• Journal of Microbiology and Biotechnology
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• 제13권5호
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• pp.778-782
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• 2003

In the course of screening anti-influenza agents from natural products, four neuraminidase inhibitors were isolated from the methanol extract of mushroom Microphorus affinis by purification using solvent partition, silica gel column chromatography, Sephadex LH-20, and semi-preparative HPLC. The chemical structures of these compounds were identified as ${\alpha}-lupeol$, methyl linoleate, methyl palmitate, and methyl oleate by means of spectral data including GC-MS, $^1H-,\;and\;^{13}C-NMR\;with\;IC_{50}$ values of 5.65, 7.07, 7.12, and $7.52\;\mu\textrm{M}$, respectively. They did not inhibit other glycosidases such as glucosidase, mannosidase, and galactosidase, indicating that they were relatively specific inhibitors of neuraminidase. The relationship between the fatty acid structure and inhibitory activity was investigated. The result showed that, in the case of an aliphatic linear hydrocarbon skeleton, at least one carboxyl (presumably any carbonyl) moiety and sixteen carbons were the necessary requirements for potent inhibition, whereas saturated, unsaturated, free, and ester forms did not have any significant effect on the activity.

• Archives of Pharmacal Research
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• 제26권5호
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• pp.367-374
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• 2003

In the course of screening neuraminidase inhibitors from herbal medicines, Reynoutria elliptica exhibited high inhibitory activity. Four active compounds were isolated from the ethyl acetate soluble fraction by consecutive purification using sillica gel, Sephadex LH-20 chromatography, and recrystallization. The chemical structures of these compounds were identified as 1,3,8-trihydroxy-6-methylanthraquinone (emodin) 1,8-dihydroxy-3-methoxy-6-methylanthraquinone (emodin 3-methyl ether; physcion), 1,3,8-trihydroxy-6-hydoxymethylanthraquinone ($\omega$-hydroxyemodin), and 3,5,4 -trihydroxystilbene (trans-resvertrol) by spectral data including MS, $^1 H-, and ^{13}C-NMR. The IC_{50}$ values of emodin, emodin 3-methyl ether, $\omega$-hydroxyemodin, and trans-resvertrol were 2.81, 74.07, 10.49, and 8.77 $\mu$M, respectively. They did not inhibit other glycosidase such as glucosidase, mannosidase, and galactosidase, indicating that they were relatively specific inhibitors of neuraminidase.

• 생명과학회지
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• 제34권9호
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• pp.656-665
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• 2024

효소 억제제는 인체 내 다양한 대사과정을 조절하는 단백질에 속하는 효소의 작용을 억제하여 특정 질병이나 상태를 치료하는 데 도움을 준다. 퀘르세틴은 폴리페놀 계열에 속하는 플라보노이드의 일종으로 식물에서 발견되는 이차 대사산물이다. 이러한 퀘르세틴은 구조적 이점을 바탕으로 효소의 활성부위에 결합하여 α-glucosidase, acetylcholinesterase, bacterial neuraminidase, xanthine oxidase에 대한 억제 활성을 갖는 것으로 보고된다. 또한, 퀘르세틴은 glycosylation, methoxylation, alkylation 등을 통해 특징적인 치환기를 가질 수 있으며 이러한 천연 퀘르세틴 유도체는 효소 활성 부위의 촉매 잔기와 특이적인 결합 패턴을 나타내어 더욱 우수한 효소저해활성을 가질 수 있다. 따라서, 본 논문에서는 퀘르세틴 및 그 유도체의 특징적인 구조에 대해 알아보고 이들의 효소저해활성을 통해 유도체별 다양한 질병을 목표로 하는 효과적인 효소 저해제 개발에 유망한 후보가 될 수 있음을 시사한다.

• 약학회지
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• 제58권1호
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• pp.71-79
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• 2014

Although Korean patients with type 2 diabetes mellitus (T2DM) are generally treated by western medicine, many of them strongly believe in the traditional oriental Sasang constitutional classification and depend on it for food, health supplements, and oriental medicines decision making. Sasang constitutional classification is a part of traditional Korean medicine that divides people into four constitutional types (Tae-Yang: TY, Tae-Eum: TE, So-Yang: SY, and So-Eum: SE), which differ in inherited characteristics such as appearance, personality traits, susceptibility to diseases, and drug responses. It is recommended for T2DM patients to control their blood glucose very well from early stages with drugs and diet. However, many T2DM patients respond differently to their drugs, even though they receive the same medicine. Therefore, the present study investigated whether Sasang constitutional type can explain the therapeutic differences between oral hypoglycemic agents (OHAs) therapy (mono, dual and triple drug therapy). Patients of 618 with T2DM diagnosis and Sasang constitutional type known who received both western and oriental medicine treatment in a hospital between April 2006 and April 2013 retrospectively studied. HbA1c (%) and blood glucose (mg/dl) levels before OHAs therapy and 3 month after were collected for metformin (MET) or sulfonylurea (SU) monotherapy, MET+SU dual therapy, MET+except SU (where was either alpha-glucosidase inhibitor, dipeptidyl peptidase-4 inhibitor, meglitinide or thiazolidinedione) dual therapy, and triple therapy, according to Sasang constitutional type. For statistical analysis, ANOVA was used and paired t-test by SPSS 19.0 where P values less than 0.05 were considered statistically significant. Pattern was similar levels of HbA1c and blood glucose and which was decreased in order of mono, MET+SU dual, MET+except SU dual and triple therapy. In all patients comparison, for the So-yang (SY) constitutional type, either monotherapy was less effective; for Te-eum (TE) type, MET+SU dual therapy was less effective while MET+except SU dual therapy was more effective and the triple therapy was less effective; and for So-eum (SE) type, the triple therapy was more effective. For the management of TE type it is recommended to use drugs except SU when dual therapy is needed, restrict triple therapy and consider dual and insulin therapy; for SY type it is recommended to follow current guidelines; and for SE type it is advisable to skip dual therapy and start the triple therapy early. Finally, the therapeutic response to OHAs is different among Korean T2DM patients with different Sasang constitutional types. Taken together, the choice of effective OHAs therapy for each type is necessary in order to minimize the poor control of blood glucose level, the risk of complications, and the costs from a failure of therapy.

• Journal of Microbiology
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• 제43권3호
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• pp.313-318
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• 2005

In this study, we demonstrate the use of a PCR-based method for the detection of the specific genes involved in natural-product biosynthesis. This method was applied, using specifically designed PCR primers, to the amplification of a gene segment encoding for sedo-heptulose 7-phosphate cyclase, which appears to be involved in the biosynthetic pathways of $C_7N$ aminoacyclitol or its keto analogue-containing metabolites, in a variety of actinomycetes species. The sequences of DNA fragments (about 540 bp) obtained from three out of 39 actinomycete strains exhibited a high degree of homology with the sedo-heptulose 7-phosphate cyclase gene, which has been implicated in acarbose biosynthesis. The selective cultivation conditions of this experiment induced the expression of these loci, indicating that the range of $C_7N$ aminoacyclitol or its keto analogue-group natural products might be far greater than was previously imagined. Considering that a total of approximately 20 $C_7N$ aminoacyclitol metabolites, or its keto analogue-containing metabolites, have been described to date, it appears likely that some of the unknown loci described herein might constitute new classes of $C_7N$ aminoacyclitol, or of its keto analogue-containing metabolites. As these metabolites, some of which contain valienamine, are among the most potent antidiabetic agents thus far discovered, the molecular detection of specific metabolite-producing actinomycetes may prove a crucial step in current attempts to expand the scope and diversity of natural-product discovery.

• Journal of Microbiology and Biotechnology
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• 제18권1호
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• pp.110-117
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• 2008

Three kinds of prenylated flavonols, icariside I, icariside II, and icaritin, were isolated from an icariin hydrolysate and their effects on melanogenesis evaluated based on mushroom tyrosinase inhibition and quantifying the melanin contents in melanocytes. Although none of the compounds had an effect on tyrosinase activity, icariside II and icaritin both effectively inhibited the melanin contents with an $IC_{50}$ of 10.53 and $11.13{\mu}M$, respectively. Whereas icariside II was obtained from a reaction with ${\beta}$-glucosidase and cellulase, the icariin was not completely converted into icariside II. Thus, for the high-purity production of icariside II, the reaction was optimized using the response surface methodology, where an enzyme concentration of 5.0mg/ml, pH 7, $37.5^{\circ}C$, and 8 h reaction time were selected as the central conditions for the central composite design (CCD) for the enzymatic hydrolysis of icariin into icariside II using cellulase. Empirical models were developed to describe the relationships between the operating factors and the response (icariside II yield). A statistical analysis indicated that all four factors had a significant effect (p<0.01) on the icariside II production. The coefficient of determination $(R^2)$ was good for the model (0.9853), and the optimum production conditions for icariside II was an enzyme concentration of 7.5mg/ml, pH 5, $50^{\circ}C$, and 12 h reaction time. A good agreement between the predicted and experimental data under the designed optimal conditions confirmed the usefulness of the model. A laboratory pilot scale was also successful.

• Journal of Applied Biological Chemistry
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• 제58권4호
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• pp.317-323
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• 2015

산딸나무 열매로부터 phenolic compounds를 추출 후 생리활성을 검정하여 기능성 소재로 활용가능성을 살펴보았다. 산딸나무 열매에 함유된 페놀성 물질은 물과 40% ethanol을 용매로 하여 추출하였을 때 각각 7.04, 4.47 mg/g 함량을 나타내었다. 추출물의 phenolic 농도를 $50-200{\mu}g/mL$로 조절하여 1,1-diphenyl-2-picrylhydrazyl를 측정한 결과, 물 추출물과 ethanol 추출물 $50{\mu}g/mL$ phenolics 농도에서 각각 84, 86%였고, 2,2'-Azinobis-(3-ethylbenzothiazoline-6-sulfonic acid radical decolorization은 $100{\mu}g/mL$ phenolics 농도의 물 추출물과 ethanol 추출물에서 각각 84%, 95%였다. Antioxidant protection factor는 $50{\mu}g/mL$ phenolics 농도에서 물 추출물과 ethanol 추출물에서 각각 1.93와 1.82 PF로 측정되었으며, TBARs값은 $150{\mu}g/mL$ phenolics 농도에서 물 추출물이 69%, ethanol 추출물에서 89%를 나타내었다. Xanthine oxidase 저해능은 물 추출물과 ethanol 추출물에서 각각 34, 60%로 측정되었으며, ${\alpha}$-glucosidase 저해능은 물 추출물과 ethanol 추출물에서 각각 29, 87%의 높은 효능을 보였다. Tyrosinase 저해능을 측정한 결과 ethanol 추출물에서만 19%의 효능을 나타내었다. Collagenase 저해능 측정 결과 $200{\mu}g/mL$ phenolics 농도에서 물 추출물과 ethanol 추출물이 각각 53, 77%의 높은 저해력을 나타내어 주름개선효과가 높았다. 염증억제효과로서 hyaluronidae 저해활성을 측정한 결과, $200{\mu}g/mL$ phenolic 농도의 물 추출물에서 34%의 염증억제효과를 나타내었다. 이러한 결과로 보아 산딸나무 열매추출물은 항산화, 통풍억제, 당분해 억제, 주름개선효과, 염증억제 등의 기능성 소재로서 활용이 가능할 것으로 판단되었다.

• 한국식품과학회지
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• 제49권6호
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• pp.668-675
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• 2017

본 연구에서는 눈개승마(Aruncus dioicus var. kamtschaticus)의 in vitro 산화방지활성 및 고당(intensive glucose)과 과산화수소($H_2O_2$)로 야기된 산화적 스트레스로부터의 뇌신경세포 손상에 대한 보호효과와 더불어 알파글루코사이드가수분해효소 및 아세틸콜린에스터가수분해효소 억제효과를 확인하였으며 또한 HPLC를 이용하여 주요 물질을 분석하였다. 눈개승마 아세트산에틸 분획물(ethylacetate fraction from Aruncus dioicus var. kamtschaticus: EFAD)은 매우 우수한 총 페놀화합물 함량(430.08 mg GAE/g)과 총 플라보노이드 함량(511.72 mg RE/g)을 나타냈으며, 높은 ABTS 라디칼 소거 활성과 과산화지방질생성물의 억제력을 확인하였다. 또한 고당(intensive glucose)과 과산화수소($H_2O_2$)로 야기된 뇌신경세포에서의 산화적 스트레스 및 이로 인한 뇌신경세포 사멸을 측정한 결과, 눈개승마 아세트산에틸 분획물(EFAD)의 유의적인 뇌신경세포 보호효과를 확인할 수 있었다. 추가적으로 다당류 분해 효소인 알파글루코사이드가수분해효소 억제효과 및 아세틸콜린 분해 효소인 아세틸콜린에스터가수분해효소 억제효과를 살펴봄으로써 혈당 상승 억제효과와 뇌신경전달물질의 세포 내 유지 효과를 확인하였다. 마지막으로 눈개승마 아세트산에틸 분획물(EFAD)의 주요 페놀성 물질을 확인하기 위해 HPLC분석을 한 결과 카페산으로 추정되었다. 본 연구 결과들을 고려할 때, 눈개승마는 고혈당 지연 또는 개선을 통한 고혈당 예방 소재로서의 가능성뿐만 아니라 이로 인해 야기되는 산화적 스트레스로부터 뇌신경 세포를 보호함으로써 고혈당에 의한 대사성 뇌신경질환 예방 소재로도 활용 가능성이 있을 것이라 판단된다.

• 한국식품영양과학회지
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• 제37권4호
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• pp.452-458
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• 2008

당뇨 환자를 위한 기존의 뽕잎 건강식품의 기능을 보완할 목적으로 뽕잎분말과 DNJ 생산균주인 Bacillus subtilis MORI균의 대두발효 혼합물을 신생 당뇨유도쥐에 4주간 경구투여 하여 먹이섭취량, 체중변화, 혈당량, 내당능, 혈중 지질함량, 장기무게 등을 조사하였다. 전체적으로 당뇨유도 시험군은 정상시험군(NC군)과 비교하여 사료섭취량은 많았으나 증체량이 적어 낮은 사료효율을 보였다. 그러나 뽕잎(M군) 및 뽕잎함유대두발효물(MM군)의 투여에 의해 사료효율이 개선되었으며 특히 MM-60군에서 가장 높은 사료효율을 나타내었다. 1주일 간격으로 4주간에 걸쳐 시행한 혈당량 측정 결과 뽕잎이나 뽕잎함유대두발효물의 투여는 공복혈당을 크게 감소시켰으며 특히 MM-60군과 MM-120군은 당뇨대조군(DC군)에 비해 유의적으로 낮게 나타났다. 4주간의 시료투여 후 경구당부하시험에 의한 내당능 조사 결과 뽕잎투여나 뽕잎함유대두발효물의 투여는 혈당량을 꾸준히 감소시켰으며 특히 포도당 투여 후 120분에서의 MM-60군과 MM-120군은 DC군에 비해 유의적으로 낮은 혈당량을 보여 뽕잎 단독보다는 대두발효배양물 첨가에 의해 내당능이 크게 개선된 것으로 나타났다. 혈중 총콜레스테롤 및 중성지질 역시 DC군에서 높은 함량을 나타냈으나 뽕잎이나 뽕잎함유대두발효물 투여에 의해 지질함량이 감소하였으며 그 감량 정도는 총콜레스테롤에서는 MM-60군과 MM-120군에서 그리고 중성지질의 경우에는 M군, MM-60군, MM-120군에서 DC군에 비해 유의적인 감소를 나타내었다. 당뇨 유발에 의해 쥐의 간, 신장, 비장, 심장 등 체내 주요장기의 무게는 크게 증가하였으나 뽕잎 또는 뽕잎함유대두 발효물 투여에 의해 이들 장기의 무게는 대부분 감소하였으며 특히 MM-60군, MM-120군은 DC군에 비해 유의적인 감소를 나타내었다. 이상의 실험결과 뽕잎분말과 DNJ 생산 균주인 B. subtilis MORI균의 대두발효물의 혼합물은 신생 당뇨유도쥐의 제반 당뇨증세 완화에 긍정적으로 작용하는 것이 확인되었으며 따라서 뽕잎함유대두발효물은 앞으로 당뇨환자들에 대한 건강식품 소재로 그 활용이 크게 기대된다 하겠다.

• Nutrition Research and Practice
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• 제5권5호
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• pp.435-442
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• 2011

At present, lifestyle-related diseases are one of the most critical health issues worldwide. It has been reported that lipopolysaccharide derived from a Gram-negative bacteria (IP-PA1) symbiotic with wheat exhibited several advantageous biological effects, such as the reduction of plasma glucose levels in NOD mice and low-density lipoprotein (LDL) levels in WHHL rabbits. In this study, the beneficial effects on plasma glucose and lipids of a tea (SI tea) consisting of IP-PA1 and Salacia (which contains an inhibitor of ${\alpha}$-glucosidase) were investigated in the KK-Ay/TaJcl type 2 diabetic model mice and in human subjects with premetabolic syndrome in a double-blind, randomized study. S1 tea significantly decreased plasma glucose levels in KK-Ay/TaJcl mice. A clinical trial of SI tea was performed with 41 subjects between the ages of 40 and 69, who belonged either to a high plasma glucose group (HG: FPG 100-125 mg/dl) or to a hyperlipidemia group (HL: TG ${\geq}$ 150 mg/dl, or LDL ${\geq}$ 120 mg/dl, or HDL <40 mg/dl). These subjects ingested either Salacia without IP-PA1 (the control) or SI tea. Blood samples were collected at 0, 30, and 60 days after initiating SI tea treatment, and were measured for FPG, HbA1c, TG, LDL, and HDL. These results showed that SI tea reduced FPG and HbA1c more rapidly than the control in the HL group, and also significantly improved LDL and HDL levels in the HG group. Thus, SI tea may be helpful in preventing lifestyle-related diseases.