• Title/Summary/Keyword: acetylcholine

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Neuroprotective effects of Extract of Broccoli, Cultivated in Desalinated Magma Seawater, on neuron-like SH-SY5Y cells (제주도 탈염 용암해수 재배로 제조한 브로콜리 추출물의 신경 세포 보호 효과)

  • Rhee, Jin Seol;Jang, Youn Bi;Choi, Ge Sun;Choung, Jai Jun;Kang, Seung Woo
    • Journal of the Korean Applied Science and Technology
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    • v.37 no.3
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    • pp.448-462
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    • 2020
  • Dietary nutrition is a critical lifestyle factor that can reduce the risk of future cognitive impairments caused by dementia. Accumulating evidence suggests that dietary supplementation with Sulforaphane may help the prevention of cognitive impairments and dementia. Thus, Sulforaphane-enriched broccoli extract would hold promise to improve cognitive impairments of dementia patients. Here, we have used broccoli extracts, prepared from broccoli cultivated in Magma Seawater, to test if the broccoli extracts can be dietary supplement to improve cognitive impairments. Magma Seawater originated from Jeju Island, Korea is unique in terms of containing high concentrations of usable minerals (Zinc, Vanadium and Germanium etc.). Broccoli, grown in Magma Seawater, would contain Sulforaphane and the extra amount of usable minerals. The chemical compositions of the broccoli extracts were analyzed using LC-Q-orbitrap to detect Sulforaphane and Glucoraphanin. Analysis method based on HPLC was developed for measurement of sulforaphane levels in the broccoli extracts. We have tested if the broccoli extracts have anti-apoptotic and anti-inflammatory effects on neuron-like SH-SY5Y cells. In addition, we examined if the broccoli extracts are able to upregulate expression of synaptic plasticity-associated proteins (BDNF and phospho-CREB) and to inhibit acetylcholine esterase (AchE) activity. We have shown that the broccoli extracts inhibited the apoptotic pathway and inflammatory responses. Finally, we present evidence showing that AchE activity was inhibited by the broccoli extracts, but expression of BDNF and phospho-CREB was upregulated. Taken together, these findings suggest that the broccoli extracts from Magma Seawater-grown broccoli would be a good source of dietary nutrition to improve cognitive impairments in the future.

Inhibitory effects of Electroacupuncture & Acupuncture at Hu-gye(SI03), Wijung(BL40),Hu-gye(SI03)ㆍWijung(BL40) on Neuropathic Pain in Rats (위중(委中), 후계(後谿), 위중배후계(委中配後谿) 전침(電鍼) 및 침자(鍼刺)가 백서(白鼠)의 신경병리성(神經病理性) 동통(疼痛) 억제(抑制)에 미치는 영향(影響))

  • Oh, Chang-log;Na, Chang-su;Lyu, Chung-yeol;Cho, Myung-rae
    • Journal of Acupuncture Research
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    • v.22 no.1
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    • pp.77-90
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    • 2005
  • Objective : Neuropathic pain sometimes arises from a partial peripheral nerve injury. This kind of pain is usually accompanied by spontaneous burning pain, allodynia and hyperalgesia. It has been well known that acupuncture is effective to the pain control from ancient time in Asia. However, it is not clear whether Electroacupuncture(EA) & Acupuncture(AC) can control neuropathic pain effectively. The aim of this study is to examine if Electroacupuncture&Acupuncture at Hu-gye(SI03), Wijung(BL4O), Hu-gye(SI03) Wijung(BL40) may be effective to the neuropathic pain (mechanical allodynia cold allodynia) in a rat model of neuropathic pain. Methods : A rat model of neuropathic pain was made by injurying tibial nerve and sural nerve while common peroneal nerve was maintained. After the neuropathic surgery, we examined if the rats exhibited the behavioral signs allodynia. The allodynia was assessed by stimulating the medial malleolus with von frey filament and acetone. Three weeks after the neuropathic surgery, electroacupuncture &, acupuncture stimulation was delivered to Hu-gye(SI03), Wijung(BL40), Hu-gye(SI03) Wijung(BL40) one time a day for one week. After that we examined the withdrawal response of neuropathic rats' legs by von frey filament and acetone stimulation, c-fos and AchE(Acetylcholine esterase) in the periaqe- ductal gray(PAG) of neuropathic rats' brain. Results : 1. Electroacupuncture&Acupuncture at Hu-gye(SI03), Wijung(BL40), Hu-gye(SI03) Wijung(BL4O) significantly decreased the withdrawal response of mechanically allodynia in EA-BL40+SI03 group and AC-SI03 group as compared with control group on 6th day. 2. Electroacupuncture &Acupuncture at Hu-gye(SI03), Wijung(BL40), Hu-gye (SI03) Wijung (BL40) significantly decreased the withdrawal response of chemical allodynia(cold allodynia) in EA-SI03 group, EA-BL40+SI03 group and AC-SI03 group as compared with control group on 6th day. 3. Electroacupuncture & Acupuncture at Hu-gye ( SI03), Wijung (BL40), Hu-gye (SI03) Wijung(BL40) significantly decreased the expression of c-fos in the periaqe- ductal gray(PAC) of neuropathic rats' brain in EA-BL40+SI03 group and AC-SI03 group as compared with control group. 4. Electroacupuncture&Acupuncture at Hu-gye(SI03), Wijung(BL40), Hu-gye (SI03) Wijung(BL40) significantly decreased the expression of AchE in the periaqe- ductal gray(PAG) of neuropathic rats' brain in EA-BL40+SI03 group and AC-SI03 group as compared with control group. Conclusions : Based on the above results it is assumed that Electroacupuncture at Hu-gye(SI03) Wijung(BL40) and Acupuncture at Hu-gye(SI03) can help the treatment of neuropathic pain.

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Optimization of Extraction Conditions to Obtain Functional Components from Buckwheat (Fagopyrum esculentum M.) Sprouts, using Response Surface Methodology (반응표면분석법에 의한 메밀(Fagopyrum esculentum M.) 새싹 기능성분의 추출 조건 최적화)

  • Park, Kee-Jai;Lim, Jeong-Ho;Kim, Bum-Keun;Jeong, Jin-Woong;Kim, Jong-Chan;Lee, Myung-Heon;Cho, Young-Sim;Jung, Hee-Yong
    • Food Science and Preservation
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    • v.16 no.5
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    • pp.734-741
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    • 2009
  • Response surface methodology (RSM) was used to optimize extraction conditions for functional components of buckwheat (Fagopyrum esculentum). A central composite design was applied to investigate the effects of three independent variables, namelyextraction temperature (X1), extraction time (X2), and ethanol concentration (X3), on responses including extraction yield (Y1), total phenolic content in the extract (Y2), $\alpha$-glucosidase inhibition activity (Y3), and acetylcholine esterase (ACE) inhibition activity (Y4). Data were analyzed using an expert design strategy and statistical software. The maximum yield was 24.95% (w/w) at $55.75^{\circ}C$ extraction temperature, 8.75 hextraction time, and 15.65% (v/v) ethanol. The maximum total phenolic yield was 222.45 mg/100 g under the conditions of $28.11^{\circ}C$ extraction temperature, 8.65 h extraction time, and 81.72% (v/v) ethanol. The maximum $\alpha$-glucosidase inhibition activity was 85.38% at $9.62^{\circ}C$, 7.86 h, and 57.58% (v/v) ethanol. The maximum ACE inhibition activity was 86.91% under extraction conditions of $10.12^{\circ}C$, 4.86 h, and 44.44% (v/v) ethanol. Based on superimposition of a four-dimensional RSM with respect to levels of total phenolics, $\alpha$-glucosidase inhibition activity, and ACE inhibition activity, obtained under various extraction conditions, the optimum ranges of conditions were an extraction temperature of $0-70^{\circ}C$, an extraction time of 2-8 h, and an ethanol concentration of 30-80% (v/v).

Effects of the Deer Antler Extract on Scopolamine-induced Memory Impairment and Its Related Enzyme Activities (녹용 추출물이 치매 동물모델의 기억력 개선과 관련효소 활성에 미치는 효과)

  • Lee, Mi-Ra;Sun, Bai-Shen;Gu, Li-Juan;Wang, Chun-Yan;Fang, Zhe-Ming;Wang, Zhen;Mo, Eun-Kyoung;Ly, Sun-Young;Sung, Chang-Keun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.38 no.4
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    • pp.409-414
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    • 2009
  • The aim of this study was to investigate the ameliorating effects of deer antler extract on the learning and memory impairments induced by the administration of scopolamine (2 mg/kg, i.p.) in rats. Tacrine was used as a positive control agent for evaluating the cognition enhancing activity of deer antler extract in scopolamine-induced amnesia models. The results showed that the deer antler extract-treated group (200 mg/kg, p.o.) and the tacrine-treated group (10 mg/kg, p.o.) significantly ameliorated scopolamine-induced amnesia based on the Morris water maze test. Although there was no statistical significance of brain ACh contents among the experimental groups, the brain ACh contents of the deer antler extract-treated group was slightly higher than that of the scopolamine-treated group. The inhibitory effect of deer antler extract on the acetylcholinesterase activity in the brain was significantly lower than that of scopolamine-treated group. The tacrine- and the deer antler-treated groups reduced the MAO-B activity compared to the scopolamine-treated group, but not significantly. These results suggest that the deer antler extract could be an effective agent for the prevention of the cognitive impairment induced by cholinergic dysfunction.

Onion Beverages Improve Amyloid β Peptide-Induced Cognitive Defects via Up-Regulation of Cholinergic Activity and Neuroprotection (양파(Allium cepa L.) 음료의 콜린성 활성 증가 및 뇌신경세포 보호로 인한 Amyloid β Peptide 유도에 대한 인지장애 개선 효과)

  • Park, Seon Kyeong;Kim, Jong Min;Kang, Jin Yong;Ha, Jeong Su;Lee, Du Sang;Kim, Ah-Na;Choi, Sung-Gil;Lee, Uk;Heo, Ho Jin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.11
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    • pp.1552-1563
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    • 2016
  • To examine the cognitive function of onion (Allium cepa L.) beverages (odourless and fortified), we analyzed in vitro neuronal cell protection against $H_2O_2$-induced cytotoxicity and performed in vivo tests on amyloid beta ($A{\beta}$)-induced cognitive dysfunction. Cellular oxidative stress and cell viability were evaluated by DCF-DA assay and MTT assay. These results show that fortified beverage resulted in better neuronal cell protection than odourless beverage at lower concentration ($0{\sim}100{\mu}g/mL$). Fortified beverage also showed more excellent acetylcholinesterase (AChE) inhibitory activity ($IC_{50}$: 4.20 mg/mL) than odourless beverage. The cognitive functions of odourless beverage and fortified beverage in $A{\beta}$-induced neurotoxicity were assessed by Y-maze, passive avoidance, and Morris water maze tests. The results show improved cognitive function in both groups treated with beverages. After in vivo tests, cholinergic activities were determined based on AChE inhibition and acetylcholine levels, and antioxidant activities were measured as SOD, oxidized glutathione (GSH)/total GSH ratio, and MDA levels in mouse brain tissue. In a Q-TOF UPLC/MS system, main compounds were analyzed as follows: odourless beverage (five types of sugars and three types of phenolics) and fortified beverages (six types of phenolics and two types of steroidal saponins).

Literature review and future tasks necessary to establish of Korean Dietary Reference Intake for choline (콜린의 한국인 영양소 섭취기준 제정 검토를 위한 문헌 고찰 및 향후 과제)

  • Shim, Eugene;Park, Jae-Hee;Lee, Yunjung;Park, Eunju
    • Journal of Nutrition and Health
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    • v.55 no.2
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    • pp.211-226
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    • 2022
  • Choline, an essential nutrient for humans, is required for the structural integrity of the cell membranes, methyl-group metabolism, synthesis of the neurotransmitter acetylcholine, synthesis of the membrane phospholipid components of the cell membranes, and the transport of lipids and cholesterol. Choline can be synthesized in the body, but it is insufficient to meet the daily requirements and hence it must be obtained through the diet. In the United States/Canada, Australia/New Zealand, Europe, China, and Taiwan, the adequate intake (AI) and tolerable upper intake level (UL) of choline have been established, while the establishment of the 2020 Dietary Reference Intakes for Koreans (KDRI) for choline was postponed due to the lack of a choline database for Korean foods and studies on the choline intake of Koreans. However, as part of the preparation work for the 2020 DRI revision and finalization, choline intake and the possibility of disease occurrence were verified through analysis of published data. The groundwork for the subsequent establishment of a choline DRI was laid through a literature search, evaluation, and review of the literature reported from 1949 up to 2019. This can be regarded as the culmination of this project. According to the results of randomized controlled trials (RCTs), cohort studies, case-control studies, and cross-sectional observational studies in humans, approximately 400-500 mg/day of choline intake was effective in preventing liver function damage (fatty liver), neural tube damage, cardiovascular disease, breast cancer, and cognitive function improvement. The same amount of choline intake, however, also correlated with the risk of prostate and colorectal cancer. At present, there is limited information available on choline intake and health outcomes, particularly for the Korean population. More human studies, including clinical trials on the requirements and the physiological benefits associated with dietary intake, are needed to establish the KDRI for choline.

Sesquiterpenoids Bioconversion Analysis by Wood Rot Fungi

  • Lee, Su-Yeon;Ryu, Sun-Hwa;Choi, In-Gyu;Kim, Myungkil
    • 한국균학회소식:학술대회논문집
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    • 2016.05a
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    • pp.19-20
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    • 2016
  • Sesquiterpenoids are defined as $C_{15}$ compounds derived from farnesyl pyrophosphate (FPP), and their complex structures are found in the tissue of many diverse plants (Degenhardt et al. 2009). FPP's long chain length and additional double bond enables its conversion to a huge range of mono-, di-, and tri-cyclic structures. A number of cyclic sesquiterpenes with alcohol, aldehyde, and ketone derivatives have key biological and medicinal properties (Fraga 1999). Fungi, such as the wood-rotting Polyporus brumalis, are excellent sources of pharmaceutically interesting natural products such as sesquiterpenoids. In this study, we investigated the biosynthesis of P. brumalis sesquiterpenoids on modified medium. Fungal suspensions of 11 white rot species were inoculated in modified medium containing $C_6H_{12}O_6$, $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ for 20 days. Cultivation was stopped by solvent extraction via separation of the mycelium. The metabolites were identified as follows: propionic acid (1), mevalonic acid lactone (2), ${\beta}$-eudesmane (3), and ${\beta}$-eudesmol (4), respectively (Figure 1). The main peaks of ${\beta}$-eudesmane and ${\beta}$-eudesmol, which were indicative of sesquiterpene structures, were consistently detected for 5, 7, 12, and 15 days These results demonstrated the existence of terpene metabolism in the mycelium of P. brumalis. Polyporus spp. are known to generate flavor components such as methyl 2,4-dihydroxy-3,6-dimethyl benzoate; 2-hydroxy-4-methoxy-6-methyl benzoic acid; 3-hydroxy-5-methyl phenol; and 3-methoxy-2,5-dimethyl phenol in submerged cultures (Hoffmann and Esser 1978). Drimanes of sesquiterpenes were reported as metabolites from P. arcularius and shown to exhibit antimicrobial activity against Gram-positive bacteria such as Staphylococcus aureus (Fleck et al. 1996). The main metabolites of P. brumalis, ${\beta}$-Eudesmol and ${\beta}$-eudesmane, were categorized as eudesmane-type sesquiterpene structures. The eudesmane skeleton could be biosynthesized from FPP-derived IPP, and approximately 1,000 structures have been identified in plants as essential oils. The biosynthesis of eudesmol from P. brumalis may thus be an important tool for the production of useful natural compounds as presumed from its identified potent bioactivity in plants. Essential oils comprising eudesmane-type sesquiterpenoids have been previously and extensively researched (Wu et al. 2006). ${\beta}$-Eudesmol is a well-known and important eudesmane alcohol with an anticholinergic effect in the vascular endothelium (Tsuneki et al. 2005). Additionally, recent studies demonstrated that ${\beta}$-eudesmol acts as a channel blocker for nicotinic acetylcholine receptors at the neuromuscular junction, and it can inhibit angiogenesis in vitro and in vivo by blocking the mitogen-activated protein kinase (MAPK) signaling pathway (Seo et al. 2011). Variation of nutrients was conducted to determine an optimum condition for the biosynthesis of sesquiterpenes by P. brumalis. Genes encoding terpene synthases, which are crucial to the terpene synthesis pathway, generally respond to environmental factors such as pH, temperature, and available nutrients (Hoffmeister and Keller 2007, Yu and Keller 2005). Calvo et al. described the effect of major nutrients, carbon and nitrogen, on the synthesis of secondary metabolites (Calvo et al. 2002). P. brumalis did not prefer to synthesize sesquiterpenes under all growth conditions. Results of differences in metabolites observed in P. brumalis grown in PDB and modified medium highlighted the potential effect inorganic sources such as $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ on sesquiterpene synthesis. ${\beta}$-eudesmol was apparent during cultivation except for when P. brumalis was grown on $MgSO_4$-free medium. These results demonstrated that $MgSO_4$ can specifically control the biosynthesis of ${\beta}$-eudesmol. Magnesium has been reported as a cofactor that binds to sesquiterpene synthase (Agger et al. 2008). Specifically, the $Mg^{2+}$ ions bind to two conserved metal-binding motifs. These metal ions complex to the substrate pyrophosphate, thereby promoting the ionization of the leaving groups of FPP and resulting in the generation of a highly reactive allylic cation. Effect of magnesium source on the sesquiterpene biosynthesis was also identified via analysis of the concentration of total carbohydrates. Our current study offered further insight that fungal sesquiterpene biosynthesis can be controlled by nutrients. To profile the metabolites of P. brumalis, the cultures were extracted based on the growth curve. Despite metabolites produced during mycelia growth, there was difficulty in detecting significant changes in metabolite production, especially those at low concentrations. These compounds may be of interest in understanding their synthetic mechanisms in P. brumalis. The synthesis of terpene compounds began during the growth phase at day 9. Sesquiterpene synthesis occurred after growth was complete. At day 9, drimenol, farnesol, and mevalonic lactone (or mevalonic acid lactone) were identified. Mevalonic acid lactone is the precursor of the mevalonic pathway, and particularly, it is a precursor for a number of biologically important lipids, including cholesterol hormones (Buckley et al. 2002). Farnesol is the precursor of sesquiterpenoids. Drimenol compounds, bi-cyclic-sesquiterpene alcohols, can be synthesized from trans-trans farnesol via cyclization and rearrangement (Polovinka et al. 1994). They have also been identified in the basidiomycota Lentinus lepideus as secondary metabolites. After 12 days in the growth phase, ${\beta}$-elemene caryophyllene, ${\delta}$-cadiene, and eudesmane were detected with ${\beta}$-eudesmol. The data showed the synthesis of sesquiterpene hydrocarbons with bi-cyclic structures. These compounds can be synthesized from FPP by cyclization. Cyclic terpenoids are synthesized through the formation of a carbon skeleton from linear precursors by terpene cyclase, which is followed by chemical modification by oxidation, reduction, methylation, etc. Sesquiterpene cyclase is a key branch-point enzyme that catalyzes the complex intermolecular cyclization of the linear prenyl diphosphate into cyclic hydrocarbons (Toyomasu et al. 2007). After 20 days in stationary phase, the oxygenated structures eudesmol, elemol, and caryophyllene oxide were detected. Thus, after growth, sesquiterpenes were identified. Per these results, we showed that terpene metabolism in wood-rotting fungi occurs in the stationary phase. We also showed that such metabolism can be controlled by magnesium supplementation in the growth medium. In conclusion, we identified P. brumalis as a wood-rotting fungus that can produce sesquiterpenes. To mechanistically understand eudesmane-type sesquiterpene biosynthesis in P. brumalis, further research into the genes regulating the dynamics of such biosynthesis is warranted.

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