• YAKHAK HOEJI
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• v.50 no.5
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• pp.326-331
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• 2006

We designed and synthesized new benzylpiperidinyl ether derivatives as beta-amyloid aggregation inhibitors for the development of novel anti-Alzheimer's disease agents. As starting material, 4-hydroxypiperidine was used. For protection of the amine group in piperidine (2), di-tert-butyl dicarbonate was reacted with 4-hydroxypiperidine in the presence of triethylamine. For introduction of benzyl group, benzylbromide was treated with compound 2 in dioxane. After deprotection of Boc group on amine in compound 3, ester (5) was synthesized by addition of ethyl-4-chlorobutyrate. The alcohol 6 was synthesized by hydride reduction of 5 using $LiAlH_4$. To obtain final products (7-14), the alcohol 6 was condensed with each of substituted benzoic acids. To screen beta-amyloid aggregation inhibition of the products, thioflavinT assay was performed using $A{\beta}1-42\;at\;37^{\circ}C$ for 26 h incubation, in vitro. From the result of screening, compound 8, 9, 11 and 12 showed effective activity about $65{\sim}85\;{\mu}M\;as\;IC_{50}$ value. Among the prepared compounds, 4-[4-(benzyloxy)piperidino]butyl-4-chlorobenzoate (8) was the most effective inhibitor having $IC_{50}\;of\;65.4{\mu}M$.

• Natural Product Sciences
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• v.26 no.2
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• pp.165-170
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• 2020

Carica papaya is a medicinal and fruit plant owing biological activities including antioxidant, antiviral, antibacterial and anticancer. The present study aims to investigate the acetyl (AChE) and butyryl (BChE) cholinesterase inhibitory potentials of C. papaya extracts as well as their chemical compositions. The chemical composition of the active extract was identified using a gas chromatography-mass spectrometry (GC-MS). Ellman enzyme inhibition assay showed that the alkaloid-enriched leaf extract of C. papaya possessed significant anti-BChE activity with an enzyme inhibition of 75.9%. GC-MS analysis showed that the alkaloid extract composed mainly the carpaine (64.9%) - a major papaya alkaloid, and some minor constituents such as aliphatic hydrocarbons, terpenes and phenolics. Molecular docking of carpaine revealed that this molecule formed hydrogen bond and hydrophobic interactions with choline binding site and acyl pocket. This study provides some preliminary findings on the potential use of C. papaya leaf as an herbal supplement for the prevention and treatment of Alzheimer's disease.

• Korean Journal of Plant Resources
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• v.28 no.6
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• pp.675-681
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• 2015

β amyloid protein (Aβ) plays a critical role in the pathogenesis of Alzheimer's disease (AD) and possibly in Aβ-induced mitochondrial dysfunction and oxidative stress. Aβ can directly cause reactive oxygen species (ROS) production. Overproduction of ROS is considered to be involved in the pathogenesis of neurodegeneration of AD. Here, we investigated 9 kinds of ramie (Boehmeria nivea, (L.) Gaud., BN; hereafter denoted as BN) for their protective action against oxidative stress in a cellular system using C6 glial cells. We observed loss of cell viability and high levels of ROS generation after treatment with hydrogen peroxide (H₂O₂) and Aβ_25-35. However, treatments with BN extracts led to an increase in cell viability and decrease in ROS production induced by H2O2 and Aβ25-35. In particular, the extracts of BN-01 (seobang variety from Seocheon) and BN-09 (local variety from Yeonggwang) showed excellent anti-oxidative properties. This indicates that BN extracts could prevent neurodegeneration by reducing oxidative stress in cells.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.05a
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• pp.94-94
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• 2002

Oxidative stress induced by reactive oxygen and/or nitrogen species has been considered as a major cause of cellular injuries in a variety of neurodegenerative disorders including Alzheimer's disease (AD). Inflammatory as well as oxidative tissue damage has been implicated in pathophysiology of AD, and non-steroidal anti-inflammatory drugs have been reported to have beneficial effects in the treatment or prevention of AD.(omitted)

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.327.2-327.2
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• 2002

Inflammatory as well as oxidative tissue damage has been associated with pathophysiology of Alzheimer's disease (AD), and nonsteroidal anti-inflammatory drugs have been shown to retard the progress of AD. In this study, we have investigated the molecular mechanisms underlying oxidative and inflammatory cell death induced by beta-amyloid (Abeta), a neurotoxic peptide associated with senile plaques formed in the brains of patients with AD, in cultured PC12 cells. (omitted)

• Journal of Ginseng Research
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• v.45 no.6
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• pp.665-675
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• 2021

Background: Ginsenoside Rg1 (Rg1), an active ingredient in ginseng, may be a potential agent for the treatment of Alzheimer's disease (AD). However, the protective effect of Rg1 on neurodegeneration in AD and its mechanism of action are still incompletely understood. Methods: Wild type (WT) and APP/PS1 AD mice, from 6 to 9 months old, were used in the experiment. The open field test (OFT) and Morris water maze (MWM) were used to detect behavioral changes. Neuronal damage was assessed by hematoxylin and eosin (H&E) and Nissl staining. Immunofluorescence, western blotting, and quantitative real-time polymerase chain reaction (q-PCR) were used to examine postsynaptic density 95 (PSD95) expression, amyloid beta (Aβ) deposition, Tau and phosphorylated Tau (p-Tau) expression, reactive oxygen species (ROS) production, and NAPDH oxidase 2 (NOX2) expression. Results: Rg1 treatment for 12 weeks significantly ameliorated cognitive impairments and neuronal damage and decreased the p-Tau level, amyloid precursor protein (APP) expression, and Aβ generation in APP/PS1 mice. Meanwhile, Rg1 treatment significantly decreased the ROS level and NOX2 expression in the hippocampus and cortex of APP/PS1 mice. Conclusions: Rg1 alleviates cognitive impairments, neuronal damage, and reduce Aβ deposition by inhibiting NOX2 activation in APP/PS1 mice.

• YAKHAK HOEJI
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• v.49 no.1
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• pp.103-108
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• 2005

Tacrine analogues for degenerative brain disease treatments have been designed. A series of diazaanthrine derivatives as novel analogues of tacrine has been prepared through the alkyl substitution and the ring expansion. They were expected to retain anti-inflammatory activity by inhibition of prostaglandin production with reduction of side effect as the selective prostaglandin synthase inhibitor. Prostaglandin synthase expression is associated with the deposition of beta-amyloid protein in neuritic plaques in brain inflammation. Therefore selective prostaglandin synthase blockade is important for the prevention and treatment of alzheimer's disease. To evaluate inhibitory effect of prostaglandin synthase, synthetic tacrine derivatives were screened with accumulation of prostaglandin biosynthesis by lipopolysaccharide in aspirin-treated murine macrophage cell. Most of synthetic compounds have shown significant prostaglandin synthase activities in vitro screening with $84.3{\sim}33.6\%$ inhibition of the prostaglandin $E_2$ production at $10\;{\mu}g/ml$.

• Biomolecules & Therapeutics
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• v.31 no.3
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• pp.276-284
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• 2023

Sinapic acid (SA) is a phenolic acid that is widely distributed in fruits and vegetables, which has various bioactivities, such as antidiabetic, anticancer and anti-inflammatory functions. Over-activated microglial is involved in the development progress of neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. The objective of this study was to investigate the effect of SA in microglia neuroinflammation models. Our results demonstrated that SA inhibited secretion of the nitric oxide (NO) and interleukin (IL)-6, reduced the expression of inducible nitric oxide synthase (iNOS) and enhanced the release of IL-10 in a dose-dependent manner. Besides, our further investigation revealed that SA attenuated the phosphorylation of AKT and MAPK cascades in LPS-induced microglia. Consistently, oral administration of SA in mouse regulated the production of inflammation-related cytokines and also suppressed the phosphorylation of MAPK cascades and AKT in the mouse cerebral cortex. These results suggested that SA may be a possible therapy candidate for anti-inflammatory activity by targeting the AKT/MAPK signaling pathway.

• Biomedical Science Letters
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• v.27 no.4
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• pp.248-254
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• 2021

Ulcerative colitis (UC), chronic inflammatory bowel disease, is characterized by severe inflammation in the colon. Tea is one of the most popular beverages consumed worldwide. Pu-erh tea, a unique Chinese tea produced by microbial activities, possesses a broad range of health-promoting effects, including anti-aging, anti-Alzheimer's disease, antioxidation and anti-obesity. However, the inhibitory effect of Pu-erh tea on intestinal inflammation and the underlying mechanism remain unclear. The present study was designed to evaluate the regulatory effect of Pu-erh tea extract (PTE) on dextran sulfate sodium (DSS)-induced colitis clinical signs by analyzing the weight loss and colon length in mice. The inhibitory effects of PTE on inflammatory mediators, such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, and the activation of nuclear factor-κB (NF-κB) were also determined in DSS-treated colitis tissue. We observed that PTE treatment significantly inhibited the DSS-induced clinical symptoms of weight loss, decrease,in colon length, and colon tissue damage in mice. Moreover, PTE attenuated the DSS-induced levels of IL-6 and TNF-α in colon tissue. We also demonstrated the anti-inflammatory mechanism of PTE by suppressing the activation of NF-κB in DSS-treated colon tissues. Collectively, the findings provide experimental evidence that PTE may be effective in preventing and treatment of intestinal inflammatory disorders, including UC.

• Journal of Pharmacopuncture
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• v.22 no.4
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• pp.231-238
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• 2019

Objectives: Alzheimer's disease (AD), an overwhelming neurodegenerative disease, has deleterious effects on the brain that consequently causes memory loss and language impairment. This study was intended to investigate the neuroprotective activity of the two essential oils (EOs) from Iranian Pistacia khinjuk (PK) leaves and Allium sativum (AS) cloves against β-Amyloid 25-35 (Aβ25-35) induced elevation of cholinesterase enzymes in AD. Methods: The EOs of PK (PKEO) and AS (ASEO) were prepared and analyzed in terms of extraction yield, phenolic content, and cholinergic markers in vitro. Moreover, both were administered orally to adult male Wistar rats at concentrations of 1, 2, and 3%. The inhibitory potential of PKEO and ASEO was compared with Donepezil (0.75 mg/kg) against the high activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Results: PKEO reached an inhibition rate of 83.6% and 81.4% against AChE and BChE, respectively. ASEO had lower anti-cholinesterase activity (65.4% and 31.5% for the inhibition AChE and BChE). PKEO was found to have more phenolic content than ASEO. A significantly positive correlation was observed between the total phenolics and anti-cholinesterase potential. In rats, both EOs decreased the enzyme activity in a concentration-dependent manner. As compared with Donepezil, the significant difference in the AChE and BChE inhibition occurred as rats were treated with PKEO 3% (p < 0.05). Conclusion: It could be concluded that PKEO and ASEO are potent inhibitors of AChE and BChE in rats that hold promise to be used for the treatment of AD.