• 대한한의학회지
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• 제39권3호
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• pp.1-16
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• 2018

Objectives: The purpose of this study was to investigate the effects of 56 herbal formulae covered by the National Health Insurance Corporation (NHIC) on dementia-related biomarkers and neuronal cell changes. Methods: The 56 herbal formulae were extracted with 70% ethanol at $100^{\circ}C$ for 2 h. The antioxidant properties was measured by radical scavenging assay using ABTS+ radical. The acetylcholinesterase (AChE) activity was tested by Ellman's assay and $amyloid-{\beta}$ ($A{\beta}$) aggregation was determined using fluorescence method. To estimate the inhibitory effects of herbal formulae on neuronal cell death and inflammation using HT22 hippocampal cells and BV-2 microglia, respectively. Results: Among the 56 herbal formulae, Dangguiyukhwangtang, Banhasasimtang, Samhwangsasimtang, Cheongwiesan, Hwangryunhaedoktang, Banhabaekchulchunmatang, Jaeumganghwatang, Cheongseoikgitang, and Hoechunyanggyuksan has a significant inhibitory effects on acetylcholinesterase (AChE) activity. Doinseunggitang and Samhwangsasimtang exerted the effect on the inhibition of $amyloid-{\beta}$ ($A{\beta}$) aggregation. Additionally, 10 herbal formulae affected AChE and $A{\beta}$ aggregation revealed antioxidant activity as well as neuroprotective and anti-neuroinflammation effects in neuronal cell lines. Conclusions: 10 herbal formulae that have been shown to be effective against the major dementia markers have been shown to have antioxidant activity, neuronal cell protection and inhibition of brain inflammation. Further investigation of these herbal formulae will need to be validated in dementia animal models.

• 동의생리병리학회지
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• 제28권3호
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• pp.317-321
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• 2014

Amyloid-${\beta}$ protein ($A{\beta}$) is a pathological component of Alzheimer's disease (AD) by participating in the senile plaque formation in the patient's brain. Although the exact mechanism of $A{\beta}$ toxicity is not fully elucidated, it is considered to be closely related to its fibrillation process. For prevention of AD, recent studies have suggested various small molecules which inhibit $A{\beta}$ fibrillation. In this report, ${\beta}$-asarone found in acorus plant has been investigated as an anti-amyloid molecule. ${\beta}$-Asarone was demonstrated to prevent in vitro fibrillation of $A{\beta}$ by inducing the oligomer formation that obviously decreased cytotoxicity. Therefore, ${\beta}$-asarone could be suggested as an inhibitory agent of $A{\beta}$ fibrillation and toxicity, which would help us not only to understand underlying principle of amyloidogenesis mechanism but also to develop a controlling strategy toward AD.

• 생물정신의학
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• 제5권1호
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• pp.66-70
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• 1998

Apoptosis is a form of cell death in which the cells shrink and exhibit nuclear chromatin condensation and DNA fragmentation, and yet maintain membrane integrity. Many lines of evidence have shown that brain neurons are vulnerable to degeneration by apoptosis. Also it has been suggested that apoptosis is one of the mechanism contributing neuronal loss in Alzheimer's disease(AD), since the conditions in the disease($A{\beta}$ peptide, oxidative stress, low energy metabolism) are the inducers that activate apoptosis. Indeed some neurons in vulnerable regions of the AD brain show DNA damage, chromatin condensation, and apoptic bodies. Consistently, mutations in AD causative genes(Amyloid precursor protein, Presenilin-1 and Presenilin- 2) increase $A{\beta}$ $peptide_{1-42}(A{\beta}_{1-42})$ and sensitize neuronal cell to apoposis. However, several lines of evidence have shown that the location of neuronal loss and $A{\beta}$ peptide deposition is not correlated in AD brain and transgenic mice brain over-expressing $A{\beta}_{1-42}$. Taken together, these data may indicated that $A{\beta}$ peptide(and other causative factors of AD) can interact with other cellular insults or risk factors to exacerbate pathological mechansim of AD through apoptosis. Thus, this review discusses possible role and mechanism of apoptosis in AD.

• Molecules and Cells
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• 제24권1호
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• pp.69-75
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• 2007

Alzheimer's disease is a neurodegenerative disorder associated with progressive loss of cognitive function and memory. Amyloid beta peptide ($A{\beta}$) is the major component of senile plaques and is known to exert its cytotoxic effect mainly by producing $H_2O_2$. Vascular endothelial growth factor (VEGF) is elevated in the cerebrospinal fluid (CSF) and brain of AD patients, and $H_2O_2$ is one of the factors that induce VEGF. Therefore, we tested whether $A{\beta}$ might be responsible for the increased VEGF synthesis. We found that $A{\beta}$ induced the production of $H_2O_2$ in vitro. Comparison of the amount of $H_2O_2$ required to induce VEGF synthesis in HN33 cells and the amount of $H_2O_2$ produced by $10{\mu}M\;A{\beta}_{1-42}$ in vitro suggested that a toxic concentration of $A{\beta}$ might induce VEGF synthesis in these cells. However, toxic concentrations of $A{\beta}$ failed to induce VEGF synthesis in several cell systems. They also had no effect on antioxidant enzymes such as glutathione peroxidase, catalase, and peroxiredoxin in HN33 cells. $Cu^{2+}$, $Zn^{2+}$ and $Fe^{3+}$ are known to accumulate in the brains of AD patients and promote aggregation of $A{\beta}$, and $Cu^{2+}$ by itself induces synthesis of VEGF. However, there was no synergistic effect between $Cu^{2+}$ and $A{\beta}_{1-42}$ in the induction of VEGF synthesis and $Zn^{2+}$ and $Fe^{3+}$ also had no effect on the synthesis of VEGF, alone or in combination with $A{\beta}$.

• Molecules and Cells
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• 제24권1호
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• pp.113-118
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• 2007

The brains of Alzheimer's disease (AD) patients are characterized by large deposits of amyloid beta peptide ($A{\beta}$). $A{\beta}$ is known to increase free radical production in nerve cells, leading to cell death that is characterized by lipid peroxidation, free radical formation, protein oxidation, and DNA/RNA oxidation. In this study, we selected an extract of Gardenia jasminoides by screening, and investigated its ameliorating effects on $A{\beta}$-induced oxidative stress using PC12 cells. The effects of the extract were evaluated using the 2',7'-dichlorofluorescein diacetate (DCF-DA) assay and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. To find the active component, the ethanol extract was partitioned with hexane, chloroform, and ethyl acetate, respectively, and the active component was purified by silica-gel column chromatography and HPLC. The results suggested that Gardenia jasminoides extract can reduce the cytotoxicity of $A{\beta}$ in PC 12 cells, possibly by reducing oxidative stress.

• 대한의생명과학회지
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• 제21권1호
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• pp.1-8
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• 2015

Alzheimer's disease is a common form of dementia occurring among the elderly population and can be identified by symptoms such as cognition impairments, memory loss and neuronal dysfunction. Alzheimer's disease was found to be caused by the deposition of $\beta$-amyloid plaques and neurofibrillary tangles. In addition, mutation in the APP (Amyloid precursor protein), Presenilin 1 (PSEN1) and Presenilin 2 (PSEN2) genes were also found to contribute to Alzheimer's disease. Since the potential conformational diagnosis of Alzheimer's disease requires histopathological tests on brain through autopsy, potential early diagnosis still remains challenging. In recent years, several researches have proposed the use of biomarkers for early diagnosis. In cerebrospinal fluid (CSF), $\beta$-amyloid(1-42), phosphorylated-tau and total tau were suggested to be effective biomarkers for Alzheimer's disease diagnosis. However, a single biomarker might not be sufficient for potential diagnosis of Alzheimer's disease. Thus, the use of RNA interference (RNAi) through microRNAs (miRNAs) has been proposed by several researchers for simultaneous analysis of several biomarkers using microarray technology. These miRNA based biomarkers can be analysed from both blood and CSF, but miRNAs from blood are advantageous over CSF as they are non-invasive and simple for collection. Moreover, the RNAi based therapeutics by siRNA (short interference RNA) or shRNA (short hairpin RNA) have also been proposed to be effective in the treatment of Alzheimer's disease. This review describes the promising application of RNAi technology in therapeutics and as a biomarker for both Alzheimer's disease diagnosis and treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2253-2255
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• 2012

Objective: The objective of our present study was to assess the role of serum amyloid A (SAA) in stages and prognosis of renal cell carcinoma. Material and Methods: It was a hospital based retrospective study carried out in the Department of Medicine and Biochemistry of Manipal Teaching Hospital, Pokhara, Nepal between $1^{st}$ January 2008 and $31^{st}$ December 2011. The variables collected were SAA, CRP. Approval for the study was obtained from the institutional research ethical committee. Quantitative analysis of human SAA and C-reactive protein (CRP) was performed by radial immune diffusion (RID) assay for all cases. Results: Of the 422 total cases of renal cell carcinoma, 218 patients had normal and 204 abnormal SAA. SAA levels were grossly elevated in T3 stage ($122.3{\pm}SD35.7$) when compared to the mean for the T2 stage ($84.2{\pm}SD24.4$) (p value: 0.0001). Similarly, SAA levels were grossly elevated in M1 stage ($190.0{\pm}SD12.7$) when compared to the M0 stage ($160.9{\pm}SD24.8$) (p: 0.0001). There was no significant association with elevated CRP levels ($209.1{\pm}SD22.7$, normal $199.0{\pm}SD19.5$). Conclusion: The validity of SAA in serum as being of independent prognostic significance in RCC was demonstrated with higher levels in advanced stage disease.

• 한국수산과학회지
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• 제50권1호
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• pp.85-91
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• 2017

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of insidious onset that causes gradual loss of memory and cognitive function, and it is the most common form of dementia in the elderly. AD is characterized by neuritic plaques and neurofibrillary tangles in the brain, together with loss of neuronal cells. The major neuropathological hallmark of AD is the accumulation of extracellular neurotoxic ${\beta}-amyloid$ ($A{\beta}$) peptides, such as $A{\beta}1-42$, in the brain. In the present study, we investigated the effect of sargachromenol (SCM), sargaquinoic acid (SQA) and sargahydroquinoic acid (SHQA) isolated from Sargassum serratifoilum ethanol extract (SSE) on $A{\beta}$ production in vitro using APP751-transfected Chinese hamster ovary cells (CHO-751). CHO-751 cells were treated with various concentrations of SSE, SCM, SQA and SHQA, and the level of extracellular $A{\beta}1-42$ was evaluated by enzyme-linked immunosorbent assay. SSE and SHQA reduced the production of $A{\beta}1-42$ in CHO-751 cells. Therefore, SHQA isolated from S. serratifolium has potential as an inhibitor of neurotoxic $A{\beta}$ peptide production.

• Nutrition Research and Practice
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• 제10권3호
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• pp.274-281
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• 2016

BACKGROUND/OBJECTIVES: The accumulation of amyloid-${\beta}$ ($A{\beta}$) in the brain is a hallmark of Alzheimer's disease (AD) and plays a key role in cognitive dysfunction. Perilla frutescens var. japonica extract (PFE) and its major compound, rosmarinic acid (RA), have shown antioxidant and anti-inflammatory activities. We investigated whether administration of PFE and RA contributes to cognitive improvement in an $A{\beta}_{25-35}$-injected mouse model. MATERIALS/METHODS: Male ICR mice were intracerebroventricularly injected with aggregated $A{\beta}_{25-35}$ to induce AD. $A{\beta}_{25-35}$-injected mice were fed PFE (50 mg/kg/day) or RA (0.25 mg/kg/day) for 14 days and examined for learning and memory ability through the T-maze, object recognition, and Morris water maze test. RESULTS: Our present study demonstrated that PFE and RA administration significantly enhanced cognition function and object discrimination, which were impaired by $A{\beta}_{25-35}$, in the T-maze and object recognition tests, respectively. In addition, oral administration of PFE and RA decreased the time to reach the platform and increased the number of crossings over the removed platform when compared with the $A{\beta}_{25-35}$-induced control group in the Morris water maze test. Furthermore, PFE and RA significantly decreased the levels of nitric oxide (NO) and malondialdehyde (MDA) in the brain, kidney, and liver. In particular, PFE markedly attenuated oxidative stress by inhibiting production of NO and MDA in the $A{\beta}_{25-35}$-injected mouse brain. CONCLUSIONS: These results suggest that PFE and its active compound RA have beneficial effects on cognitive improvement and may help prevent AD induced by $A{\beta}$.

• The Korean Journal of Physiology and Pharmacology
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• 제24권4호
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• pp.299-310
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• 2020

Alzheimer's disease (AD) is a multi-faceted neurodegenerative disease. Thus, current therapeutic strategies require multitarget-drug combinations to treat or prevent the disease. At the present time, single drugs have proven to be inadequate in terms of addressing the multifactorial pathology of AD, and multitarget-directed drug design has not been successful. Based on these points of views, it is judged that combinatorial drug therapies that target several pathogenic factors may offer more attractive therapeutic options. Thus, we explored that the combination therapy with lower doses of cilostazol and aripiprazole with add-on donepezil (CAD) might have potential in the pathogenesis of AD. In the present study, we found the superior efficacies of donepezil add-on with combinatorial mixture of cilostazol plus aripiprazole in modulation of expression of AD-relevant genes: Aβ accumulation, GSK-3β, P300, acetylated tau, phosphorylated-tau levels, and activation of α-secretase/ADAM 10 through SIRT1 activation in the N2a Swe cells expressing human APP Swedish mutation (N2a Swe cells). We also assessed that CAD synergistically raised acetylcholine release and choline acetyltransferase (CHAT) expression that were declined by increased β-amyloid level in the activated N2a Swe cells. Consequently, CAD treatment synergistically increased neurite elongation and improved cell viability through activations of PI3K, BDNF, β-catenin and α7-nicotinic cholinergic receptors in neuronal cells in the presence of Aβ_1-42. This work endorses the possibility for efficient treatment of AD by supporting the synergistic therapeutic potential of donepezil add-on therapy in combination with lower doses of cilostazol and aripiprazole.