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1 Microbiol. Biotechnol. Lett. (2015), 43(2), pissn X eissn Microbiology and Biotechnology Letters Rhizopus oryzae KSD-815 를이용하여제조된 R4 누룩의항혈전활성 김미선 1, 이예슬 1, 김종식 2, 신우창 3, 손호용 1 * 1 안동대학교식품영양학과 2 안동대학교생명과학과 3 ( 주 ) 국순당 Received: February 12, 2015 / Revised: March 10, 2015 / Accepted: March 25, 2015 In-vitro Anti-thrombosis Activity of R4-Nuruk Made from Rhizopus oryzae KSD-815 Mi-Sun Kim 1, Ye-Seul Lee 1, Jong Sik Kim 2, Woo-Chang Shin 3, and Ho-Yong Sohn 1 * 1 Department of Food and Nutrition, and 2 Department of Life Science, Andong National University, Andong , Republic of Korea 3 Research Institute, Kooksoondang Brewery Co. Ltd., Seongnam , Republic of Korea Nuruk has been used as fermentation starter in the alcohol industry for some time in Korea. Various bioactivities, such as antiproliferative and anti-obesity, of R4 nuruk made from Rhizopus oryzae KSD-815 have been previously reported. In this study, the hot water and ethanol extract of R4 nuruk and their subsequent organic solvent fractions were prepared, and their antithrombosis activities were evaluated. The ethylacetate fraction showed strong anti-coagulation activity, and the ethylacetate and butanol fraction from hot water extract demonstrated platelet aggregation inhibitory activity, without hemolysis against human RBC. Our results suggest that R4 nuruk has the potential to act as a new anti-thrombosis agent. Keywords: Anti-coagulation, anti-platelet aggregation, Rhizopus oryzae KSD-815, R4 nuruk 술은알코올성분이있어사람을취하게하는음료를말하며, 각각의나라마다민족의공감성과문화성이깃든고유의술을가지고있다 [16]. 그예로서, 프랑스의와인, 러시아의보드카, 네덜란드의진, 일본의사케등이있으며, 우리나라에는고유의전통주로막걸리가있다. 우리나라의막걸리는찹쌀혹은멥쌀을주원료로하여누룩을발효제로사용하여제조하며, 다양한약용및식용부재료를첨가하여우리만의고유한방법으로양조하고있다. 특히누룩은전세계적으로도독특한우리만의발효제이며, 전분의당화효소로서의역할뿐만아니라발효를진행하는곰팡이, 효모, 유산균의접종원이라는측면에서중요하다 [16]. 실제전통주는사용누룩에따라술의맛, 향, 색이변화되므로누룩은전통주품질에가장중요한인자라고할수있다 [2, 20]. 통상전통누룩은소맥, 보리, 옥수수, 쌀, 귀리, 호밀과같은원료 *Corresponding author Tel: , Fax: hysohn@anu.ac.kr 2015, The Korean Society for Microbiology and Biotechnology 전분질을빻은다음, 물을뿌린후성형하여수일간미생물을배양하는방식으로제조된다 [20]. 누룩미생물로는 Rhizopus sp., Aspergillus sp., Absidia sp., Mucor sp., Penicillium sp., Endomyces sp. 등의곰팡이 [2] 와 Sacchromyces sp. 의효모 [16] 및 Leconostoc sp., Weissella sp., Pediococcus sp., Lactobacillus sp. [3, 20] 등의유산균이알려져있다. 따라서전통누룩은여러종류의미생물이혼재하여다양한특성의누룩을제조할수있다는장점은있으나, 잡균오염, 이상발효, 관능성저하및균일품질유지의어려움등의문제점을가진다 [2, 3, 20]. 따라서, 최근에는전통누룩을저온살균하여오염균을제거하여사용하거나 [19], 증자처리한소맥, 보리, 쌀등의전분질에선별된단일또는수종의미생물을접종한후수일간배양하여특정미생물이대량번식된상태의개량누룩을주로제조하여사용하고있다 [16, 20]. 본연구팀에서는전통주및주박의항비만 [16], 항산화 [16], 항염증 [21], 항혈전 [7, 8], 항세균 [7], 암세포생육억제 [5], 미백및주름개선활성 [17, 18] 등의생리활성을보고한바있으며, 이러한유용생리활성들이발효원료및발효작용에 June 2015 Vol. 43 No. 2

2 170 Kim et al. 기인할뿐만아니라, 누룩그자체에의해서도나타나는것으로추측하고있다 [9, 16-18]. 실제 Rhizopus oryzae KSD- 815 (Rhizopus sp. KFCC 1279) 로제조된개량누룩 (R4로명명 ) 의경우, 누룩추출물의지방산화합물의암세포생육억제활성 [11, 14], sterol 화합물의암세포전이억제활성 [12], 추출물의항비만활성 [15], 고혈압및암세포전이억제활성 [13] 등이알려져있고, 최근이화누룩의경우에도강력한항혈전활성을확인한바있다 [9]. 따라서본연구에서는 R4 의유용생리활성발굴연구의일환으로 R4 누룩의항혈전활성을평가하고자하였다. 실험에사용한 R4 누룩은 2013년상업적시설 ( 국순당, 성남, 한국 ) 에서대량제조된누룩으로, ethanol 추출물은누룩무게에대해 10배의 95% ethanol (Daejung Chemicals & Metals Co., Ltd. Korea) 을가한후상온에서 24시간, 3회반복추출하였으며, 추출액은 filter paper (Whatsman No. 2) 로거른후감압농축 (Eyela Rotary evaporator N-1000, Tokyo Rikakikai Co., Ltd. Japan) 하여조제하였다. 열수추출물은누룩무게의 10배의물을가한후 100 o C에서 2시간, 3회반복추출하였으며, 상기와동일하게감압농축및동결건조 (Ilshin Lab Co. Ltd, Yangju, Korea) 하여조제하였다. 이후, 조제된분말은증류수에현탁한후, hexane, ethylacetate, butanol로순차적분획하였으며, 최종적으로물잔류물을회수하였다. R4 누룩의 ethanol 및열수추출의수득율, 다양한용매에대한분획수득율및성분분석결과는 Table 1에나타내었다. Ethanol 추출물의수득율은 6.2% 이었으며, 순차적분획시 ethanol 추출물의 20.9% 및 25.6% 는 hexane 및 butanol 분획으로, 50.4% 는물잔류물로이행되었으며, ethylacetate 분획물은 ethanol 추출물의 2.6% 를차지하였다. 이러한결과는 R4 누룩 100 g 에대해 ethylacetate 분획물약 0.16 g을얻게됨을의미한 다. 한편열수추출물의수득율은 20.2% 로 ethanol 추출에비해 3.26 배높았으며, hexane, ethylacetate, butanol 분획은추출물의 0.1%, 0.8%, 9.1% 로미미하게나타났으며, 대부분 (90.9%) 은물잔류물로분획되었다. 따라서열수추출물의대부분은수용성당류로추측된다. 조제된 R4 누룩 ethanol 추출물의총폴리페놀 (total polyphenol: TP) 및총플라보노이드 (total flavonoid: TF) 함량을측정한결과 (Table 1), 쌀을주재료로하는이화누룩보다는높은함량의 27.3 mg/g 의 TP 및 1.5 mg/g 의 TF 함량을나타내었으며 [9], 분획물의경우 ethylacetate 분획에서 mg/g 의매우높은 TP 및 2.9 mg/g 의높은 TF 함량을나타내었다. R4 누룩열수추출물은 ethanol 추출물보다높은 16.5 mg/g 의 TP 및 2.2 mg/ g 의 TF 함량을나타내었으며 (Table 1), 분획물의경우 ethylacetate 분획에서 mg/g 및 15.3 mg/g 의가장높은 TP 및 TF 함량을나타내었다. 이때 TP 및 TF 함량은기존보고 [23, 25] 와동일하게 tannic acid 및 rutin 을표준시약으로사용하였다. R4 누룩추출물및분획물의항혈전활성은혈액응고저해활성과혈소판응집저해활성을측정하여평가하였다. 혈액응고저해활성은혈액응고반응에서중추적역할을수행하는 thrombin 의활성을평가하는 thrombin time (TT), 외인성응고계 (II, V, VII 및 X 인자 ) 의응고활성을종합적으로측정하는 prothrombin time (PT) 및내인성경로에의한혈액응고활성을평가하는 activated partial thromboplastin time (aptt) 을측정하였다 [1, 8, 9]. 각각의측정은기존의보고 [8] 와동일하게실시하였으며, 시료대조군으로는아스피린 (Sigma Co., St. Louis, MO, USA) 을용매대조군으로는 DMSO 를사용하였으며, TT, PT 및 aptt 연장활성은각각 3 회이상반복한시료실험의평균치를용매대조구인 DMSO Table 1. Yields of extraction and subsequent organic solvent fractions of R4-nuruk made from Rhizopus oryzae KSD-815 and their total polyphenol and total flavonoid contents. Extraction Extraction/Fraction yield Content (mg/g) Extract/Fraction Solvent (%) Total polyphenol Total flavonoid Ethanol Ethanol ex. 1) ± 0.6 1) 01.5 ± 0.0 Hexane fr. 2) ± ± 0.0 Ethylacetate fr ± ± 0.5 Butanol fr ± ± 0.1 Water residue ± ± 0.1 Hot water Hot water ex ± ± 0.2 Hexane fr ± ± 0.6 Ethylacetate fr ± ± 2.2 Butanol fr ± ± 0.9 Water residue ± ± 0.0 1) ex: extract, 2) fr.: fraction. Data are presented as the mean ± SD of three determinations.

3 Biological Activity of Korea Traditional Nuruk 171 의실험평균치의비로나타내었다 [6-9]. 실험결과는 SPSS 21.0 버전을사용하여 mean ± SD 로나타내었으며, 각군간의차이는 ANOVA 로분석하였으며, Duncan 다중비교검증법으로통계적유의성검정을조사하였다. 유의수준은 p <0.05 로하였다. 혈액응고저해활성분석결과, 대조구로사용된 aspirin (1.5 mg/ml) 은 TT, PT, aptt 를무첨가구에비해각각 1.7 배연장시켜우수한항혈전효과를확인하였다. 한편 R4 누룩의 ethanol 및열수추출물 (5 mg/ml) 은 TT 에서약한연장활성이나타났으나, PT 및 aptt 의변화는나타나지않았다 (Table 2). 그러나 ethanol 추출물의순차적분획물에서는다양한혈액응고저해활성이나타났으며, ethylacetate 분획에서는대조구에비해각각 2.0 배, 2.6 배, 1.9 배연장된 TT, PT, aptt 를나타내었으며, 농도의존적인저해활성과함께 7 mg/ml 농도에서는대조구에비해각각 4.5 배, 5.1 배, 15 배연장된 TT, PT, aptt 를나타내어내인성경로에의한혈액응고인자저해가매우강력함을확인하였다 (Table 2). 열수추출물의경우 ethylacetate 분획에서 1.5 배연장된 TT 를나타내었으나, ethanol 추출물의분획물보다낮은활성을나타내었다. 이는열수추출동안의활성물질의손실및실활에기인하는것으로판단되며, 실제 ethanol 추출물의 ethylacetate 분획물을 100 o C 에서 1 시간열처리이후잔존활성을평가한결과열처리전과비교하여 60% 정도의 aptt 활성을나타냄을확인하였다. 상기의결 과는, 항혈전활성물질회수를위해서는 ethanol 추출이적합하며, R4 누룩의 ethylacetate 분획은기존한방자원 [6] 보다우수하며, 강력한혈액응고인자저해활성이알려진흑마늘의 ethylacetate 분획과유사하였다 [4]. R4 누룩의항혈전활성평가를위해혈소판응집저해활성을평가하였으며, 그결과는 Table 3에나타내었다. 혈소판은내피세포의손상으로노출된 collagen 등과결합하여혈전생성을개시하는중요한세포 [1] 로, 혈소판의비정상적인응집은혈전생성을촉진시켜정상적인혈액순환을저해한다. 본연구에서의혈소판응집저해활성은미세전극에혈소판이부착되어응집됨에따라발생하는전기저항값의변화를측정하는 impedance 법을사용하여평가하였다 [24]. 인간농축혈소판 (platelet rich plasma: PRP) 은적십자로부터공급받았으며 PRP의전처리및수세과정은기존의보고 [18] 와동일하게하였으며, 최종혈소판농도가 /ml이되도록조정한후, Whole Blood Aggregometer (Chrono-log, PA, USA) 를사용해 37 o C에서측정하였으며, 10 mm CaCl 2 50 µl, suspending buffer µl, 시료 5 µl가포함된반응 cuvette에혈소판 50 µl을넣은후 3분동안 37 o C로가온후응집유도제로 collagen (1 mg/ml) 을 2.5 µl를넣고혈소판응집을측정하였다. 응집반응은 collagen 첨가후 12분간측정하였으며 amplitude, slope, area under를측정하여평가하였다 [18]. 이때, amplitude (ohm) 는혈소판에응집유도제 Table 2. Effect of the ethanol and hot water extracts of R4-nuruk made from Rhizopus oryzae KSD-815 and their solvent fractions on blood coagulation. Extraction Chemicals/Extract Concentration Anti-thrombosis activity 1) Solvent /Fraction (mg/ml) TT PT aptt - DMSO - 1.0± 0.0 a 1.0 ± 0.0 a 1.0 ± 0.1 a - Aspirin ± 0.0 e 1.7 ± 0.0 c 1.7 ± 0.0 c Ethanol Ethanol ex. 2) ± 0.1 b 1.0 ± 0.0 a 1.0 ± 0.1 a Hexane fr. 3) ± 0.0 b 1.3 ± 0.1 b 1.6 ± 0.0 b Ethylacetate fr ± 0.0 f 2.6 ± 0.2 d 1.9 ± 0.1 d ± ± ± ± ± 0.1 >15.0 Butanol fr ± 0.0 b 1.1 ± 0.0 a 1.0 ± 0.1 a Water residue ± 0.0 a 1.0 ± 0.0 a 1.0 ± 0.0 a Hot water Hot water ex ± 0.1 b 1.0 ± 0.0 a 1.0 ± 0.0 a Hexane fr ± 0.0 a 1.0 ± 0.0 a 1.0 ± 0.0 a Ethylacetate fr ± 0.0 d 1.0 ± 0.0 a 1.1 ± 0.1 a Butanol fr ± 0.1 c 1.0 ± 0.0 a 1.0 ± 0.0 a Water residue ± 0.0 b 1.0 ± 0.0 a 1.0 ± 0.0 a 1) Anti-thrombosis activity: Data are presented as relative clotting time based on solvent control. The thrombin time (TT), prothrombin time (PT) and activated partial thromboplastin time (aptt) of solvent control (dimethylsulfoximide) were 26.7 sec, 18.8 sec and 40.1 sec, respectively. 2) ex: extract, 3) fr.: fraction. Different superscript letters (a-f) within a column differ significantly (p < 0.05). June 2015 Vol. 43 No. 2

4 172 Kim et al. Table 3. Platelet aggregation activities of the ethanol and hot water extract and their solvent fractions of R4-nuruk made from Rhizopus oryzae KSD-815. Extraction Solvent Chemicals/Extract /Fraction Amplitude (Ω) Slope (Ω/min) Lag time (sec) Area under - DMSO Aspirin (0.5 mg/ml) Aspirin (0.25 mg/ml) Ethanol Ethanol ex. 2) Hexane fr. 3) Ethylacetate fr Butanol fr Water residue Hot water Hot water ex Hexane fr Ethylacetate fr Butanol fr Water residue ) PAR: Platelet Aggregation Ratio, 2) ex: extract, 3) fr.: fraction. The concentrations of samples of R4-nuruk used were 0.25 mg/ml, respectively. Data are presented as a representative result relative of independent three determinations. Amplitude is expressed as ohms by maximum extent of platelet aggregation, and slope (rate of reaction) is determined by drawing a tangent through the steepest part of curve. Area under is a calculated area in descent drawing during platelet aggregation. PAR 1) (%) 를첨가하였을때일어나는최대응집정도를나타내며, slope 는응집유도제를첨가한직후부터 1 분동안의응집곡선의기울기를나타내며, area under 는전체적인혈소판응집정도를표시하는것으로전기저항증가에따른 slope 곡선의하강면적을나타낸다 [18]. R4 누룩의혈소판응집저해활성은시료대신 DMSO 를첨가한대조구와의상대적인 area under 값의비를백분율로나타내었다. 대조구로사용된혈소판응집저해제인아스피린은농도의존적인혈소판응집저해활성을나타내었으며, 0.25 mg/ml 농도에서무첨가구에비해 65.9% 의응집율을나타내었다 (Table 3). R4 누룩의 ethanol 추출물및분획물 (0.25 mg/ml) 은, butanol 분획물을제외한모든시료에서유의적인혈소판응집저해활성은나타나지않았으며, 오히려응집촉진이나타났다. 한편 R4 누룩의열수추출물및분획물중에서는 ethylacetate 및 butanol 분획에서혈소판응집저해활성을나타내었다. 따라서 R4 누룩은다양한성분의혈액응고효소, 혈액응고인자및혈소판응집저해활성물질을포함하고있음을확인하였다. 한편인간적혈구에대한용혈활성을평가하였으며, 인간적혈구 (4%) 100 µl 를 96-well microplate 에가하고다양한농도의시료용액 100 µl 를가한다음 37 o C 에서 30 분간반응시켰으며, 이후, 반응액을 10 분간원심분리 (1,500 rpm) 하여상등액 100 µl 를새로운 microtiter plate 로옮긴후용혈에따른헤모글로빈유출정도를 414 nm 에서측정하여평가하였 Table 4. Hemolytic activities of the ethanol and hot water extract and their solvent fractions of R4-nuruk made from Rhizopus oryzae KSD-815 against human red blood cell. Samples/Chemicals (mg/ml) Hemolysis against human RBC (%) DMSO 0.0 ± 0.6 Triton X-100 (0.1%) 99.9 ± 0.5 Ethanol extract (0.5) Extract 23.0 ± 0.4 Hexane fr. 1) 91.4 ± 0.5 Ethylacetate fr ± 0.2 Butanol fr ± 2.2 Water residue -0.7 ± 0.5 Hot-water extract (0.5) Extract 2.3 ± 0.8 Hexane fr. 1.4 ± 0.7 Ethylacetate fr. 0.8 ± 1.0 Butanol fr. 5.5 ± 0.7 Water residue 0.8 ± 0.1 1) fr: fraction. 다 [10]. 그결과, ethanol 추출물 (0.5 mg/ml) 에서 23% 이상의용혈활성이나타났으며, 특히 hexane 및 ethylacetate 분획물에서는용혈활성이강하게나타났다 (Table 4). 본연구결과는 R4 열수추출물의 ethylacetate 분획은향후항응고

5 Biological Activity of Korea Traditional Nuruk 173 및혈소판응집저해개발의유용자원으로이용가능함을제시하고있다. 향후 R4 누룩으로부터활성물질의정제및이의항혈전기작연구가필요하다고판단된다. 요 약 누룩은전세계적으로도독특한우리만의발효제로, 전분당화및발효미생물의접종원으로이용된다. Rhizopus oryzae KSD-815 로제조된개량누룩 (R4 로명명 ) 은발효제특성이외에암세포생육억제, 항비만활성등이알려져있다. 본연구에서는 R4 누룩의열수및 ethanol 추출물과이들의순차적유기용매분획물을조제하여항혈전활성을평가한결과, ethylacetate 분획에서우수한항응고활성을확인하였으며, 열수추출물의 ethylacetate 및 butanol 분획은인간적혈구용혈활성을나타내지않으면서혈소판응집저해활성을나타내었다. 본연구결과는 R4 누룩이항응고및혈소판응집저해개발의유용자원으로이용가능함을제시하고있다. Acknowledgments This research was supported by High Value-added Food Technology Development Program (No ), Ministry for Food, Agriculture, Forestry and Fisheries, Republic of Korea. References 1. Chen H, Qi X, He C, Yin Z, Fan D, Han G Coagulation imbalance may not contribute to the development of portal vein thrombosis in patients with cirrhosis. Thrombosis Res. 131: Huh CK, Kim SM, Kim YD Comparison for enzymatic activity of nuruk and quality properties of yakju by different fungi. Korean J. Food Preserv. 21: Jang D, Park S, Lee H, Pyo S, Lee HS Isolation of alcohol-tolerant lactic acid bacteria Pediococcus acidolactici K3 and S1 and their physiological characterization. Korean J. Microbiol. Biotechnol. 41: Jung IC, Sohn HY Antioxidation, antimicrobial and antithrombosis activities of aged black garlic (Allium sativum L.). Korean J. Microbiol. Biotechnol. 42: Kang HT, Lee SH, Kim SY, Kim MS, Shin WC, Sohn HY, et al Anti-proliferative activities of solvent fractions of lees extract in human colorectal HCT116 cells. J. Life Sci. 24: Kim JI, Jang HS, Kim JS, Sohn HY Evaluation of antimicrobial, antithrombin, and antioxidant activity of Dioscorea batatas Decne. Korean J. Microbiol. Biotechnol. 37: Kim MS, Lee YS, Kim JS, Shin WC, Sohn HY Antimicrobial and anti-thrombosis activities of lees of sweet potato soju. Korean J. Microbiol. Biotechnol. 42: Kim MS, Lee YS, Kim JS, Shin WC, Sohn HY Evaluation of in-vitro antithrombosis activity of lees of Korean traditional wine. J. Life Sci. 24: Kim MS, Lee YS, Kim JS, Shin WC, Sohn HY In-vitro antithrombosis activity of Ehwa nuruk. Korean J. Microbiol. Biotechnol. 42: Kim MS, Sohn HY Anti-thrombosis activity of the aerial parts of Aruncus dioicus var kamtschaticus. J. Life Sci. 24: Kwak HY, Lee SJ, Lee DY, Jung L, Bae NH, Hong SY, et al Cytotoxic and anti-inflammatory activities of lipids from the nuruk (Rhizopus oryzae KSD-815). J. Korean Soc. Appl. Biol. Chem. 51: Lee DY, Lee SJ, Kwak HY, Jung L, Heo J, Hong SY, et al Sterols isolated from Nuruk (Rhizopus oryzae KSD- 815) inhibit the migration of cancer cells. J. Microbiol. Biotechnol. 19: Lee SJ, Bae HJ, Ryu JY, Lee DY, Kim GW, Baek NI, et al Extracts from Rhizopus oryzae KSD-815 of Korean traditional nuruk confer the potential to inhibit hypertension, platelet aggregation, and cancer metastasis in vitro. Food Sci. Biotechnol. 18: Lee SJ, Hong SY, Kim GW γ-linolenic acid methyl ester from Rhizopus oryzae KSD-815 isolated from nuruk induced apoptosis in prostate cancer LNCaP cells. J. Korean Soc. Appl. Biol. Chem. 53: Lee SJ, Kim GW Hypolipidemic effect of hexane fraction from Rhizopus oryzae KSD-815 through peroxisome proliferator-activated receptor-α. J. Korean Soc. Appl. Biol. Chem. 53: Lee SJ, Kim JH, Jung YW, Park SY, Shin WC, Park CS, et al Composition of organic acids and physiological functionality of commercial makgeolli. Korean J. Food Sci. Technol. 43: Lee SJ, Kwon YY, Cho SW, Kwon HS, Shin WC Effect of ehwa makgeolli containing oriental herbs on skin whitening and wrinkles. J. Korean Soc. Food Sci. Nutr. 42: Lee SM, Lee SJ, Kwon YY, Baek SH, Kim JS, Sohn HY, et al Skin whitening and anti-wrinkle effects of extract from Jubak of oriental herbal liquor. J. Korean Soc. Food Sci. Nutr. 43: Park JH, Choi JH, Yeo SH, Teong ST, Cho HA, Kang JE, et al A study on the quality characteristics of makgeolli using heat treatment of traditional Korean nuruk extract. J. East Asian Soc. Dietary Life 23: Park JH, Chung CH Characteristics of takju (a cloudy Korean rice wine) prepared with nuruk (a traditional Korean rice wine fermentation starter), and identification of lactic acid bacteria in nuruk. Korean J. Food Sci. Technol. 46: Park MJ, Kang HT, Kim MS, Shin WC, Sohn HY, Kim JS Anti-inflammatory effects of extracts and their solvent June 2015 Vol. 43 No. 2

6 174 Kim et al. fractions of rice wine lees. J. Life Sci. 24: Shin MO, Kang DY, Kim MH, Bae SJ Effect of growth inhibition and quinone reductase activity stimulation of makgeoly fractions in various cancer cells. J. Korean Soc. Food Sci. Nutr. 37: Singleton VL, Orthofer R, Lamuela-Raventos RM Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin-Ciocaleau reagent. Methods Enzymol. 299: Sweeney JD, Hoerning LA, Behrens AN, Novak E, Swank RT Thrombocytopenia after desmopressin but absence of in-vitro hypersensitivity to ristocetin. Am. J. Clin. Path. 93: Valentina U, Fabcic J, Stampar F Sugars, organic acids, phenolic composition and antioxidant activity of sweet cherry (Prunus avium L.). Food Chem. 107:

DBPIA-NURIMEDIA

DBPIA-NURIMEDIA J East Asian Soc Diet Life 27(3): 348 363 (2017) http://dx.doi.org/10.17495/easdl.2017.6.27.3.348 348 1 1 2 1 1, 2 Mixed Culture Characteristics of Fungi Strains isolated from Korean Traditional Nuruk