-1 gene protected against Abeta (1-42)-induced memory impairments via activation of M1 mAChR-dependent CREB/BDNF signaling.
Title: Design, synthesis and biological evaluation of water-soluble phenytoin prodrugs considering the substrate recognition ability of human carboxylesterase 1 Takahashi M, Lee YJ, Kanayama T, Kondo Y, Nishio K, Mukai K, Haba M, Hosokawa M Ref: Eur J Pharm Sci, :105455, 2020 : PubMed
Human carboxylesterase 1 (hCES1) is a hydrolase that is mainly expressed in the liver and lung and plays the most important role in the metabolic activation of ester-type prodrugs. In this study, design, synthesis and evaluation of water-soluble phenytoin prodrugs were performed with consideration of the substrate recognition ability of hCES1. The phenytoin prodrugs were synthesized in two steps without column chromatography. It was confirmed that all prodrugs are efficiently converted to phenytoin in a human liver microsome (HLM) solution (up to 54.6 nmol/mg protein/min). Although some of the prodrugs were degraded in strongly basic solution, the solubility of all prodrugs was greater than that of phenytoin in buffer solutions at pH 7.4 and 8.3. Among the synthesized phenytoin prodrugs, the 3,3-dimethylglutarate prodrug was superior in terms of solubility and stability, and it showed solubility of 10 mg/mL or more (phenytoin: <0.1 mg/mL) in a solution of pH 8.3. It was also found that the 3,3-dimethylglutarate prodrug was selectively activated by hCES1 but not hCES2 or arylacetamidodeacetylase.
Wild ginseng is known to contain additional physiologically and pharmacologically active substances than common ginseng. The utilization of this herb can be maximized by altering its composition via tissue culture generating adventitious roots. We enriched the content of specific ginsenosides and investigated their role in ameliorating memory impairment. Cultured wild ginseng root was subjected to extraction, steaming, and fermentation using Pediococcus pentosaceus HLJG0702 to enhance the levels of ginsenosides Rg5 /Rk1. The analysis of product, HLJG0701, confirmed target ginsenosides. We analyzed the inhibitory effect of ginsenoside Rg5/Rk1, HLJG0701 and the raw material on acetylcholinesterase. Further, we performed Morris water maze, Y-maze, and passive avoidance tasks with mice exhibiting memory deficit induced by scopolamine, and we analyzed the concentrations of acetylcholinesterase and acetylcholine in their brains. Studies showed that the levels of ginsenosides Rg5 /Rk1, not found in the raw material, were enhanced in HLJG0701. Ginsenosides and HLJG0701 significantly inhibited acetylcholinesterase unlike the raw material. In all behavioral tasks, HLJG0701 showed memory improvement. It reduced acetylcholinesterase, whereas, it preserved acetylcholine in brain. In conclusion, cultured wild ginseng root extract fermented by P. pentosaceus HLJG0702 contains the distinctive ginsenosides Rg5/Rk1, which may ameliorate memory impairment via inhibition of acetylcholinesterase resulting in increased acetylcholine levels in the brain.
Researches on spicatoside A (SpiA)-containing natural products suggest the possibility of SpiA as a potential laxative to alleviate chronic constipation. However, no studies have been conducted with single compound administration of SpiA. To verify the laxative effects and mechanism of action of SpiA on chronic constipation, we investigated alterations in the excretion parameters, histological structure, and cholinergic regulation of the enteric nerve in the colons of Institute of Cancer Research (ICR) mice with loperamide (Lop)-induced constipation after exposure to 20 mg/kg of SpiA. Decrease in the number, weight and water contents of stools in the Lop+Vehicle treated group significantly recovered after SpiA treatment, and alterations in the histological structure and transmission electron microscopy (TEM) images were improved in the Lop+SpiA treated group. Similar recovery effects were observed in the ability for mucin secretion and expression of the membrane water channel gene (aquaporin 8, AQP8). Furthermore, significant improvements were observed in the acetylcholinesterase (AChE) activity and acetylcholine receptors' (AChRs) downstream signaling pathway after treatment of SpiA. The levels of gastrointestinal (GI) hormones including cholecystokinin (CCK) and gastrin were also remarkably enhanced in the Lop+SpiA treated group as compared to the Lop+Vehicle treated group. The expression of receptor tyrosine kinase (C-kit) and protein gene product 9.5 (PGP9.5) in Cajal and neural cells, as well as the phosphorylation of myosin light chain (MLC) in smooth muscle cells, were recovered after SpiA exposure. Taken together, the results of the present study provide the first strong evidence that SpiA improves chronic constipation through muscarinic cholinergic regulation of the enteric nerve in a Lop-induced constipation ICR mice model.
Title: In silico approaches to evaluate the molecular properties of organophosphate compounds to inhibit Acetylcholinesterase activity in housefly Marimuthu P, Lee YJ, Kim BH, Seo SS Ref: J Biomol Struct Dyn, :1, 2018 : PubMed
Organophosphate compounds (OPC) have become the primary choice as insecticides and is widely used across the world. Additionally, OPCs were also commonly used as a chemical warfare agent that triggers a great challenge to public safety. Exposure of OPCs to human causes immediate excitation of cholinergic neurotransmission through transient elevation of synaptic acetylcholine (ACh) levels and accumulations. Likewise, prolonged exposure of OPCs can affect the processes in immune response, carbohydrate metabolism, cardiovascular toxicity and several others. Studies revealed that, toxicity of OPCs was provoked by inhibition of acetylcholinesterase (AChE). Therefore, combined in silico approaches -pharmacophore-based 3D-QSAR model; docking and Molecular Dynamics (MD)- were used to assess the precise and comprehensive effects of series of known OP derived compounds together with its -log LD50 values. The selected five-featured pharmacophore model -AAHHR.61- displayed the highest correlation (R(2)=0.9166), cross-validated coefficient (Q(2)=0.8221), F=63.2, Pearson-R=0.9615 with low RMSE=0.2621 values obtained using five component PLS factor. Subsequently, the well-validated model was then used as a 3D query to search novel OPCs using high-throughput virtual screening technique. Simultaneously, the docking studies predicted the binding pose of most active OPC in the MdAChE binding pocket. Additionally, the stability of docking was verified using MD simulation. The results revealed that OP22 and predicted lead compounds binds tightly to S315 of MdAChE through potential hydrogen bond interaction over the time. Overall, this study might provide valuable insight on binding mode of OPCs and hit compounds to inhibit AChE in housefly.
Cognitive impairment responses are important research topics in the study of degenerative brain diseases as well as in understanding of human mental activities. To compare response to scopolamine (SPL)-induced cognitive impairment, we measured altered parameters for learning and memory ability, inflammatory response, oxidative stress, cholinergic dysfunction and neuronal cell damages, in Korl:ICR stock and two commercial breeder stocks (A:ICR and B:ICR) after relevant SPL exposure. In the water maze test, Korl:ICR showed no significant difference in SPL-induced learning and memory impairment compared to the two different ICRs, although escape latency was increased after SPL exposure. Although behavioral assessment using the manual avoidance test revealed reduced latency in all ICR mice after SPL treatment as compared to Vehicle, no differences were observed between the three ICR stocks. To determine cholinergic dysfunction induction by SPL exposure, activity of acetylcholinesterase (AChE) assessed in the three ICR stocks revealed no difference of acetylcholinesterase activity. Furthermore, low levels of superoxide dismutase (SOD) activity and high levels of inflammatory cytokines in SPL-treated group were maintained in all three ICR stocks, although some variations were observed between the SPLtreated groups. Neuronal cell damages induced by SPL showed similar response in all three ICR stocks, as assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, Nissl staining analysis and expression analyses of apoptosis-related proteins. Thus, the results of this study provide strong evidence that Korl:ICR is similar to the other two ICR. Stocks in response to learning and memory capacity.
Title: Neuroprotective effects of Danggui-Jakyak-San on rat stroke model through antioxidant/antiapoptotic pathway Kim SH, Chung DK, Lee YJ, Song CH, Ku SK Ref: J Ethnopharmacol, 188:123, 2016 : PubMed
ETHNOPHARMACOLOGICAL RELEVANCE: Dangui-Jakyak-San (DJ) is a traditional Korean medicinal polyherb, prescribed typically in patients with insufficient blood supply in Eastern Asia. The DJ also has been reported to have neuroprotective effects in vitro and in vivo studies. AIM OF STUDY: The therapeutic potential of DJ was examined in stroke rat model, in comparison with donepezil, a reversible acetylcholinesterase inhibitor. MATERIALS AND METHODS: Ischemic stroke rat model was induced by surgery of permanent occlusion of middle cerebral artery (pMCAO). The model was orally administered with distilled water (pMCAO control), donepezil at 10mg/kg (Donepezil) and DJ at 200, 100 and 50mg/kg (DJ 200, DJ 100 and DJ 50, respectively). Sham had the same surgery excepting for the pMCAO, and it was administered with distilled water (sham control). RESULTS: After the administration for 28 days, the groups of DJ exhibited dose-dependent reduction in infarct/defect volumes with improvement in sensorimotor and cognitive motor function, comparing to pMCAO control. The DJ treatments seemed to enhance antiapoptotic and antioxidant effects; increases in antiapoptotic expressions (STAT3 and Pim-1) and decreases in lipid peroxidation (MDA) together with increases in contents of endogenous antioxidant (GSH) and activities of antioxidant enzymes (catalase and SOD). The histopathological analyses revealed significant reduction in neuronal apoptosis (caspase-3 and PARP) and neuronal degradation with atrophy and degeneration, in the DJ treatments. Furthermore, the oxidative stresses (nitrotyrosine as an iNOS factor and 4-HNE as a marker of lipid peroxidation) were observed mild. Although the similar neuroprotective effects were observed, the body weight loss was scarcely alleviated in Donepezil comparing to pMCAO control. CONCLUSION: These suggest that DJ ameliorate the neurological dysfunction of cerebral ischemia through augmentation of antioxidant defense system and up-regulation of STAT3 and Pim-1.
Title: Rescuing cholinergic neurons from apoptotic degeneration by targeting of serotonin modulator-and apolipoprotein E-conjugated liposomes to the hippocampus Kuo YC, Lee YJ Ref: Int J Nanomedicine, 11:6809, 2016 : PubMed
beta-Amyloid (Abeta)-targeting liposomes (LIP) with surface serotonin modulator (SM) and apolipoprotein E (ApoE) were utilized to facilitate the delivery of nerve growth factor (NGF) across the blood-brain barrier (BBB) for neuroprotection in the hippocampus. The therapeutic efficacy of SM- and ApoE-grafted LIP carrying NGF (NGF-SM-ApoE-LIP) was assessed by an in vitro Alzheimer's disease (AD) model of degenerated SK-N-MC cells and an in vivo AD model of Abeta-insulted Wistar rats. The experimental evidences revealed that the modified SM and ApoE on the surface of LIP increased the permeation of NGF across the BBB without serious damage to structural integrity of tight junction. When compared with free NGF, NGF-SM-ApoE-LIP upregulated the expression of phosphorylated neurotrophic tyrosine kinase receptor type 1 on cholinergic neurons and significantly improved their survival. In addition, NGF-SM-ApoE-LIP could reduce the secretion of acetylcholinesterase and malondialdehyde and rescue hippocampal neurons from apoptosis in rat brains. The synergistic effect of SM and ApoE is promising in the induction of NGF to inhibit the neurotoxicity of Abeta and NGF-SM-ApoE-LIP can be a potent antiapoptotic pharmacotherapy for clinical care of patients with AD.
Title: Sulforaphane induced adipolysis via hormone sensitive lipase activation, regulated by AMPK signaling pathway Lee JH, Moon MH, Jeong JK, Park YG, Lee YJ, Seol JW, Park SY Ref: Biochemical & Biophysical Research Communications, 426:492, 2012 : PubMed
Sulforaphane, an aliphatic isothiocyanate derived from cruciferous vegetables, is known for its antidiabetic properties. The effects of sulforaphane on lipid metabolism in adipocytes are not clearly understood. Here, we investigated whether sulforaphane stimulates lipolysis. Mature adipocytes were incubated with sulforaphane for 24h and analyzed using a lipolysis assay which quantified glycerol released into the medium. We investigated gene expression of hormone-sensitive lipase (HSL), and levels of HSL phosphorylation and AMP-activated protein kinase on sulforaphane-mediated lipolysis in adipocytes. Sulforaphane promoted lipolysis and increased both HSL gene expression and HSL activation. Sulforaphane suppressed AMPK phosphorylation at Thr-172 in a dose-dependent manner, which was associated with a decrease in HSL phosphorylation at Ser-565, enhancing the phosphorylation of HSL Ser-563. Taken together, these results suggest that sulforaphane promotes lipolysis via hormone sensitive lipase activation mediated by decreasing AMPK signal activation in adipocytes.
Title: Does Alzheimer's Disease Protect against Cancers? A Nationwide Population-Based Study Ou SM, Lee YJ, Hu YW, Liu CJ, Chen TJ, Fuh JL, Wang SJ Ref: Neuroepidemiology, 40:42, 2012 : PubMed
Background Previous studies suggested a decreased risk of cancer among patients with Alzheimer's disease AD There is still a lack of data on the specific types of cancer the risk factors and the impact of cholinesterase inhibitors on developing cancer in AD Methods We performed a nationwide population-based study of 6,960 patients with AD between 1997 and 2006 using Taiwan's National Health Insurance database Patterns of cancer incidence in AD patients were compared with those of the general population using standardized incidence ratios SIRs Results Patients with AD had a reduced risk of developing overall cancer SIR 0.88 95 confidence interval CI 0.80-0.97 Specifically patients with AD were protected from lung cancers SIR 0.75 95 CI 0.57-0.98 especially men SIR 0.61 95 CI 0.40-0.88 In subgroup analyses women patients aged 60-79 years and those diagnosed as having AD for more than 1 year were more likely to be protected from cancers Conclusions Our study demonstrates a decreased incidence of overall cancers in patients with AD a finding lower than but consistent with Western countries Patients with AD had a significantly decreased risk of lung cancer Further investigation of genetic evidence linking AD to cancer is warranted.
Autosomal-recessive woolly hair (ARWH)/hypotrichosis is a hereditary hair disorder which is characterized by tightly curled hair and is associated with sparse hair. ARWH can be caused by mutations in the P2RY5 or lipase H (LIPH) gene. Disruption of either gene results in phenotypes with features of both wooly hair (WH) and hypotrichosis. In this study, we identified two Guyanese families with ARWH. Both families are of recent Indian descent. Mutation analysis resulted in the identification of mutations in the LIPH gene in both families. Affected individuals in the first family carry compound heterozygous mutations Ex7_8del and 1303_1309dupGAAAACG in the LIPH gene, while those in the second family have a homozygous mutation 659_660delTA in the LIPH gene. The mutations Ex7_8del and 659_660delTA were identified earlier in several Pakistani families with ARWH. Haplotype analysis using microsatellite markers close to the LIPH gene defined a founder haplotype shared in families from Pakistan and Guyana. Proteomic analysis of hair shaft samples from one of the families revealed no substantial changes among the proteins identified, indicating that the syndrome does not involve global alterations in protein expression. Our results further suggest a crucial role of LIPH gene in hair growth.
Title: Effects of methanol extract of Uncariae Ramulus et Uncus on ibotenic acid-induced amnesia in the rat Kim JH, Chung JY, Lee YJ, Park S, Hahm DH, Lee HJ, Shim I Ref: J Pharmacol Sci, 96:314, 2004 : PubMed
In the present study, we investigated the effects of Uncariae Ramulus et Uncus (UR) on learning and memory in the Morris water maze task and the central cholinergic system of rats with excitotoxic medial septum (MS) lesion. In the water maze test, the animals were trained to find a platform in a fixed position during 6 days and then received a 60-s probe trial in which the platform was removed from the pool on the 7th day. Ibotenic lesion of the MS showed impaired performance of the maze test and severe cell losses in the septohippocampal cholinergic system (SHC), as indicated by decreased choline acetyltransferase-immunoreactivity and acetylcholinesterase-reactivity in the hippocampus. Daily administrations of UR (100 mg/kg, i.p.) for 21 consecutive days produced significant reversals of ibotenic acid-induced deficit in learning and memory. These treatments also reduced the loss of cholinergic immunoreactivity in the hippocampus induced by ibotenic acid. These results demonstrated that impairments of spatial learning and memory may be attributable to degeneration of SHC neurons and that UR ameliorated learning and memory deficits partly through neuroprotective effects on the central acetylcholine system. Our studies suggest that UR may be useful in the treatment of Alzheimer's disease.
Title: Novel anticholinesterase and antiamnesic activities of dehydroevodiamine, a constituent of Evodia rutaecarpa Park CH, Kim SH, Choi W, Lee YJ, Kim JS, Kang SS, Suh YH Ref: Planta Med, 62:405, 1996 : PubMed
To find a new compound with antiamnesic activity, we screened 29 natural products for their abilities to inhibit acetylcholinesterase and reverse scopolamine-induced amnesia. Among the plants tested Evodia rutaecarpa Bentham showed a strong inhibitory effect on acetylcholinesterase in vitro and an anti-amnesic effect in vivo. By sequential fractionation of E. rutaecarpa, the active component was finally identified as dehydroevodiamine hydrochloride (DHED). DHED inhibited acetylcholinesterase activity in a dose-dependent and non-competitive manner. The IC50 value of DHED is 37.8 microM. A single administration of DHED to rats (6.25 mg/kg) significantly reversed the scopolamine-induced memory impairment in a passive avoidance test. The antiamnesic effect of DHED was more potent than that of tacrine which is the only drug for Alzheimer's disease approved by FDA. This potent antiamnesic effect of DHED was thought to be due to the combined effects of acetylcholinesterase inhibition and the known cerebral blood flow enhancement. These results indicate that DHED has novel anti-cholinesterase and antiamnesic activities and might have therapeutic potential in various disorders including Alzheimer's disease.
