微生物发酵提高蚕桑生物质DNJ的优化条件研究
|
摘要
1-脱氧野尻霉素(1-deoxynojirimycin,DNJ)是一种多羟基哌啶生物碱,因其结构类似单糖也称为亚胺基糖。DNJ具有多种生物活性,如降血糖、抗病毒、抗肿瘤等,在食品、医药等领域具有重要的应用价值而倍受关注。桑树中含有丰富的DNJ,其DNJ的含量已经作为判断蚕桑生物质降血糖等效果的重要指标之一。本研究以高效提取蚕桑生物质DNJ和通过发酵法提高其含量为出发点,探讨响应面法优化蚕粉DNJ稀酸浸提工艺、筛选出能大幅度提高蚕桑生物质DNJ的发酵菌种并对发酵条件进行优化、研究优势微生物菌种发酵蚕桑生物质DNJ产量的应用前景,以期为蚕桑资源的精深加工和DNJ产品的开发利用提供理论和技术指导。主要取得如下研究结果。
采用响应面法优化出稀酸浸提家蚕DNJ的数学模型为:Y= 0.47+ 0.054X_1 - 0.03X_2- 0.00925X_3+ 0.03X_1X_2- 0.07X_1X_3- 0.059X_2X_3- 0.013X_1~2 - 0.027X_2~2 + 0.024X_3~2 ,该模型显著,能够解释各因素对家蚕DNJ提取效果的影响。通过响应面法优化出稀酸浸提家蚕DNJ的最佳工艺参数为:提取时间3.3h,浸提温度72.9℃,料液比分数为1:282。在此模型影响的稀酸浸提DNJ的理论提取率为0.493%,实际提取率为0.487%,理论值和实际值基本一致。模型的响应面和等高线分析发现,浸提时间、浸提温度和料液比分数之间存在明显的交互作用。
本文通过比较8种起始发酵菌株,筛选出灵芝菌种为发酵桑叶DNJ产量的最合适菌种。经PB设计,在比较8个不同因素对灵芝菌种发酵桑叶产DNJ的实际影响分析得出,微环境pH值,无机氮源KNO3含量和菌体接种量作用明显。进一步的单因素分析,并结合采用响应面法优化出的灵芝菌种发酵条件数学模型为:Y=0.054-9.37×10-4X1+1.25×10-5X2+5×10-5X3-9.75×10-4X1X2+1.5×10-4X1X3+6.5×10-4X2X3-7.32×10-3X 12 -9.27×10-3X 22 -7.25×10-3X 32 ,该模型显著,能够解释各因素对桑叶DNJ提取效果的影响。通过响应面法优化出灵芝菌种发酵桑叶DNJ的最佳发酵为:pH值6.97,KNO3含量0.81%,菌体添加量2.00 mL。在此模型影响的灵芝菌发酵液DNJ提取率为0.548%,与发酵前比较,经灵芝菌种发酵后DNJ含量大幅度提高。模型的响应面和等高线分析显示,pH值、KNO3含量和菌体添加量之间交互作用明显,进一步验证模型可靠。
在比较桑树不同部位DNJ含量发现:桑叶DNJ的分布规律为:上位叶>侧根>中位叶≥桑枝皮>下位叶,由此可见桑嫩叶可能是DNJ的主要来源生产部位;比较蚕粉不同干燥工艺得出:超低温冷冻干燥>喷雾干燥>热风干燥,显示出超低温冷冻干燥有利于保持生物活性物质DNJ分子结构特性,而喷雾干燥过程中有瞬时加热的过程,通风干燥则加热时间较长,从而影响其检测量。经灵芝菌发酵后,桑叶(上位叶)DNJ含量提高20.6%;冻干燥蚕粉DNJ含量为51.2%,提高了6.9%;调查三龄第1天至五龄第7天每天蚕粪发酵前后DNJ含量的变化趋势,结果显示,发酵前后变化趋势一致;三龄第1天蚕粪DNJ含量最高,然后逐渐下降,从五龄第2天至五龄第7天趋于平缓,其中五龄第4天含量最低。发酵后蚕粪DNJ含量平均提高20%,最高为五龄第4天,提高40.8%。关于家蚕对DNJ的吸收和排泄机制有待于进一步深入研究。
1-Deoxynorijimycin (DNJ) as a kind of polyhydroxy piperidines was also called iminosugar for its configuration similar with sugar. DNJ appeared to be useful in food and medicine for its potential biological activities, such as inhibition of abnormal elevation of plasma glucose, anti-virus and anti-tumor. Therefore, DNJ had long been of interest for its suppressing the plasma glucose content with general consents. Mulberry resource enriched in DNJ, which can prohibit the bioactivities of intestinal alpha-glucosidase in vivo, and whose content in sericulture biomass was considered as one of significant indexes for effect on inhibition of postprandial glycemia. From the perspectives of extraction of DNJ from the silkworm with proficiency and elevation of DNJ content in sericulture resource by fermentation, this study focused on diluted acid extraction of DNJ from silkworm with surface response methodology (RSM), investigated a advantageous strain with fermentation conditions optimized by PB design and RSM, which could enhanced the DNJ content to a large extent from mulberry leaves, and groped for a prospect for production of DNJ from other sericulture resource fermented by the specific microorganism. Based on the results of this study, it is foreseen that production of DNJ and sericulture development of deep level would have the performance improved. Main results are as the following:
The formula of diluted acid extraction of DNJ from silkworm with RSM could expressed as Y= 0.47+ 0.054X_1 - 0.03X_2- 0.00925X_3+ 0.03X_1X_2- 0.07X_1X_3- 0.059X_2X_3- 0.013X_1~2 - 0.027X_2~2 + 0.024X_3~2 , Which was significant and could elucidate impact of extraction factors on DNJ content from silkworm. The optimal extraction conditions were defined as: 72.9℃, 3 hours for 18 minutes and 1:282 of solid to liquid. The DNJ extracted after optimization was 0.493%, while predicted value was 0.487%, reflecting the both was consent with each other. There were obvious mutual interactions among the extraction time, temperature and the ratio of material to liquid throughout Contour line plot and response surface graph of DNJ yield.
In compare with eight strains as starter cultures, Ganoderma lucidum was defined as the candidate for the fermentation by conversion of mulberry leaves into DNJ. And then analyzing eight factors effects on yield of DNJ fermented by Ganoderma lucidum by Plackett-Burman design, the range of pH, content of potassium nitrate and inoculum size was utilized for the following study, that is to say, for the single factor assay. The regression model for the optimizing the fermentation conditions was expressed as Y=0.054-9.37×10-4X1+1.25×10-5X2+5×10-5X3- 9.75×10-4X1X2+ 1.5×10-4X1X3+6.5×10-4X2X3-7.32×10-3X 12 -9.27×10-3X 22 -7.25×10-3 X 32 , Which was significantly appropriate and could elucidate impact of fermentation factors on DNJ content from mulberry. The highest amount of DNJ yield (0.548%) from the incubation broth by Ganoderma lucidum, in which fermentation broth showed better performance than origin before fermentation, would be calculated by first order local deviation with equivalence to zero, when X1, X2 and X3 received 6.97, 0.81% and 2.00 ml, respectively. There were obvious mutual interactions among the ph range, content of potassium nitrate and the inoculum size throughout Contour line plot and response surface graph of DNJ yield, suggesting the model was reliable and feasible.
The distribution of DNJ in mulberry was shown that most important independent parts were upper leaves, roots, middle leaves (equaled to cortex), bottom leaves in order by content, suggesting DNJ mostly was produced by the young leaves. In compare with three methods of drying silkworm powders, indicating that lyophilization was the best approach to deal with it, suggesting its structure would be greatly maintained by lyophilization and DNJ molecule would be degraded or denatured under hot-air involved circumstance the elevation of DNJ content fermented by microorganism from mulberry was more than from silkworm. In compare with the unfermented, the DNJ contents increased by 20.8% in mulberry and 6.9% in silkworm powder, respectively. The content of DNJ in feces before or after fermentation decreased swiftly during the 6 days, followed mildly for the rest of days till mounting, appearing to be lowest in feces on 4th day of fifth-instar larvae. And the DNJ yield in feces fermented by given microorganism was higher than one in feces primitive, 20 percent promotion in average. However, DNJ content in feces on 4th day of fifth-instar larvae advanced most, up to 40.8%. The circulation and excretion mechanism of DNJ accumulated by the larvae of Bombyx mori will be investigated for the further study.
采用响应面法优化出稀酸浸提家蚕DNJ的数学模型为:Y= 0.47+ 0.054X_1 - 0.03X_2- 0.00925X_3+ 0.03X_1X_2- 0.07X_1X_3- 0.059X_2X_3- 0.013X_1~2 - 0.027X_2~2 + 0.024X_3~2 ,该模型显著,能够解释各因素对家蚕DNJ提取效果的影响。通过响应面法优化出稀酸浸提家蚕DNJ的最佳工艺参数为:提取时间3.3h,浸提温度72.9℃,料液比分数为1:282。在此模型影响的稀酸浸提DNJ的理论提取率为0.493%,实际提取率为0.487%,理论值和实际值基本一致。模型的响应面和等高线分析发现,浸提时间、浸提温度和料液比分数之间存在明显的交互作用。
本文通过比较8种起始发酵菌株,筛选出灵芝菌种为发酵桑叶DNJ产量的最合适菌种。经PB设计,在比较8个不同因素对灵芝菌种发酵桑叶产DNJ的实际影响分析得出,微环境pH值,无机氮源KNO3含量和菌体接种量作用明显。进一步的单因素分析,并结合采用响应面法优化出的灵芝菌种发酵条件数学模型为:Y=0.054-9.37×10-4X1+1.25×10-5X2+5×10-5X3-9.75×10-4X1X2+1.5×10-4X1X3+6.5×10-4X2X3-7.32×10-3X 12 -9.27×10-3X 22 -7.25×10-3X 32 ,该模型显著,能够解释各因素对桑叶DNJ提取效果的影响。通过响应面法优化出灵芝菌种发酵桑叶DNJ的最佳发酵为:pH值6.97,KNO3含量0.81%,菌体添加量2.00 mL。在此模型影响的灵芝菌发酵液DNJ提取率为0.548%,与发酵前比较,经灵芝菌种发酵后DNJ含量大幅度提高。模型的响应面和等高线分析显示,pH值、KNO3含量和菌体添加量之间交互作用明显,进一步验证模型可靠。
在比较桑树不同部位DNJ含量发现:桑叶DNJ的分布规律为:上位叶>侧根>中位叶≥桑枝皮>下位叶,由此可见桑嫩叶可能是DNJ的主要来源生产部位;比较蚕粉不同干燥工艺得出:超低温冷冻干燥>喷雾干燥>热风干燥,显示出超低温冷冻干燥有利于保持生物活性物质DNJ分子结构特性,而喷雾干燥过程中有瞬时加热的过程,通风干燥则加热时间较长,从而影响其检测量。经灵芝菌发酵后,桑叶(上位叶)DNJ含量提高20.6%;冻干燥蚕粉DNJ含量为51.2%,提高了6.9%;调查三龄第1天至五龄第7天每天蚕粪发酵前后DNJ含量的变化趋势,结果显示,发酵前后变化趋势一致;三龄第1天蚕粪DNJ含量最高,然后逐渐下降,从五龄第2天至五龄第7天趋于平缓,其中五龄第4天含量最低。发酵后蚕粪DNJ含量平均提高20%,最高为五龄第4天,提高40.8%。关于家蚕对DNJ的吸收和排泄机制有待于进一步深入研究。
1-Deoxynorijimycin (DNJ) as a kind of polyhydroxy piperidines was also called iminosugar for its configuration similar with sugar. DNJ appeared to be useful in food and medicine for its potential biological activities, such as inhibition of abnormal elevation of plasma glucose, anti-virus and anti-tumor. Therefore, DNJ had long been of interest for its suppressing the plasma glucose content with general consents. Mulberry resource enriched in DNJ, which can prohibit the bioactivities of intestinal alpha-glucosidase in vivo, and whose content in sericulture biomass was considered as one of significant indexes for effect on inhibition of postprandial glycemia. From the perspectives of extraction of DNJ from the silkworm with proficiency and elevation of DNJ content in sericulture resource by fermentation, this study focused on diluted acid extraction of DNJ from silkworm with surface response methodology (RSM), investigated a advantageous strain with fermentation conditions optimized by PB design and RSM, which could enhanced the DNJ content to a large extent from mulberry leaves, and groped for a prospect for production of DNJ from other sericulture resource fermented by the specific microorganism. Based on the results of this study, it is foreseen that production of DNJ and sericulture development of deep level would have the performance improved. Main results are as the following:
The formula of diluted acid extraction of DNJ from silkworm with RSM could expressed as Y= 0.47+ 0.054X_1 - 0.03X_2- 0.00925X_3+ 0.03X_1X_2- 0.07X_1X_3- 0.059X_2X_3- 0.013X_1~2 - 0.027X_2~2 + 0.024X_3~2 , Which was significant and could elucidate impact of extraction factors on DNJ content from silkworm. The optimal extraction conditions were defined as: 72.9℃, 3 hours for 18 minutes and 1:282 of solid to liquid. The DNJ extracted after optimization was 0.493%, while predicted value was 0.487%, reflecting the both was consent with each other. There were obvious mutual interactions among the extraction time, temperature and the ratio of material to liquid throughout Contour line plot and response surface graph of DNJ yield.
In compare with eight strains as starter cultures, Ganoderma lucidum was defined as the candidate for the fermentation by conversion of mulberry leaves into DNJ. And then analyzing eight factors effects on yield of DNJ fermented by Ganoderma lucidum by Plackett-Burman design, the range of pH, content of potassium nitrate and inoculum size was utilized for the following study, that is to say, for the single factor assay. The regression model for the optimizing the fermentation conditions was expressed as Y=0.054-9.37×10-4X1+1.25×10-5X2+5×10-5X3- 9.75×10-4X1X2+ 1.5×10-4X1X3+6.5×10-4X2X3-7.32×10-3X 12 -9.27×10-3X 22 -7.25×10-3 X 32 , Which was significantly appropriate and could elucidate impact of fermentation factors on DNJ content from mulberry. The highest amount of DNJ yield (0.548%) from the incubation broth by Ganoderma lucidum, in which fermentation broth showed better performance than origin before fermentation, would be calculated by first order local deviation with equivalence to zero, when X1, X2 and X3 received 6.97, 0.81% and 2.00 ml, respectively. There were obvious mutual interactions among the ph range, content of potassium nitrate and the inoculum size throughout Contour line plot and response surface graph of DNJ yield, suggesting the model was reliable and feasible.
The distribution of DNJ in mulberry was shown that most important independent parts were upper leaves, roots, middle leaves (equaled to cortex), bottom leaves in order by content, suggesting DNJ mostly was produced by the young leaves. In compare with three methods of drying silkworm powders, indicating that lyophilization was the best approach to deal with it, suggesting its structure would be greatly maintained by lyophilization and DNJ molecule would be degraded or denatured under hot-air involved circumstance the elevation of DNJ content fermented by microorganism from mulberry was more than from silkworm. In compare with the unfermented, the DNJ contents increased by 20.8% in mulberry and 6.9% in silkworm powder, respectively. The content of DNJ in feces before or after fermentation decreased swiftly during the 6 days, followed mildly for the rest of days till mounting, appearing to be lowest in feces on 4th day of fifth-instar larvae. And the DNJ yield in feces fermented by given microorganism was higher than one in feces primitive, 20 percent promotion in average. However, DNJ content in feces on 4th day of fifth-instar larvae advanced most, up to 40.8%. The circulation and excretion mechanism of DNJ accumulated by the larvae of Bombyx mori will be investigated for the further study.
引文
[1]谭仁祥.植物成分分析[M].北京:科学出版社. 2002. 365-385.
[2] A. L.Shelton. Variable chemical defenses in plants and their effect on herbivore behavior[J]. Ecology Research. 2000, 2:231-249.
[3]王峰鹏.生物碱化学[M].北京:化学工业出版社. 2008. 71-90.
[4] M. Yagi, T. Kouno, Y. Aoyagi, et al. The structure of Moranoline, a piperidine alkaloid from Morus species[J]. Nippon Nougei Kagaku Kaishi. 1976, 50(11):571-572.
[5] M. S. Butt, A. Nazir, M. T. Sultan, et al. Morus alba L. nature’s functional tonic[J]. Food Sciene &Technology. 2008, 19:505-512.
[6] Y. Ezure, S. Maruo, K. Miyazaki, et al. Moranoline (1-deoxynojirimycin) fermentation and its improvement[J]. Agric. Bio. Chem. 1985, 49(4):1119-1125.
[7]盛龙生,苏焕华,郭丹滨等.色谱质谱联用技术[M].北京:化学工业出版社. 2006. 236.
[8] B. Boris, M. G. Harry, D. B. Terry, et al. Crystal structures of complexes of N-butyl-and N-Nonyl-Deoxynojirimycin bound to acidβ-glucosidase[J]. Biological Chemistry. 2007, 282(39):29052-29058.
[9] M. Shibano, Y. Fujimoto, K. Kushino, et al. Biosynthesis of 1-deoxynojirimycin in Commelina communis: a difference between the microorganisms and plants[J]. Phytochemistry. 2004, 65:2661-2665.
[10] N. Asano, N. Makoto, M. Miwa, et al. Polyhydroxylated pyrrolidine and piperidine alkaloids from adenophora triphyua var. Japonica(campanulaceae)[J]. Phytochemistry. 2000, 53(2):379-382.
[11]殷浩.桑树和家蚕对DNJ的富集规律及桑籽降啦糖作用研究[D].山东:山东农业大学林学院.2009. 21-27.
[12] N. Asano, K. Atusushi, M. Miwa, et al. Nitrogen-containing furanose and pyranose analogues from Hyacinthus orientalis[J]. Nat. Prod. 1998, 61(5):625-628.
[13]陈松,刘宏程,储一宁等. 12个桑树品种桑叶中的1-脱氧野尻霉素含量测定与分析[J].蚕业科学. 2007, 33(4):637-641.
[14]张作法,金洁,时连根.反相高效液相色谱法测定桑枝中1-脱氧野尻霉素的含量[J].中国药学杂志. 2007, 42(7):535-538.
[15]刘卫旗,朱祥瑞.桑树不同部位DNJ的含量分析[J].蚕桑通报. 2006, 37(4):31-34.
[16]周炎,刘朝良,王莹.桑不同部位水提物中DNJ的含量分析.第六届中国国际丝绸会议论文. 2007. 25-28.
[17]鲁战会,吴文生,唐健等.桑叶功效成分含量与产地关联性研究[J].食品科技. 2007, 1:75-79.
[18]邢辉,李勇,张金芳等.桑树组织培养物种1-脱氧野尻霉素的产生规律初探[J].蚕业科学. 2008, 34(2):322-326.
[19]沈以红,朱见,代方银等.野桑蚕和不同蚕品系幼虫体内1-脱氧野尻霉素含量测定[J].蚕业科学. 2007, 33(4):674-677.
[20] Y. P. Zhu; K Yamaki.; T. Yoshihashi, et al. Purification and identification of 1-deoxynojimycin (DNJ) in okara fermented by Bacillus Subtilis B2 from Chinese tradition food[J]. Agricultural and Food Chemistry. 2010, 58: 4097-4103.
[21] D.J.Hardick; D.W.Hutchinson; S.J.Trew, et al. Glucose is a precursor of 1-deoxynojirimycin and 1-deoxymannonojirimycin in Streptomyces subrutilus[J]. Tetrahedron, 1992, 48(30):6285-6296.
[22] Yatsunami K, Ichida M, Onodera S. The relationship between 1-deoxynojirimycin content andα-glucosidase inhibitory activity in leaves of 276 mulberry cultivars(Morus spp.)in Kyoto, Japan. Nat. Med. 2008, 62:63-66.
[23]欧阳臻,陈钧.不同季节桑叶中1-脱氧野尻霉素含量的测定[J].分析检验. 2004, 25(10):211-214.
[24] N. Asano, T. Yamashita, K. Yasuda, et al. Polyhydroxylated Alkaloids Isolated from Mulberry Tree(Morus alba L.)and silkworms(Bombyx mori L.)[J]. 2001, 49:4208-4213.
[25] B. D. Farrel, D. E. Dussourd, C. Mitter. Escalation of plant defense: do latex and resin canals spur plant diversification[J]. Am. Nat. 1991, 138:881-900.
[26] C. Hirayama, K. Konno, N. Wasano, et al. Differential effects of sugar-mimic alkaloids in mulberry latex on sugar metabolism and disaccharidases of Eri and domesticated silkworms: Enzymatic adaptation of Bombyx mori to mulberry defense[J]. Insect Biology and Molecular Biology. 2007, 37:1348-1358.
[27]吉卯祉,彭松.有机化学[M].北京:科学出版社. 2002. 464-473.
[28]李立坤,夏建军,施荣富等.天然植物中生物碱的提取及树脂法在其纯化中的应用[J].离子交换与吸附. 2007, 23(5):475-480.
[29] N. Asano, K. Oseki, E. Tomioka, H. Kizu, et al. N-containing sugars from Morus alba and their glycosidase inhibitory activities.[J].Carbohydr.Res.1994, 259:243-255.
[30]韩伟力,刘利,张晓琦等.鲁桑叶化学成分研究[J].中国中药. 2007, 32(8):695-697.
[31] C. R. Keiner, B. Drager. Calystegine distribution in potato (Solanum tuberosum) tubers and plants[J]. Plant Sci. 2000, 150:171-179.
[32]杨文宇,万德光.桑树总生物碱分析方法与提取方法的探讨[J].时珍国医国药. 2008, 19(5):1043-1045.
[33]张庆和.高效液相色谱实用手册[M].北京:化学工业出版社. 2008. 144.
[34]陈智毅,肖更生,陈卫东等.黄血蚕中1-脱氧野尻霉素的离子色谱法测定[J].食品科学. 2004, 25(5):150-151.
[35]施新琴,崔为正,裘立群等.用反相高效液相色谱-紫外测定法测定1-脱氧野尻霉素的含量[J].蚕业科学. 2006, 32(1):146-149.
[36]罗存敏,施新琴,徐升胜等.桑叶提取物对小鼠血糖的影响及有效成分测定[J].蚕业科学. 2005, 31(4):418-421.
[37]关丽萍,郑光浩,金晴昊等. RP-HPLC测定不同地区、不同采集期桑叶中1-脱氧野尻霉素[J].中草药. 2005, 36(12):1881-1882.
[38]杨梅,刘玉明,高瑞昶.高效液相色谱法测定桑叶中1-脱氧野尻霉素的含量[J].武警医学. 2007, 18(2):121-124.
[39] T. Kimura, K. Nakagawa, Y. Saito, et al. Simple and rapid determination of 1-deoxynojirimycin in mulberry leaves[J]. 2004, 22:341-345.
[40]耿鹏,朱元元,杨洋等.桑树资源中1-脱氧野尻霉素的测定及其生物活性分析[J].中草药. 2005, 36(8):1151-1153.
[41]欧阳臻,李永辉,徐卫东等.高效液相色谱-荧光检测法测定桑叶中1-脱氧野尻霉(DNJ)含量[J].中国中药. 2005,30(9):682-685.
[42] H. R. Mellor, A. Adam, F. M. Platt, et al. High-Performance Cation-Exchange Chromatography and Plused Amperometric Detection for the Separation, Detection, and Quantitation of N-Alkylated sugars in Biological Samples.[J]. Analytical Biochemistry, 2000, 284:136.
[43]李宏,钱永华,王建芳等.桑叶中1-脱氧野尻霉素(DNJ)的气相测定[J].北方蚕业. 2006, 27(110):31-32.
[44]梁建宁,陈正收,吴璐等.高效液相色谱-蒸发光散射检测法测定桑白皮中1-脱氧野尻霉素的含量[J].药物分析. 2006, 26(7):905-907.
[45]李凡,裘雅渔,钱文春等.桑叶总生物碱和1-脱氧野尻霉素的含量考察[J].中国药学. 2008, 43(3):176-179.
[46]欧阳臻,陈钧,李永辉.柱前衍生化高效液相色谱荧光检测法测定桑叶中的1-脱氧野尻霉素[J].分析化学. 2005, 33(6):817-820.
[47]谢慧明,吴芳睿,杨毅等.柱前衍生化高效液相色谱-荧光检测法测定桑叶中的1-脱氧野尻霉素[J].色谱. 2008, 26(5):634-636.
[48]高小平,张蔚瑜,邹文俊等.中药提取物中α-葡萄糖苷酶抑制剂的筛选[J].天然产物研究与开发. 2003, 115:536.
[49] C. S. Rye, S. G. Withers. Glycosidase mechanisms[J]. Current opinion in Chemical Biology, 2000, 4(5):573-580
[50] M. Yoshimizu, Y. Tajima, F. Matsuzawa, et al. Binding parameters and thermodynamics of the interaction of imino sugars with a recombinant human acidα-glucosidase(alglucosidase alpha): Insight into the complex formation mechanism[J]. Clinica Chimica Acta. 2008, 391:68-73.
[51] A. Sasaki, Y. Seino, C. Ito, et al. Report of the Committee on the classification and diagnostic criteria of diabetes mellitus[J]. Diabetes Research and Clinical Practice. 2002, 55(1):65-85.
[52] Y. Yoshikuni, Y. Ezure, Y. Aoyagi, et al. Inhibition of intestinalα-glucosidase activity and postprandial hyperglycemia by moranoline and its N-alkyl derivatives[J]. Agric. Biol. Chem. 1998, 52(1):121-128.
[53] K. Nakagawa, H. Kubota, T. Kimura, et al. Occurrence of orally Administered Mulberry 1-deoxynojirimycin in Rat Plasma[J]. Agricultural Food Chemistry. 2007, 55:8928-8933.
[54]杨海霞,朱祥瑞. 1-脱氧野尻霉素(DNJ)的研究进展[J].蚕桑通报. 2003, 34(1):6-10.
[55]吴酬飞,许杨,李燕萍.α-葡萄糖苷酶抑制剂筛选模型的研究进展[J].国际药学研究. 2008, 35(1):9-12.
[56]胡竟一,雷玲,刘亚欧等.桑叶的α-葡萄糖苷酶抑制作用的研究[J].中药药理与临床. 2006, 22(6):44-45.
[57] A. N. Singab, H. A. El-Beshbishy, M. Yonekawa, et al. Hypoglycemic effect of Egyptian Morus alba root bark extract: effect on diabetes and lipid peroxidation of streptozotocin-induced diabetic rats[J]. Ethnopharmacology. 2005, 100:333-338.
[58]桂仲争,陈杰,陈伟华等.全蚕粉(SP)降血糖的作用效果及其机理的研究[J].蚕业科学. 2001, 27(2):114-118.
[59] K. S. Ryu, H. S. Lee, S. H. Chung, et al. An activity of lowering Blood-glucose levels according to preparative condition of silkworm powder[J]. Korean J Seric Sci. 1999, 41(1):9-13.
[60]李宏,黄金山,胡浩等. QHL3对α-葡萄糖苷酶活力影响及降糖机理研究[J].西北农业学报. 2003, 12(1):103-106.
[61]肖辉,施新琴,崔为正等.全蚕粉复合物降血糖及降血脂效果的比较[J].蚕业科学. 2005, 31(2):171-174.
[62] T. Kimura, K. Nakagawa, H. Kubota, et al. Food-Grade Mulberry Powder Enriched with 1-Deoxynojirimycin Suppresses the Elevation of Postprandial Blood Glucose in Humans[J]. Agricultural and Food Chemistry. 2007, 55:5869-5874.
[63]郭玉娜,王仲孚,黄琳娟.植物来源的糖类似物-多羟基生物碱的研究紧张[J].有机化学, 2007, 27(11):1337-1344.
[64]王镜岩,柱圣庚,徐长法等.生物化学(上)[M].第三版.北京:高等教育出版社. 2003, 56-75.
[65]吴敏毓,刘恭值.医学免疫学[M].合肥:中国科学技术出版社. 2002, 77-101.
[66] F. Eummanuel, J. P. Marie, M. J. Ian, et al. Recombinant HIV envelope expressed in anα-glucosidase 1-deficient CHO cell line and its parental cell line in the presence of 1-deoxynojirimycin is functional[J]. Virology. 1997, 231(1):89-95.
[67] P. S. Sunkara, T. L. Bowlin, P. S. Liu, et al. Antiretroviral activity of castanospermine and deoxynojirimycin, specific inhibitors of glycoprotein processing[J]. Biochemical and Biophysical Research Communications. 1987, 148(1):206-210.
[68] G. B. Karlsson, T. D. Butters, R. A. Dwek, et al. Effects of imino sugar N-Butyldeoxynojirimycin on the N-glycosylation of recombinant gp120[J]. Biol. Chem. 1993, 268(1):570-576.
[69] P. B. Fischer, M. Collin, G. B. Karlsson, et al. Theα-glucosidase inhibitor N-butyldeoxynojirimycin inhibits Human Immunodeficiency Virus entry at the level of Post-CD4 binding[J]. Virology. 1995, 69(9):5791-5797.
[70] P. B. Fischer, G. B. Karlsson, T. D. Butters, et al. N-butyldeoxynojirimycin-Mediated Inhibition of Human Immunodeficiency Virus Entry Correlates with Changes in Antibody Recognition of the V1/V2 Region of gp120[J]. Virology. 1996, 70(10):7143-7152.
[71] P. B. Fischer, G. B. Karlsson, R. A. Dwek, , et al. N-butyldeoxynojirimycin-mediated inhibition of Human Immunodeficiency Virus entry correlates with impaired gp120 shedding and gp41 exposure[J]. virology. 1996, 70(10):7153-7160.
[72]周正任.病原生物学[M].北京:科学出版社.2004,392-400.
[73] C. Lazar, D. Durantel, A. Macovei, et al. Treatment of hepatitis B virus-infected cells withα-glucosidase inhibitors results in production of virions with altered molecular composition and infectivity[J]. Antiviral Research. 2007, 76:30-37.
[74] J. R. Jacob, K. Mansfield, J. E. You, et al. Natural iminosugar derivatives of 1-deoxynojirimycin inhibit glycosylation of Hepatitis Viral envelope proteins[J]. Microbiology. 2007, 45(5):431-440.
[75]彭忠田,申璀,谭德明等.脱氧野尻霉素衍生物抗乙型肝炎病毒的体外试验研究[J].药物研究. 2007, 18(1):22-24.
[76] K. Olden, P. Breton, K. Grzegorzewski, et al. The potential importance of swainsonine in therapy for cancers and immunology[J]. Pharmacol. Ther. 1991, 50(3):285-290.
[77] G. K. Ostrander, N. K. Scribner. Inhibition of V-fms–induced tumor growth in nude mice by castamosper mine[J]. Cancer Research. 1998, 48:1091-1094.
[78] I. Tsuruoka, H. Fukuyasu, M. Ishii, et al. Inhibition of mouse tumor metastasis with Nojirimycin-related compounds[J]. Antibiotics. 1996, 49(2):155-161.
[79]原爱红,马骏,谢祥成等. 1-脱氧野尻霉素对高糖刺激大鼠系膜细胞增殖的影响[J].中华内分泌代谢. 2007, 23(6):550-552.
[80] Y. X. Zhao, Y. Zhou, K. M. O’boyle, et al. Hybrids of 1-deoxynojirimycin and aryl-1, 2, 3-triazoles and biological studies related to angiogenesis[J]. Bioorganic&Medicinal Chemistry. 2008, 16:6333-6337.
[81] C. Kuriyama, O. Kamiyama, K. Ikeda, et al. In viro inhibition of glycogen-degrading enzymes and glycosidases by six-membered sugar mimics and their evaluation in cell cultures[J]. Bioorganic&Medicinal Chemistry. 2008, 16:7330-7336.
[82]郭文璟,许关煜.具有开发价值的活性物质亚胺基糖[J].上海医药. 2006, 27(6):259-261.
[83] B. Islam, S. N. Khan, I. Haque, et al. Novel anti-adherence activity of mulberry leaves: inhibition of Streptococcus mutans biofilm by 1-deoxynojirimycin isolated from Morus alba[J]. Antimicrobial Chemotherapy. 2008, 62:751-757.
[84]王艳,张爱珍,任春生.正交试验设计与优化的理论基础与应用进展[J].分析试验室. 2008, 27:333-334
[85]彭海滨.正交试验设计与数据分析方法[J].计量与测试技术. 2009, 36(12):39-42.
[86]蒋运钢,贾俊强,桂仲争.响应面分析法优化家蚕1-脱氧野尻霉素的稀酸浸提工艺[J].基因组学与应用生物学. 2010, 29(4):703-710.
[87]刘树兴,花俊丽,陈素娟.桑叶中1-脱氧野尻霉素(DNJ)和多糖提取工艺优化[J].陕西科技大学学报. 2008, 26(5):55-58.
[88]王海宁,谢印芝,樊飞跃,刘培勋,龙伟.微波辅助提取竹叶柴胡总黄酮的正交实验筛选[J].解放军药学. 2008, 24(4):311-313.
[89] C. Vichasilp, K. Nakagawa, P. Sookwong, et al. Optimization of 1-deoxyrijimycin extraction from mulberry leaves by using response surface methodology[J]. Biosci. Biotechnol. Biochem. 2009, 73(12):2684-2689.
[90] T. Iwasa, H. Yamamoto, M. Shibata. Studies on validamycins, new antibiotic I. Streptomyces hygroscopicus var. limoneus. Validamycin producing organism. Journal of Antibiotechnology, 1970, 23:595–602.
[91] D. D. Schmidt, W. Frommer, B. Junge, et al. Alpha-glucosidase inhibitors, new complex oligosaccharides of microbial origin. Naturwissenschaften. 1977, 64:535–536.
[92] Y. Kameda, N. Asano, O. Wakae, et al. Microbial glycosidation of validamycins.ⅡThe preparationof alpha- and beta-D-glucoside analogs of validamycins[J]. Antibiotics. 1980, 33(7):764-6.
[93] D. C. Stein, L. K. Kopec, R. E. Yasbin, et al. Characterization of Bacillus subtilis DSM704 and its production of 1-deoxynojirimycin[J]. Appl. Environ. Microbiol. 1984. 280–284.
[94] M. Kojima; N. Tachikake, Y. Kyotani, et al. Effect of dissolved oxygen an pH on moranoline (1-deoxyrijimycin) fermentation by Streptomyces lavedulae[J]. Fermentation and Bioengineering. 1995, 79(4):391-394,
[95] C. Hansawasdi, J. Kawabata.α-glucosidase inhibitory effect of mulberry (Morus alba)leaves on Caco-2[J]. Fitoterapia. 2006, 77:568-573.
[96] H. B. Kim, W. Y. Choung, K. S. Ryu, et al. Sensory characteristics and blood glucose lowering effect of ice-cream containing mulberry leaf powder[J]. Korean J. Seric. Sci. 1999, 15(6):129-134.
[97]马静,刘树兴.桑枝中1-脱氧野尻霉素(DNJ)的研究进展[J].食品科技. 2006, 9:112-115.
[98]陈静,程永强,刘晓庆等.食品中α-葡萄糖苷酶抑制剂的研究进展[J].食品科学. 2007, 28(4):360-363.
[99] A. E. Stüze. Iminosugars as glycosidase inhibitors: Nojirimycin and Beyond[M]. Weinheim:Wiley-VCH. 1999.
[100] N. Asano, R. J. Nash, R. J. Molyneux, et al. Sugar-mimic glycosidase inhibitors: natural occurrence, biological activity and prospects for therapeutic application[J]. Tetrahedron: Asymmetry. 2000, 11(8):1645-1680.
[101] L. L. Tian, Z. J. Lee, H. Lee. Synthesis of Deoxynojirimyciin[J]. Appl. Chem. 2004, 21:12.
[102] X. Z. Song, R. I. Hollingsworth. Facile synthesis of 1-deoxynojirimycin(DNJ) and 1-deoxymannojirimycin(DMJ)[J]. Tetrahedron Letters. 2007, 48:3115-3118.
[103] E. Danieli, J. Lalot, P. V. Murphy. Selective protecting group manipulations on the 1-deoxynojirimycin scaffold[J]. Tetrahedron. 2007, 63:6827-6834.
[104] T. Anno, K. Tamura, H. Oono. Maltose, sucrase andα-amylase inhibitory activity of Morus leaves extract[J]. Food Preserve Science. 2004, 30:223-229.
[105] G. Leglar. Glycosidase hydrolases: mechanistic information from studies with reversible inhibitors[J]. Advance in Carbohydrate Chemical and Biochemistry. 1990,48:319-364.
[106] N. Asano, H. Kizu, K. Oseki, et al, N-alkylated nitrogen in the ring sugars: conformational basis of inhibition of glycosidases and HIV-1 replication[J]. Medical Chemistry. 1995, 38:2349-2356.
[107] A. Mehta, S. Carrouee, B. Conyers, et al. Inhibition of hepatitis B virus DNA replication by imino sugars without the inhibition of the DNA polymerase: therapeutic implications[J]. Hepatology. 2001, 33:1488-1495.
[108] T. Cox, R. Lachmann, C. Hollak, et al. Novel oral treatment of Gaucher's disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis[J]. Lancet. 2000, 355: 481-1485.
[109]娄德帅,范涛,桂仲争等.全蚕粉1-脱氧野尻霉素(DNJ)的分离及其分离物对HeLa肿瘤细胞抑制作用[J].蚕业科学. 2010, 36(1):109-114.
[110]李宇亮,李剑敏,吴雅睿. 1-脱氧野尻霉素提取分离方法研究[J].应用化工. 2006, 35(9):659-665.
[111]赵艳红,李建科.响应曲面法建立超声波辅助提取石榴皮多酚数学模型[J].农产品加工. 2009, 166:126-131.
[112] J.W. Kim, S.U. Kim, H.S. Lee, et al. Determination of 1-deoxynojirimycin in Morus alba L. leaves by derivatization with 9-fluorenylmethyl chloroformate followed by reversed-phase high-performance liquid chromatography[J]. Chromatography A. 2003, 1002:93-99.
[113]胡瑞军,车振明,徐丹等.微波辅助提取桑叶生物碱DNJ的工艺研究[J].食品科技. 2007, 8:139-141.
[114]龚盛昭,杨卓如,曾海宇.微波提取黄芪甲苷的工艺研究[J].中成药. 2005, 27(8):889
[115] K. Hummert, W. Vetter, B. Luckas. Determination of organochlorine compounds in fatty tissue of marine mammals by application of microwave extraction[J]. Chromatographia. 1996, 42:300.
[116]张丁倩,柯丽霞,赵文科等.混菌发酵油菜秆氮源对灵芝木质素酶系的影响[J].中国食用菌. 2010, 29(1):39-41.
[117]欧宏宇,贾士儒. SAS软件在微生物培养条件优化中的应用[J].天津轻工业学院学报. 2001, 36:14-15.
[118]王爱成.灵芝[M].北京:科学技术出版社. 2002, 12-163.
[119]王伟,尚德静,温磊.灵芝发酵菌丝三萜类化合物含量的测定[J].中国食用菌. 2006, 25(1):30-32.
[120]张金芳,殷浩,叶晶晶等.培养基成分对组培桑苗叶片中1-脱氧野尻霉素含量的影响[J].蚕业科学. 2008, 34(3):400-404.
[121]李雁群,张莲芬,张志斌等.苦参灵芝发酵液在2.2.15细胞中抗HBV作用[J].无锡轻工业大学学报. 2004, 23(2):98-100.
[122] J. J. Gao, A. Hirakawa, B. S. Min, et al. In vivo antitumor effects of bitter principles from the antered form of fruiting bodies of Ganoderma lucidum[J]. Nat. Med. 2006, 60:42-48.
[123] Hardick D.J.; Hutchinson D.W.; Trew S.J., et al. The biosynthesis of deoxynojirimycin and deoxymannojirimycin in Streptomyces Subrutilus. Chemistry Society, Chemistry Community. 1991, 729-730.
[124] Hardick D.J., Hutchinson D.W.. The biosynthesis of 1-deoxynojirimycin in Bacillus subtilis var niger. Tetrahedron, 1993, 49(20):6707-6716.
[125]陈志杰,顾振新,解春艳.灵芝发酵过程中营养物质及相关酶活性变化研究[J].中国酿造. 2008, 178:26-29.
[126] Y. L. Zhong, S. Morimura, K. Kida. Effect of fermentation temperature on relationship between cell viability and trehalose content of Saccharomyces cerevisiae KF-7 in repeated-batch fermentation[J]. Fermentation and Bioengineering. 1995, 80(2):204-207.
[127]李刚,李宝健.灵芝发酵培养基的研究[J].药用植物栽培. 1998, 21(8):379-381.
[128]杨玲英.桑叶茶的作用及生产加工技术[J].食品科学. 2010, 11:348-350.
[129]于翠,胡兴明,邓文等.植物根际微生物研究及其在桑树上的利用[J].蚕桑通报. 2010, 41(2):1-5.
[130]靳通收,马艳然.从蚕粪中提取果胶和叶绿素[J].日用化学工业. 1997, 5(18):54.
[131]桂仲争,庄大桓.全蚕粉及其生理功能[J].中国蚕业. 2000(2):53-54.
[132] E. D. Faber, R.Oosting, J.J. Neefjes, et al. Distribution and elimination of the glycosidases inhibitors 1-deoxynojirimycin and N-methyl-1-deoxynojirimycin in the rat in vivo[J]. Pharmaceutical Science. 1992, 9:1442-1450.
[133] C. Hirayama, K. Konno, N. Wasano, et al. Differential effects of sugar-mimic alkaloids in mulberry latex on sugar metabolism and disaccharidases of Eri and domestic silkworms: enzymatic adaption of Bombyx mori to mulberry defense[J]. Insect Biochemistry and Molecular Biology. 2007, 37:1348-1358.
[134] Y. P. Zhu, L. J. Yin, Y. Q. Cheng, et al. Effects of sources of carbon and nitrogen on production of alpha-glucosidase inhibitor by a newly isolated strain of Bacillus subtilis B2[J]. Food Chemistry. 2008, 109:737-742.
[2] A. L.Shelton. Variable chemical defenses in plants and their effect on herbivore behavior[J]. Ecology Research. 2000, 2:231-249.
[3]王峰鹏.生物碱化学[M].北京:化学工业出版社. 2008. 71-90.
[4] M. Yagi, T. Kouno, Y. Aoyagi, et al. The structure of Moranoline, a piperidine alkaloid from Morus species[J]. Nippon Nougei Kagaku Kaishi. 1976, 50(11):571-572.
[5] M. S. Butt, A. Nazir, M. T. Sultan, et al. Morus alba L. nature’s functional tonic[J]. Food Sciene &Technology. 2008, 19:505-512.
[6] Y. Ezure, S. Maruo, K. Miyazaki, et al. Moranoline (1-deoxynojirimycin) fermentation and its improvement[J]. Agric. Bio. Chem. 1985, 49(4):1119-1125.
[7]盛龙生,苏焕华,郭丹滨等.色谱质谱联用技术[M].北京:化学工业出版社. 2006. 236.
[8] B. Boris, M. G. Harry, D. B. Terry, et al. Crystal structures of complexes of N-butyl-and N-Nonyl-Deoxynojirimycin bound to acidβ-glucosidase[J]. Biological Chemistry. 2007, 282(39):29052-29058.
[9] M. Shibano, Y. Fujimoto, K. Kushino, et al. Biosynthesis of 1-deoxynojirimycin in Commelina communis: a difference between the microorganisms and plants[J]. Phytochemistry. 2004, 65:2661-2665.
[10] N. Asano, N. Makoto, M. Miwa, et al. Polyhydroxylated pyrrolidine and piperidine alkaloids from adenophora triphyua var. Japonica(campanulaceae)[J]. Phytochemistry. 2000, 53(2):379-382.
[11]殷浩.桑树和家蚕对DNJ的富集规律及桑籽降啦糖作用研究[D].山东:山东农业大学林学院.2009. 21-27.
[12] N. Asano, K. Atusushi, M. Miwa, et al. Nitrogen-containing furanose and pyranose analogues from Hyacinthus orientalis[J]. Nat. Prod. 1998, 61(5):625-628.
[13]陈松,刘宏程,储一宁等. 12个桑树品种桑叶中的1-脱氧野尻霉素含量测定与分析[J].蚕业科学. 2007, 33(4):637-641.
[14]张作法,金洁,时连根.反相高效液相色谱法测定桑枝中1-脱氧野尻霉素的含量[J].中国药学杂志. 2007, 42(7):535-538.
[15]刘卫旗,朱祥瑞.桑树不同部位DNJ的含量分析[J].蚕桑通报. 2006, 37(4):31-34.
[16]周炎,刘朝良,王莹.桑不同部位水提物中DNJ的含量分析.第六届中国国际丝绸会议论文. 2007. 25-28.
[17]鲁战会,吴文生,唐健等.桑叶功效成分含量与产地关联性研究[J].食品科技. 2007, 1:75-79.
[18]邢辉,李勇,张金芳等.桑树组织培养物种1-脱氧野尻霉素的产生规律初探[J].蚕业科学. 2008, 34(2):322-326.
[19]沈以红,朱见,代方银等.野桑蚕和不同蚕品系幼虫体内1-脱氧野尻霉素含量测定[J].蚕业科学. 2007, 33(4):674-677.
[20] Y. P. Zhu; K Yamaki.; T. Yoshihashi, et al. Purification and identification of 1-deoxynojimycin (DNJ) in okara fermented by Bacillus Subtilis B2 from Chinese tradition food[J]. Agricultural and Food Chemistry. 2010, 58: 4097-4103.
[21] D.J.Hardick; D.W.Hutchinson; S.J.Trew, et al. Glucose is a precursor of 1-deoxynojirimycin and 1-deoxymannonojirimycin in Streptomyces subrutilus[J]. Tetrahedron, 1992, 48(30):6285-6296.
[22] Yatsunami K, Ichida M, Onodera S. The relationship between 1-deoxynojirimycin content andα-glucosidase inhibitory activity in leaves of 276 mulberry cultivars(Morus spp.)in Kyoto, Japan. Nat. Med. 2008, 62:63-66.
[23]欧阳臻,陈钧.不同季节桑叶中1-脱氧野尻霉素含量的测定[J].分析检验. 2004, 25(10):211-214.
[24] N. Asano, T. Yamashita, K. Yasuda, et al. Polyhydroxylated Alkaloids Isolated from Mulberry Tree(Morus alba L.)and silkworms(Bombyx mori L.)[J]. 2001, 49:4208-4213.
[25] B. D. Farrel, D. E. Dussourd, C. Mitter. Escalation of plant defense: do latex and resin canals spur plant diversification[J]. Am. Nat. 1991, 138:881-900.
[26] C. Hirayama, K. Konno, N. Wasano, et al. Differential effects of sugar-mimic alkaloids in mulberry latex on sugar metabolism and disaccharidases of Eri and domesticated silkworms: Enzymatic adaptation of Bombyx mori to mulberry defense[J]. Insect Biology and Molecular Biology. 2007, 37:1348-1358.
[27]吉卯祉,彭松.有机化学[M].北京:科学出版社. 2002. 464-473.
[28]李立坤,夏建军,施荣富等.天然植物中生物碱的提取及树脂法在其纯化中的应用[J].离子交换与吸附. 2007, 23(5):475-480.
[29] N. Asano, K. Oseki, E. Tomioka, H. Kizu, et al. N-containing sugars from Morus alba and their glycosidase inhibitory activities.[J].Carbohydr.Res.1994, 259:243-255.
[30]韩伟力,刘利,张晓琦等.鲁桑叶化学成分研究[J].中国中药. 2007, 32(8):695-697.
[31] C. R. Keiner, B. Drager. Calystegine distribution in potato (Solanum tuberosum) tubers and plants[J]. Plant Sci. 2000, 150:171-179.
[32]杨文宇,万德光.桑树总生物碱分析方法与提取方法的探讨[J].时珍国医国药. 2008, 19(5):1043-1045.
[33]张庆和.高效液相色谱实用手册[M].北京:化学工业出版社. 2008. 144.
[34]陈智毅,肖更生,陈卫东等.黄血蚕中1-脱氧野尻霉素的离子色谱法测定[J].食品科学. 2004, 25(5):150-151.
[35]施新琴,崔为正,裘立群等.用反相高效液相色谱-紫外测定法测定1-脱氧野尻霉素的含量[J].蚕业科学. 2006, 32(1):146-149.
[36]罗存敏,施新琴,徐升胜等.桑叶提取物对小鼠血糖的影响及有效成分测定[J].蚕业科学. 2005, 31(4):418-421.
[37]关丽萍,郑光浩,金晴昊等. RP-HPLC测定不同地区、不同采集期桑叶中1-脱氧野尻霉素[J].中草药. 2005, 36(12):1881-1882.
[38]杨梅,刘玉明,高瑞昶.高效液相色谱法测定桑叶中1-脱氧野尻霉素的含量[J].武警医学. 2007, 18(2):121-124.
[39] T. Kimura, K. Nakagawa, Y. Saito, et al. Simple and rapid determination of 1-deoxynojirimycin in mulberry leaves[J]. 2004, 22:341-345.
[40]耿鹏,朱元元,杨洋等.桑树资源中1-脱氧野尻霉素的测定及其生物活性分析[J].中草药. 2005, 36(8):1151-1153.
[41]欧阳臻,李永辉,徐卫东等.高效液相色谱-荧光检测法测定桑叶中1-脱氧野尻霉(DNJ)含量[J].中国中药. 2005,30(9):682-685.
[42] H. R. Mellor, A. Adam, F. M. Platt, et al. High-Performance Cation-Exchange Chromatography and Plused Amperometric Detection for the Separation, Detection, and Quantitation of N-Alkylated sugars in Biological Samples.[J]. Analytical Biochemistry, 2000, 284:136.
[43]李宏,钱永华,王建芳等.桑叶中1-脱氧野尻霉素(DNJ)的气相测定[J].北方蚕业. 2006, 27(110):31-32.
[44]梁建宁,陈正收,吴璐等.高效液相色谱-蒸发光散射检测法测定桑白皮中1-脱氧野尻霉素的含量[J].药物分析. 2006, 26(7):905-907.
[45]李凡,裘雅渔,钱文春等.桑叶总生物碱和1-脱氧野尻霉素的含量考察[J].中国药学. 2008, 43(3):176-179.
[46]欧阳臻,陈钧,李永辉.柱前衍生化高效液相色谱荧光检测法测定桑叶中的1-脱氧野尻霉素[J].分析化学. 2005, 33(6):817-820.
[47]谢慧明,吴芳睿,杨毅等.柱前衍生化高效液相色谱-荧光检测法测定桑叶中的1-脱氧野尻霉素[J].色谱. 2008, 26(5):634-636.
[48]高小平,张蔚瑜,邹文俊等.中药提取物中α-葡萄糖苷酶抑制剂的筛选[J].天然产物研究与开发. 2003, 115:536.
[49] C. S. Rye, S. G. Withers. Glycosidase mechanisms[J]. Current opinion in Chemical Biology, 2000, 4(5):573-580
[50] M. Yoshimizu, Y. Tajima, F. Matsuzawa, et al. Binding parameters and thermodynamics of the interaction of imino sugars with a recombinant human acidα-glucosidase(alglucosidase alpha): Insight into the complex formation mechanism[J]. Clinica Chimica Acta. 2008, 391:68-73.
[51] A. Sasaki, Y. Seino, C. Ito, et al. Report of the Committee on the classification and diagnostic criteria of diabetes mellitus[J]. Diabetes Research and Clinical Practice. 2002, 55(1):65-85.
[52] Y. Yoshikuni, Y. Ezure, Y. Aoyagi, et al. Inhibition of intestinalα-glucosidase activity and postprandial hyperglycemia by moranoline and its N-alkyl derivatives[J]. Agric. Biol. Chem. 1998, 52(1):121-128.
[53] K. Nakagawa, H. Kubota, T. Kimura, et al. Occurrence of orally Administered Mulberry 1-deoxynojirimycin in Rat Plasma[J]. Agricultural Food Chemistry. 2007, 55:8928-8933.
[54]杨海霞,朱祥瑞. 1-脱氧野尻霉素(DNJ)的研究进展[J].蚕桑通报. 2003, 34(1):6-10.
[55]吴酬飞,许杨,李燕萍.α-葡萄糖苷酶抑制剂筛选模型的研究进展[J].国际药学研究. 2008, 35(1):9-12.
[56]胡竟一,雷玲,刘亚欧等.桑叶的α-葡萄糖苷酶抑制作用的研究[J].中药药理与临床. 2006, 22(6):44-45.
[57] A. N. Singab, H. A. El-Beshbishy, M. Yonekawa, et al. Hypoglycemic effect of Egyptian Morus alba root bark extract: effect on diabetes and lipid peroxidation of streptozotocin-induced diabetic rats[J]. Ethnopharmacology. 2005, 100:333-338.
[58]桂仲争,陈杰,陈伟华等.全蚕粉(SP)降血糖的作用效果及其机理的研究[J].蚕业科学. 2001, 27(2):114-118.
[59] K. S. Ryu, H. S. Lee, S. H. Chung, et al. An activity of lowering Blood-glucose levels according to preparative condition of silkworm powder[J]. Korean J Seric Sci. 1999, 41(1):9-13.
[60]李宏,黄金山,胡浩等. QHL3对α-葡萄糖苷酶活力影响及降糖机理研究[J].西北农业学报. 2003, 12(1):103-106.
[61]肖辉,施新琴,崔为正等.全蚕粉复合物降血糖及降血脂效果的比较[J].蚕业科学. 2005, 31(2):171-174.
[62] T. Kimura, K. Nakagawa, H. Kubota, et al. Food-Grade Mulberry Powder Enriched with 1-Deoxynojirimycin Suppresses the Elevation of Postprandial Blood Glucose in Humans[J]. Agricultural and Food Chemistry. 2007, 55:5869-5874.
[63]郭玉娜,王仲孚,黄琳娟.植物来源的糖类似物-多羟基生物碱的研究紧张[J].有机化学, 2007, 27(11):1337-1344.
[64]王镜岩,柱圣庚,徐长法等.生物化学(上)[M].第三版.北京:高等教育出版社. 2003, 56-75.
[65]吴敏毓,刘恭值.医学免疫学[M].合肥:中国科学技术出版社. 2002, 77-101.
[66] F. Eummanuel, J. P. Marie, M. J. Ian, et al. Recombinant HIV envelope expressed in anα-glucosidase 1-deficient CHO cell line and its parental cell line in the presence of 1-deoxynojirimycin is functional[J]. Virology. 1997, 231(1):89-95.
[67] P. S. Sunkara, T. L. Bowlin, P. S. Liu, et al. Antiretroviral activity of castanospermine and deoxynojirimycin, specific inhibitors of glycoprotein processing[J]. Biochemical and Biophysical Research Communications. 1987, 148(1):206-210.
[68] G. B. Karlsson, T. D. Butters, R. A. Dwek, et al. Effects of imino sugar N-Butyldeoxynojirimycin on the N-glycosylation of recombinant gp120[J]. Biol. Chem. 1993, 268(1):570-576.
[69] P. B. Fischer, M. Collin, G. B. Karlsson, et al. Theα-glucosidase inhibitor N-butyldeoxynojirimycin inhibits Human Immunodeficiency Virus entry at the level of Post-CD4 binding[J]. Virology. 1995, 69(9):5791-5797.
[70] P. B. Fischer, G. B. Karlsson, T. D. Butters, et al. N-butyldeoxynojirimycin-Mediated Inhibition of Human Immunodeficiency Virus Entry Correlates with Changes in Antibody Recognition of the V1/V2 Region of gp120[J]. Virology. 1996, 70(10):7143-7152.
[71] P. B. Fischer, G. B. Karlsson, R. A. Dwek, , et al. N-butyldeoxynojirimycin-mediated inhibition of Human Immunodeficiency Virus entry correlates with impaired gp120 shedding and gp41 exposure[J]. virology. 1996, 70(10):7153-7160.
[72]周正任.病原生物学[M].北京:科学出版社.2004,392-400.
[73] C. Lazar, D. Durantel, A. Macovei, et al. Treatment of hepatitis B virus-infected cells withα-glucosidase inhibitors results in production of virions with altered molecular composition and infectivity[J]. Antiviral Research. 2007, 76:30-37.
[74] J. R. Jacob, K. Mansfield, J. E. You, et al. Natural iminosugar derivatives of 1-deoxynojirimycin inhibit glycosylation of Hepatitis Viral envelope proteins[J]. Microbiology. 2007, 45(5):431-440.
[75]彭忠田,申璀,谭德明等.脱氧野尻霉素衍生物抗乙型肝炎病毒的体外试验研究[J].药物研究. 2007, 18(1):22-24.
[76] K. Olden, P. Breton, K. Grzegorzewski, et al. The potential importance of swainsonine in therapy for cancers and immunology[J]. Pharmacol. Ther. 1991, 50(3):285-290.
[77] G. K. Ostrander, N. K. Scribner. Inhibition of V-fms–induced tumor growth in nude mice by castamosper mine[J]. Cancer Research. 1998, 48:1091-1094.
[78] I. Tsuruoka, H. Fukuyasu, M. Ishii, et al. Inhibition of mouse tumor metastasis with Nojirimycin-related compounds[J]. Antibiotics. 1996, 49(2):155-161.
[79]原爱红,马骏,谢祥成等. 1-脱氧野尻霉素对高糖刺激大鼠系膜细胞增殖的影响[J].中华内分泌代谢. 2007, 23(6):550-552.
[80] Y. X. Zhao, Y. Zhou, K. M. O’boyle, et al. Hybrids of 1-deoxynojirimycin and aryl-1, 2, 3-triazoles and biological studies related to angiogenesis[J]. Bioorganic&Medicinal Chemistry. 2008, 16:6333-6337.
[81] C. Kuriyama, O. Kamiyama, K. Ikeda, et al. In viro inhibition of glycogen-degrading enzymes and glycosidases by six-membered sugar mimics and their evaluation in cell cultures[J]. Bioorganic&Medicinal Chemistry. 2008, 16:7330-7336.
[82]郭文璟,许关煜.具有开发价值的活性物质亚胺基糖[J].上海医药. 2006, 27(6):259-261.
[83] B. Islam, S. N. Khan, I. Haque, et al. Novel anti-adherence activity of mulberry leaves: inhibition of Streptococcus mutans biofilm by 1-deoxynojirimycin isolated from Morus alba[J]. Antimicrobial Chemotherapy. 2008, 62:751-757.
[84]王艳,张爱珍,任春生.正交试验设计与优化的理论基础与应用进展[J].分析试验室. 2008, 27:333-334
[85]彭海滨.正交试验设计与数据分析方法[J].计量与测试技术. 2009, 36(12):39-42.
[86]蒋运钢,贾俊强,桂仲争.响应面分析法优化家蚕1-脱氧野尻霉素的稀酸浸提工艺[J].基因组学与应用生物学. 2010, 29(4):703-710.
[87]刘树兴,花俊丽,陈素娟.桑叶中1-脱氧野尻霉素(DNJ)和多糖提取工艺优化[J].陕西科技大学学报. 2008, 26(5):55-58.
[88]王海宁,谢印芝,樊飞跃,刘培勋,龙伟.微波辅助提取竹叶柴胡总黄酮的正交实验筛选[J].解放军药学. 2008, 24(4):311-313.
[89] C. Vichasilp, K. Nakagawa, P. Sookwong, et al. Optimization of 1-deoxyrijimycin extraction from mulberry leaves by using response surface methodology[J]. Biosci. Biotechnol. Biochem. 2009, 73(12):2684-2689.
[90] T. Iwasa, H. Yamamoto, M. Shibata. Studies on validamycins, new antibiotic I. Streptomyces hygroscopicus var. limoneus. Validamycin producing organism. Journal of Antibiotechnology, 1970, 23:595–602.
[91] D. D. Schmidt, W. Frommer, B. Junge, et al. Alpha-glucosidase inhibitors, new complex oligosaccharides of microbial origin. Naturwissenschaften. 1977, 64:535–536.
[92] Y. Kameda, N. Asano, O. Wakae, et al. Microbial glycosidation of validamycins.ⅡThe preparationof alpha- and beta-D-glucoside analogs of validamycins[J]. Antibiotics. 1980, 33(7):764-6.
[93] D. C. Stein, L. K. Kopec, R. E. Yasbin, et al. Characterization of Bacillus subtilis DSM704 and its production of 1-deoxynojirimycin[J]. Appl. Environ. Microbiol. 1984. 280–284.
[94] M. Kojima; N. Tachikake, Y. Kyotani, et al. Effect of dissolved oxygen an pH on moranoline (1-deoxyrijimycin) fermentation by Streptomyces lavedulae[J]. Fermentation and Bioengineering. 1995, 79(4):391-394,
[95] C. Hansawasdi, J. Kawabata.α-glucosidase inhibitory effect of mulberry (Morus alba)leaves on Caco-2[J]. Fitoterapia. 2006, 77:568-573.
[96] H. B. Kim, W. Y. Choung, K. S. Ryu, et al. Sensory characteristics and blood glucose lowering effect of ice-cream containing mulberry leaf powder[J]. Korean J. Seric. Sci. 1999, 15(6):129-134.
[97]马静,刘树兴.桑枝中1-脱氧野尻霉素(DNJ)的研究进展[J].食品科技. 2006, 9:112-115.
[98]陈静,程永强,刘晓庆等.食品中α-葡萄糖苷酶抑制剂的研究进展[J].食品科学. 2007, 28(4):360-363.
[99] A. E. Stüze. Iminosugars as glycosidase inhibitors: Nojirimycin and Beyond[M]. Weinheim:Wiley-VCH. 1999.
[100] N. Asano, R. J. Nash, R. J. Molyneux, et al. Sugar-mimic glycosidase inhibitors: natural occurrence, biological activity and prospects for therapeutic application[J]. Tetrahedron: Asymmetry. 2000, 11(8):1645-1680.
[101] L. L. Tian, Z. J. Lee, H. Lee. Synthesis of Deoxynojirimyciin[J]. Appl. Chem. 2004, 21:12.
[102] X. Z. Song, R. I. Hollingsworth. Facile synthesis of 1-deoxynojirimycin(DNJ) and 1-deoxymannojirimycin(DMJ)[J]. Tetrahedron Letters. 2007, 48:3115-3118.
[103] E. Danieli, J. Lalot, P. V. Murphy. Selective protecting group manipulations on the 1-deoxynojirimycin scaffold[J]. Tetrahedron. 2007, 63:6827-6834.
[104] T. Anno, K. Tamura, H. Oono. Maltose, sucrase andα-amylase inhibitory activity of Morus leaves extract[J]. Food Preserve Science. 2004, 30:223-229.
[105] G. Leglar. Glycosidase hydrolases: mechanistic information from studies with reversible inhibitors[J]. Advance in Carbohydrate Chemical and Biochemistry. 1990,48:319-364.
[106] N. Asano, H. Kizu, K. Oseki, et al, N-alkylated nitrogen in the ring sugars: conformational basis of inhibition of glycosidases and HIV-1 replication[J]. Medical Chemistry. 1995, 38:2349-2356.
[107] A. Mehta, S. Carrouee, B. Conyers, et al. Inhibition of hepatitis B virus DNA replication by imino sugars without the inhibition of the DNA polymerase: therapeutic implications[J]. Hepatology. 2001, 33:1488-1495.
[108] T. Cox, R. Lachmann, C. Hollak, et al. Novel oral treatment of Gaucher's disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis[J]. Lancet. 2000, 355: 481-1485.
[109]娄德帅,范涛,桂仲争等.全蚕粉1-脱氧野尻霉素(DNJ)的分离及其分离物对HeLa肿瘤细胞抑制作用[J].蚕业科学. 2010, 36(1):109-114.
[110]李宇亮,李剑敏,吴雅睿. 1-脱氧野尻霉素提取分离方法研究[J].应用化工. 2006, 35(9):659-665.
[111]赵艳红,李建科.响应曲面法建立超声波辅助提取石榴皮多酚数学模型[J].农产品加工. 2009, 166:126-131.
[112] J.W. Kim, S.U. Kim, H.S. Lee, et al. Determination of 1-deoxynojirimycin in Morus alba L. leaves by derivatization with 9-fluorenylmethyl chloroformate followed by reversed-phase high-performance liquid chromatography[J]. Chromatography A. 2003, 1002:93-99.
[113]胡瑞军,车振明,徐丹等.微波辅助提取桑叶生物碱DNJ的工艺研究[J].食品科技. 2007, 8:139-141.
[114]龚盛昭,杨卓如,曾海宇.微波提取黄芪甲苷的工艺研究[J].中成药. 2005, 27(8):889
[115] K. Hummert, W. Vetter, B. Luckas. Determination of organochlorine compounds in fatty tissue of marine mammals by application of microwave extraction[J]. Chromatographia. 1996, 42:300.
[116]张丁倩,柯丽霞,赵文科等.混菌发酵油菜秆氮源对灵芝木质素酶系的影响[J].中国食用菌. 2010, 29(1):39-41.
[117]欧宏宇,贾士儒. SAS软件在微生物培养条件优化中的应用[J].天津轻工业学院学报. 2001, 36:14-15.
[118]王爱成.灵芝[M].北京:科学技术出版社. 2002, 12-163.
[119]王伟,尚德静,温磊.灵芝发酵菌丝三萜类化合物含量的测定[J].中国食用菌. 2006, 25(1):30-32.
[120]张金芳,殷浩,叶晶晶等.培养基成分对组培桑苗叶片中1-脱氧野尻霉素含量的影响[J].蚕业科学. 2008, 34(3):400-404.
[121]李雁群,张莲芬,张志斌等.苦参灵芝发酵液在2.2.15细胞中抗HBV作用[J].无锡轻工业大学学报. 2004, 23(2):98-100.
[122] J. J. Gao, A. Hirakawa, B. S. Min, et al. In vivo antitumor effects of bitter principles from the antered form of fruiting bodies of Ganoderma lucidum[J]. Nat. Med. 2006, 60:42-48.
[123] Hardick D.J.; Hutchinson D.W.; Trew S.J., et al. The biosynthesis of deoxynojirimycin and deoxymannojirimycin in Streptomyces Subrutilus. Chemistry Society, Chemistry Community. 1991, 729-730.
[124] Hardick D.J., Hutchinson D.W.. The biosynthesis of 1-deoxynojirimycin in Bacillus subtilis var niger. Tetrahedron, 1993, 49(20):6707-6716.
[125]陈志杰,顾振新,解春艳.灵芝发酵过程中营养物质及相关酶活性变化研究[J].中国酿造. 2008, 178:26-29.
[126] Y. L. Zhong, S. Morimura, K. Kida. Effect of fermentation temperature on relationship between cell viability and trehalose content of Saccharomyces cerevisiae KF-7 in repeated-batch fermentation[J]. Fermentation and Bioengineering. 1995, 80(2):204-207.
[127]李刚,李宝健.灵芝发酵培养基的研究[J].药用植物栽培. 1998, 21(8):379-381.
[128]杨玲英.桑叶茶的作用及生产加工技术[J].食品科学. 2010, 11:348-350.
[129]于翠,胡兴明,邓文等.植物根际微生物研究及其在桑树上的利用[J].蚕桑通报. 2010, 41(2):1-5.
[130]靳通收,马艳然.从蚕粪中提取果胶和叶绿素[J].日用化学工业. 1997, 5(18):54.
[131]桂仲争,庄大桓.全蚕粉及其生理功能[J].中国蚕业. 2000(2):53-54.
[132] E. D. Faber, R.Oosting, J.J. Neefjes, et al. Distribution and elimination of the glycosidases inhibitors 1-deoxynojirimycin and N-methyl-1-deoxynojirimycin in the rat in vivo[J]. Pharmaceutical Science. 1992, 9:1442-1450.
[133] C. Hirayama, K. Konno, N. Wasano, et al. Differential effects of sugar-mimic alkaloids in mulberry latex on sugar metabolism and disaccharidases of Eri and domestic silkworms: enzymatic adaption of Bombyx mori to mulberry defense[J]. Insect Biochemistry and Molecular Biology. 2007, 37:1348-1358.
[134] Y. P. Zhu, L. J. Yin, Y. Q. Cheng, et al. Effects of sources of carbon and nitrogen on production of alpha-glucosidase inhibitor by a newly isolated strain of Bacillus subtilis B2[J]. Food Chemistry. 2008, 109:737-742.