• 약학회지
• /
• 제51권6호
• /
• pp.463-468
• /
• 2007

Chong Myung Tang is consisted of three medicinal herbs (Acori Graminei Rhizoma, Polygalae Radix and Hoelen cum Radix). It has been used as a medicine for the purpose of learning and memory improvement. In this paper, Chong Myung Tang was screened the biological activities for Alzheimer's disease. The extract (70% ethanol) of Acari Graminei Rhizoma (1 mg/ml) showed that acetylcholinesterase (AChE) and amyloid beta ($A{\beta}$) peptide aggregation inhibitory potency are 43.1% and 76.5%, respectively. The extract of Polygalae Radix showed inhibitory activity against $A{\beta}_{1-42}$ peptide aggregation (51.5%). To predict the drug-likeness, oral absorption ability; blood-brain barrier (BBB) penetraion rate, mutagenecity and carcinogenicity; in silico screening was performed against 16 compounds in the three medicinal herbs. According to the results, all compounds have appropriate chemical structures as medicines. The six compounds in Acori Graminei Rhizoma and the five compounds in Hoelen cum Radix showed excellent oral absorption rate and BBB penetration rate. The four compounds in Polygalae Radix showed excellent oral absorption rate, but their BBB penetration was presented low rate. And, the extract of Hoelen cum Radix didn't show AChE and $A{\beta}_{1-42}$ peptide aggregation inhibitory activities in vitro. Therefore, their activity in brain may be other mechanism. According to all of the results, in silico prediction technology is convenient and effective to determine biological active compounds in medicinal herbs.

• 한국식품저장유통학회지
• /
• 제14권2호
• /
• pp.213-219
• /
• 2007

퇴행성 뇌질환의 하나인 알츠하이머는 가벼운 기억력의 장애에서부터 전반적인 인지기능의 장애를 나타내는 질환으로 해마 (hippocampus)를 포함한 신경세포에서 세포사와 관련이 있는 것으로 보고 되어왔다. AP의 자체 독성과 산화 스트레스, $A{\beta}$ plaque에서 나오는 free radical은 세포내 $Ca^{2+}$를 높이고 이로 인해 calpain이 활성화되어 신경 세포사가 촉진되며 microtubule과 같은 cytoskeleton을 파괴시킨다. 이러한 ROS와 $A{\beta}$에 의해 유도되는 세포사멸을 보호하는 물질을 해바라기 씨 추출물을 이용하여 실험을 실시하였다. 우선 추출물이 항산화 효과 (DPPH, FRAP assay), acetylcholinesterase(AChE)의 활성 및 SH-SY5Y cell의 세포사멸에 미치는 영향을 검토하였다. 항산화 활성과 AChE에 대한 억제활성은 해바라기 씨 추출물 처리농도가 높을수록 유의적으로 높게 나타났다. $H_2O_2$와 $A{\beta}$에 의해 유도된 SH-SY5Y에 대한 세포사멸 억제효과 실험(MTT assay)에서 해바라기 씨 추출물이 모두 높은 활성을 나타내었으므로 이의 성분분리는 뇌세포 보호를 위한 좋은 식품재료가 될 수 있다.

• 한국식품저장유통학회지
• /
• 제14권4호
• /
• pp.425-430
• /
• 2007

Amyloid ${\beta}-peptide$에 의해 유도되는 세포사멸을 보호하는 물질을 검색하기 위하여 250여 식물 재료 및 식품성분으로부터 스크리닝한 결과 가장 효과가 있는 시금치 추출물을 이용하여 뇌신경세포사멸(neuronal cell death)을 어느 정도 보호할 수 있는지를 알아보았다. 시금치 추출물이 항산화 활성과 acetylcholinesterase 활성에 대한 저해효과는 시금치 추출물 처리농도가 높을수록 유의적으로 높게 나타났다. 과산화수소와 amyloid ${\beta}-peptide$에 의해 유도된 SH-SY5Y 세포주의 세포사멸에 대한 시금치추출액의 억제효과를 살펴본 결과, 과산화수소에 의한 세포사멸에 대하여 시금치 추출물은 억제효과를 나타내었으나, amyloid ${\beta}-peptide$의 경우는 세포사멸억제효과를 나타내지 않았다.

• Molecules and Cells
• /
• 제27권6호
• /
• pp.651-656
• /
• 2009

The formation of ${\beta}$-amyloid peptide ($A{\beta}$) is initiated from cleavage of amyloid precursor protein (APP) by a family of protease, ${\alpha}$-, ${\beta}$-, and ${\gamma}$-secretase. Sub W, a substrate peptide, consists of 10 amino acids, which are adjacent to the ${\beta}$-cleavage site of wild-type APP, and Sub M is Swedish mutant with double mutations on the left side of the ${\beta}$-cleavage site of APP. Sub W is a normal product of the metabolism of APP in the secretary pathway. Sub M is known to increase the efficiency of ${\beta}$-secretase activity, resulting in a more specific binding model compared to Sub W. Three-dimensional structures of Sub W and Sub M were studied by CD and NMR spectroscopy in water solution. On the basis of these structures, interaction models of ${\beta}$-secretase and substrate peptides were determined by molecular dynamics simulation. Four hydrogen bonds and one water-mediated interaction were formed in the docking models. In particular, the hydrogen bonding network of Sub M-BACE formed spread over the broad region of the active site of ${\beta}$-secretase (P5-P3'), and the side chain of P2- Asn formed a hydrogen bond specifically with the side chain of Arg235. These are more favorable to the cleavage of Sub M by ${\beta}$-secretase than Sub W. The two substrate peptides showed different tendency to bind to ${\beta}$-secretase and this information may useful for drug development to treat and prevent Alzheimer's disease.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
• /
• pp.141.2-142
• /
• 2003

beta-Amyloid (A$\beta$) peptide is the major component of senile plaques and considered to have a causal role in the development and progression of Alzheimer's disease. There has been compelling evidence supporting that $A\beta$-induced cytotoxicity is mediated through oxidative and/or nitrosative stress. Recently, considerable attention has been focused on dietary manipulation of oxidative and/or nitrosative damage. L-Egrothioneine (EGT) is a low-molecular weight naturally occurring thiol compound of dietary origin which exists in milimolar concentrations in the brain, liver, kindney, erythrocytes, ocular tissues and in seminal fluids of mammals. (omitted)

• Bulletin of the Korean Chemical Society
• /
• 제32권9호
• /
• pp.3425-3428
• /
• 2011

Apolipoprotein A-I (Apo A-I) is a major component for high density lipoproteins (HDL). A number of mimetic peptides of Apo A-I were screened from the phase-displayed random peptide library by utilizing monoclonal antibodies (A12). Mimetic peptide for A12 epitope against Apo A-I was selected as CPFARLPVEHHDVVGL (pA1). From the BLAST search, the mimetic peptide pA1 had 40% homology with Apo A-I. As a result of the structural determination of this mimotope using homo/hetero nuclear 2D-NMR techniques and NMR-based distance geometry (DG)/molecular dynamic (MD) computations, DG structure had low penalty value of 0.3-0.7 ${\AA}^2$ and the total RMSD was 0.6-1.6 ${\AA}$. The mimotope pA1 exhibited characteristic conformation including a ${\beta}$-turn from Pro[7] to His[11].

• BMB Reports
• /
• 제39권3호
• /
• pp.284-291
• /
• 2006

In this study, the cDNA of a new peptide from the venom of the scorpion, Buthotus saulcyi, was cloned and sequenced. It codes for a 64 residues peptide (Bsaul1) which shares high sequence similarity with depressant insect toxins of scorpions. The differences between them mainly appear in the loop1 which connects the $\beta$-strand1 to the $\alpha$-helix and seems to be functionally important in long chain scorpion neurotoxins. This loop is three amino acids longer in Bsaul1 compared to other depressant toxins. A comparative amino acid sequence analysis done on Bsaul1 and some of $\alpha$-, $\beta$-, excitatory and depressant toxins of scorpions showed that Bsaul1 contains all the residues which are highly conserved among long chain scorpion neurotoxins. Structural model of Bsaul1 was generated using Ts1 (a $\beta$-toxin that competes with the depressant insect toxins for binding to $Na^+$ channels) as template. According to the molecular model of Bsaul1, the folding of the polypeptide chain is being composed of an anti-parallel three-stranded $\beta$-sheet and a stretch of $\alpha$-helix, tightly bound by a set of four disulfide bridges. A striking similarity in the spatial arrangement of some critical residues was shown by superposition of the backbone conformation of Bsaul1 and Ts1.

• Food Science and Biotechnology
• /
• 제17권6호
• /
• pp.1165-1170
• /
• 2008

The deposition of the amyloid $\beta}$ ($A{\beta}$)-peptide following proteolytic processing of amyloid precursor protein (APP) by $\beta$-secretase (BACE1) and $\gamma$-secretase is critical feature in the progress of Alzheimer's disease (AD). Consequently, BACE1, a key enzyme in the production of $A{\beta}$, is a prime target for therapeutic intervention in AD. In the course of searching for BACE1 inhibitors from natural sources, the ethyl acetate fraction of Petasites japonicus showed potent inhibitory activity. Two BACE1 inhibitors quercetin (QC) and kaempferol 3-O-(6"-acetyl)-$\beta$-glucopyranoside (KAG) were isolated from P. japonicus by activity-guided purification. QC, in particular, non-competitively attenuated BACE1 activity with $IC_{50}$ value of $2.1{\times}10^{-6}\;M$ and $K_i$ value of $3.7{\times}10^{-6}\;M$. Both compounds exhibited less inhibition of $\alpha$-secreatase (TACE) and other serine proteases including chymotrypsin, trypsin, and elastase, suggesting that they ere relatively specific and selective inhibitors to BACE1. Furthermore, both compounds significantly reduced the extracellular $A{\beta}$ secretion in $APP_{695}$-transfected B103 cells.

• 한국미생물·생명공학회지
• /
• 제19권6호
• /
• pp.598-603
• /
• 1991

신규 미생물 Bacillus subtilis subsp. krictiensis의 배양액으로부터 식물 및 인체 병원균에 폭넓은 항진균 활성을 나타내는 DRF-001으로 총칭되는 6개의 cyclic peptide의 복합체(A에서 F)를 분리하였다. 이 6개 peptides의 분자량은 FAB-MS 측정결과, A가 1042, B와 C가 1056, D와 E가 1070 그리고 F가 1084였다. 이 복합체의 구조를 각종 자기분석을 통해 해석한 결과, 구조 중에 1몰씩의 glutamine, proline, tyrosine, serine 및 unusal $\beta$-amino acid와 3몰의 asparagine을 공통적으로 갖고 있으나, $\beta$-amino acid의 탄소수와 말단 methyl 구조에 차이점이 있음을 알 수있었다. 구성 amino acid들의 서열과 입체구조 결정에 의하여 KRF-001의 잠정구조를 결정하였다.

• Asian-Australasian Journal of Animal Sciences
• /
• 제29권3호
• /
• pp.315-320
• /
• 2016

Porcine beta-defensin-1 (PBD-1) gene plays an important role in the innate immunity of pigs. The peptide encoded by this gene is an antimicrobial peptide that has direct activity against a wide range of microbes. This peptide is involved in the co-creation of an antimicrobial barrier in the oral cavity of pigs. The objective of the present study was to detect polymorphisms, if any, in exon-1 and exon-2 regions of PBD-1 gene in Large White Yorkshire (LWY) and native Ankamali pigs of Kerala, India. Blood samples were collected from 100 pigs and genomic DNA was isolated using phenol chloroform method. The quantity of DNA was assessed in a spectrophotometer and quality by gel electrophoresis. Exon-1 and exon-2 regions of PBD-1 gene were amplified by polymerase chain reaction (PCR) and the products were subjected to single strand conformation polymorphism (SSCP) analysis. Subsequent silver staining of the polyacrylamide gels revealed three unique SSCP banding patterns in each of the two exons. The presence of single nucleotide polymorphisms (SNPs) was confirmed by nucleotide sequencing of the PCR products. A novel SNP was found in the 5'-UTR region of exon-1 and a SNP was detected in the mature peptide coding region of exon-2. In exon-1, the pooled population frequencies of GG, GT, and TT genotypes were 0.67, 0.30, and 0.03, respectively. GG genotype was predominant in both the breeds whereas TT genotype was not detected in LWY breed. Similarly, in exon-2, the pooled population frequencies of AA, AG, and GG genotypes were 0.50, 0.27, and 0.23, respectively. AA genotype was predominant in LWY pigs whereas GG genotype was predominant in native pigs. These results suggest that there exists a considerable genetic variation at PBD-1 locus and further association studies may help in development of a PCR based genotyping test to select pigs with better immunity.