• Asian-Australasian Journal of Animal Sciences
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• 제20권5호
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• pp.768-774
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• 2007

To study the effect of dietary docosahexaenoic acid (DHA) enrichment on the expression of hepatic genes in pigs, weaned, crossbred pigs (30 d old) were fed diets supplemented with either 2% tallow or DHA oil for 18 d. Hepatic mRNA was extracted. Suppression subtractive hybridization was used to explore the hepatic genes that were specifically regulated by dietary DHA enrichment. After subtraction, we observed 288 cDNA fragments differentially expressed in livers from pigs fed either 2% DHA oil or 2% tallow for 18 d. After differential screening, 7 genes were found to be differentially expressed. Serum amyloid A protein 2 (SAA2) was further investigated because of its role in lipid metabolism. Northern analysis indicated that hepatic SAA2 was upregulated by dietary DHA enrichment (p<0.05). In a second experiment, feeding 10% DHA oil for 2d significantly increased the expression of SAA2 (compared to the 10% tallow group; p<0.05). The porcine SAA2 full length cDNA sequence was cloned and the sequence was compared to the human and mouse sequences. The homology of the SAA2 amino acid sequence between pig and human was 73% and between pig and mouse was 62%. There was a considerable difference in SAA2 sequences among these species. Of particular note was a deletion of 8 amino acids, in the pig compared to the human. This fragment is a specific characteristic for the SAA subtype that involved in acute inflammation reaction. Similar to human and mouse, porcine SAA2 was highly expressed in the liver of pigs. It was not detectable in the skeletal muscle, heart muscle, spleen, kidney, lung, and adipose tissue. These data suggest that SAA2 may be involved in mediation of the function of dietary DHA in the liver of the pig, however, the mechanism is not yet clear.

• The Korean Journal of Physiology and Pharmacology
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• 제8권4호
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• pp.173-179
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• 2004

Amyloid ${\beta}-peptide\;(A{\beta})$ contributes to the pathogenesis of Alzheimer's disease (AD), causing neuronal death through apoptosis. In this study, the neuroprotective role of BF-7, extracted form sericultural product, was examined against $A{\beta}-induced$ toxicity in cultured human neuronal cell SKN-SH. In order to know if the BF-7 has positive role on the cognition and memory in human, the mixture of BF-7, DHA and EPA (BDE) was examined using Rey Kim and K-WAIS test with 50 healthy high school student. We report here that BDE significantly attenuated $A{\beta}-induced$ apoptosis through the reduction of ROS accumulation, and diminished caspase-like protease activity. Moreover, the memory index and memory preservation, and attentative concentration of BDE treated group for 1 month were significantly improved, in contrast to the case of placebo control treated with DHA and EPA. This result represent that the BF-7 play significant positive role on learning memory. Taken together, our result suggested the natural product BF-7 is a good substance for the brain functionally and physiologically.

• The Korean Journal of Physiology and Pharmacology
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• 제11권2호
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• pp.37-43
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• 2007

Adenosine has been reported to provide cytoprotection in the central nervous systems as well as myocardium by activating cell surface adenosine receptors. However, the exact target and mechanism of its action still remain controversial. The present study was performed to examine whether adenosine has a protective effect against $A{\beta}$-induced injury in neuroglial cells. The astrocyte-derived human neuroglioma cell line, A172 cells, and $A{\beta}_{25{\sim}35}$ were employed to produce an experimental $A{\beta}$-induced glial cell injury model. Adenosine significantly prevented $A{\beta}$-induced apoptotic cell death. Studies using various nucleotide receptor agonists and antagonists suggested that the protection was mediated by $A_1$ receptors. Adenosine attenuated $A{\beta}$-induced impairment in mitochondrial functional integrity as estimated by cellular ATP level and MTT reduction ability. In addition, adenosine prevented $A{\beta}$-induced mitochondrial permeability transition, release of cytochrome c into cytosol and subsequent activation of caspase-9. The protective effect of adenosine disappeared when cells were pretreated with 5-hydroxydecanoate, a selective blocker of the mitochondrial ATP-sensitive $K^+$ channel. In conclusion, therefore we suggest that adenosine exerts protective effect against $A{\beta}$-induced cell death of A172 cells, and that the underlying mechanism of the protection may be attributed to preservation of mitochonarial functional integrity through opening of the mitochondrial ATP-sensitive $K^+$ channels.

• The Korean Journal of Physiology and Pharmacology
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• 제21권1호
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• pp.55-64
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• 2017

Progressive memory impairment such as that associated with depression, stroke, and Alzheimer's disease (AD) can interfere with daily life. In particular, AD, which is a progressive neurodegenerative disorder, prominently features a memory and learning impairment that is related to changes in acetylcholine and abnormal ${\beta}$-amyloid ($A{\beta}$) deposition in the brain. In the present study, we investigated the effects of dehydroevodiamine HCl (DHED) on cognitive improvement and the related mechanism in memory-impaired rat models, namely, a scopolamine-induced amnesia model and a $A{\beta}_{1-42}$-infused model. The cognitive effects of DHED were measured using a water maze test and a passive avoidance test in the memory-impaired rat models. The results demonstrate that DHED (10 mg/kg, p.o.) and Donepezil (1 mg/kg, p.o.) ameliorated the spatial memory impairment in the scopolamine-induced amnestic rats. Moreover, DHED significantly improved learning and memory in the $A{\beta}_{1-42}$-infused rat model. Furthermore, the mechanism of these behavioral effects of DHED was investigated using a cell viability assay, reactive oxygen species (ROS) measurement, and intracellular calcium measurement in primary cortical neurons. DHED reduced neurotoxicity and the production of $A{\beta}$-induced ROS in primary cortical neurons. In addition, similar to the effect of MK801, DHED decreased intracellular calcium levels in primary cortical neurons. Our results suggest that DHED has strong protective effects against cognitive impairments through its antioxidant activity and inhibition of neurotoxicity and intracellular calcium. Thus, DHED may be an important therapeutic agent for memory-impaired symptoms.

• Archives of Pharmacal Research
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• 제27권9호
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• pp.954-960
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• 2004

Expression of the NF-$textsc{k}$B-dependent genes responsible for inflammation, such as TNF-$\alpha$, IL-1$\beta$, and nitric oxide synthase (NOS), contributes to chronic inflammation which is a major cause of neurodegenerative diseases (i.e. Alzheimer＇s disease). Although NF-$textsc{k}$B plays a biphasic role in different cells like neurons and microglia, controlling the activation of NF-$textsc{k}$B is important for its negative feedback in either activation or inactivation. In this study, we found that ursodeoxycholic acid (UDCA) inhibited I$textsc{k}$B$\alpha$ degradation to block expression of the NF-$textsc{k}$B-dependent genes in microglia when activated by $\beta$-amyloid peptide (A$\beta$). We also showed that when microglia is activated by $A\beta$42, the expression of A20 is suppressed. These findings place A20 in the category of ' protective ' genes, protecting cells from pro-inflammatory reper-toires induced in response to inflammatory stimuli in activated microglia via NF-$textsc{k}$B activation. In light of the gene and proteins for NF-$textsc{k}$B-dependent gene and inactivator for NF-$textsc{k}$B (I$textsc{k}$B$\alpha$), the observations now reported suggest that UDCA plays a role in supporting the attenuation of the production of pro-inflammatory cytokines and NO via inactivation of NF-$textsc{k}$B. Moreover, an NF-$textsc{k}$B inhibitor such as A20 can collaborate and at least enhance the anti-inflammatory effect in microglia, thus giving a potent benefit for the treatment of neurodegenerative diseases such as AD.uch as AD.

• Preventive Nutrition and Food Science
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• 제12권2호
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• pp.74-78
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• 2007

Fucoidan, that is high-molecular-weight sulfated polysaccharides extracted from brown seaweeds has been shown to elicit various biological activities. Here, we investigated the effects of fucoidan on cell proliferation and nitric oxide (NO) production in neuronal blastoma cell (SH-SY5Y). In the present study, we demonstrated that fucoidan treatment resulted in increase of cell proliferation and NO production. When cells were treated with amyloid-${\beta}$ (A${\beta}$) in the absence or presence of fucoidan, fucoidan recovered the cell viability decreased by A${\beta}$ peptides. To further determine whether nitric oxide synthase (NOS) is involved in proliferative effect of fucoidan, cells were treated with NOS inhibitors in the absence or presence of fucoidan. Selective constitutive nitric oxide synthase (cNOS) inhibitor, diphenylene iodonium chloride (DPI), caused a decrease of cell viability, whereas cell viability was increased by specific inducible nitric oxide synthase (iNOS) inhibitor, S-methylisothiourea (SMT), in the fucoidan-untreated cells. Treatment with fucoidan inhibited the cell viability decreased in DPI-exposed cells. In contrast, fucoidan had no effect on cell growth in SMT-treated cells, indicating that cNOS may not play a role in the proliferation of fucoidan-treated cells. The present data suggest that fucoidan has proliferative and neuroprotective effects and these effects may be associated with iNOS.

• 동의신경정신과학회지
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• 제17권2호
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• pp.75-89
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• 2006

Objective : This experiment was designed to investigate the effect of Rhododendron simsii Planch(RSP) on the Alzheimer's disease. Method : The effects of RSP on amyloid precursor proteins(APP), acetylcholinesterase (AChE), glial fibrillary acidic protein(GFAP) mRNA of PC-12 cell treated by amyloid ${\beta}$ protein$(A{\beta})$ and $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ mRNA of THP-1 cell treated by lipopolysaccharide(LPS), AChE activity of PC-12 cell lysate treated by $A{\beta}$ and behavior of the memory deficit mice induced by scopolamine, and glucose, AChE in serum of the memory deficit mice induced by scopolamine were investigated, respectively. Result : 1. RSP suppressed APP, AChE, GFAP mRNA in PC-12 celt treated by $A{\beta}$. 2. RSP suppressed $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ mRNA in THP-1 cell treated by LPS. 3. RSP suppressed AChE activity in cell lysate of PC-12 cell treated by $A{\beta}$. 4. RSP increased glucose and decreased AChE significantly in the serum of the memory deficit mice induced by scopolamine. 5. RSP group showed significantly inhibitory effect on the scopolamine-induced impairment of teaming and. memory in the experiment of Morris water maze. Conclusion : According to the above results, it is suggested that RSP might be usefully applied for prevention and treatment of Alzheimer's disease and memory deficit symptom.

• 동의신경정신과학회지
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• 제20권1호
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• pp.235-247
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• 2009

Objectives : Ginseng Radix Rubra water extract(RGE) has been used in vivo test for its beneficial effects on neuronal survival and neuroprotective functions, particularly in connection with APP-related dementias and Alzheimer's disease (AD). APP derived from proteolytic processing of the ${\beta}$-amyloid precursor protein (APP), including the amyloid-${\beta}$ peptide (A${\beta}$), plays a critical role in the pathogenesis of Alzheimer's dementia. Methods : We determined that RGE inhibits formation of APP, which are the behavior, and possibly causative, feature of AD. Results and Conclusions : In the cells, RGE significantly activated antiapoptosis and decreased the activity of APP-grim, a key enzyme in the apoptosis cell-signaling cascade. These results suggest that neuronal damage in AD might be due to two factors: a direct APP toxicity and multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of APP, underlie the neuroprotective effects of RGE.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2006년도 Spring Conference
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• pp.139-149
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• 2006

Amyloid beta (A$\beta$) is believed one of the major pathogens of Alzheimer's disease (AD), and the reduction of A$\beta$ is considered a primary therapeutic target. Immunization with A$\beta$ can reduce A$\beta$ burden and pathological features in transgenic AD model mouse. This means anti-A$\beta$ autoantibodies may have a role in AD pathology. Recent findings suggest anti-A$\beta$ autoantibodies level decrease in AD patients. The early detection of AD is important for treatment of this disease. However, diagnosis on AD has only been possible through limited methods such as neuropsychological examination or MRI. To investigate whether it was possible to detect the presence and different levels of naturally occurring anti-A$\beta$ autoantibodies in the plasma of patients with AD and age-matched controls. An advanced ELISA was performed to detect levels of naturally occurring anti-A$\beta$ autoantibodies in the plasma. The level of anti-A$\beta$ auto-antibodies from patients with idiopathic Parkinson's disease or stroke and from normal controls were compared to that of AD patients. Our results showed a significantly lower anti-A$\beta$ autoantibodies level in AD compared to those with other neurological diseases or control. The level of anti-A$\beta$ autoantibodies in the serum may be used to diagnose the presence of AD.

• Biomolecules & Therapeutics
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• 제15권4호
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• pp.205-211
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• 2007

The fruits and stems of Opuntia ficus-indica var. saboten have been reported to exhibit a variety of pharmacological actions, including antioxidant, analgesic, anti-inflammatory, and anti-ulcer effects. In the present study, we evaluated effects of the butanol fraction (SK OFB901) prepared from the 50% ethanol extract of the stems on various types of neuronal injuries induced by oxidative stress, excitotoxins, and amyloid ${\beta}\;(A_{\beta})$ in primary cultured rat cortical cells. Its antioxidant and radical scavenging activities were also evaluated by cell-free bioassays. We found that SK OFB901 strongly inhibited the oxidative neuronal damage induced by $H_2O_2$ or xanthine/xanthine oxidase. In addition, it exhibited marked inhibition of the excitotoxic neuronal damage induced by glutamate, N-methyl-D-aspartic acid, or kainate. Furthermore, the $A_{\beta(25-35)}$-induced neurotoxicity was also significantly attenuated by SK OFB901. It was found to inhibit lipid peroxidation initiated by $Fe^{2+}$ and L-ascorbic acid in rat brain homogenates and scavenge 1,1-diphenyl-2-picrylhydrazyl free radicals. These results indicate that the butanol fraction prepared from the stems of Opuntia ficus-indica var. saboten exerts potent antioxidant and neuroprotective effects through multiple mechanisms, implying its potential applications for the prevention or management of neurodegenerative disorders associated with oxidative stress, excitotoxicity, and $A{\beta}$.