桑树内生菌Micrococcus luteus-Y2发酵产DNJ的研究
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摘要
1-脱氧野尻霉素(DNJ)是一种α-葡萄糖苷酶抑制剂,能有效抑制糖吸收,降低血糖值。桑根皮在中国古代就被用作治疗“消渴症”的良药。现代科学已经证明,桑树中降血糖的主要有效成分是DNJ。鉴于此,前人已经对不同桑品种、桑树不同部位、不同叶位、不同季节、不同产地、甚至多种食桑昆虫的DNJ含量进行了研究,但是桑树体内DNJ的来源尚未有明确的研究结果。
目前,从中药材中提取以及利用植物内生菌获得具有疗效的活性物质成为药物研究的重要方向。本实验室在前期试验中已经从桑树中分离到两株产DNJ的内生菌:嗜麦芽寡养假单孢杆菌(Stenotrophomonas maltophilia)Y1和藤黄微球菌(Micrococcus luteus)Y2。本文对Y2菌株的生理生化指标和生物学特性进行了测定;研究了Y2菌株产DNJ的最佳发酵条件和发酵配方,并对发酵产物进行了初步分离提纯;建立了体外α-葡萄糖苷酶抑制活性测定模型,测定了Y1和Y2发酵产物粗提物对α-葡萄糖苷酶的抑制活性。同时,为探讨桑树中的DNJ来源,本试验还测定了桑树无菌苗的DNJ含量。主要研究结果如下:
1测定了Y2菌株的生理生化指标和生物学特性,结果表明Y2与藤黄微球菌的鉴定特征相符。Y2菌株接种后36 h为对数生长期,36 h~60 h是生长稳定期,60 h后开始衰老;菌株适宜生长的温度是25℃~35℃,可耐受最低生长温度为4℃,最高为40℃,最适生长温度为30℃;该菌株较适宜的pH范围是6.5~8.0,其中最适宜的pH是7.0,适宜在中性偏碱性条件下生长,并有较强的耐盐性。
2通过摇瓶培养方法,探讨了环境条件和培养基组分对Y2菌株产DNJ的影响。利用单次单因子试验确定了摇瓶发酵的最佳条件为:接种量2%(v/v)、摇瓶装液量50 mL/250 mL、发酵温度30℃、初始pH 7.0,发酵时间30 h。
在此基础上通过单次单因子试验确定了摇瓶发酵配方的最佳碳源、氮源、无机盐组合。运用PB部分因子试验分析了培养基组分:蛋白胨、麦芽糖、MgSO4、KH2PO4、NaCl对Y2菌株产DNJ的影响。结果表明,蛋白胨对Y2菌株发酵产DNJ的影响达到极显著水平,KH2PO4对Y2菌株发酵产DNJ的影响达显著水平,而麦芽糖、MgSO4、NaCl对Y2菌株发酵产DNJ的影响不显著。通过最陡爬坡路径试验逼近最大响应区域,最后用中心组合设计和响应面分析,确定了主要影响因子的最佳浓度。
最优化培养基为:麦芽糖20.00 g、蛋白胨36.53 g、KH2PO4 2.22 g、MgSO4 0.5 g、NaCl 4 g、去离子水1000 mL。
运用最佳发酵培养基和最佳发酵条件进行摇瓶发酵,利用RP-HPLC-UV法测得发酵液中DNJ的浓度达到了213.18μg/ml,较基础培养基DNJ浓度值提高了184.63%。
3对Y2菌株产生的DNJ进行了初步分离纯化。Y2菌株发酵样品进行浓缩后,又经过乙醇沉淀、过NKA-9型大孔吸附树脂和强酸型离子交换树脂,最后的样品经过浓缩、冷冻干燥成样品。提取物衍生化后利用RP-HPLC-UV法对样品进行检测,结果显示,该纯化工艺去除了大量杂质,色谱图中的杂峰大大减少,DNJ含量达到了0.337%,较之前提高了5.3倍。
4通过体外α-葡萄糖苷酶抑制模型测定了Y1、Y2菌株发酵液提取物对α-葡萄糖苷酶的抑制活性。结果表明:两种内生菌发酵分离物都具有很强的α-葡萄糖苷酶抑制活性,且最终抑制活性均高于对照药物阿卡波糖,菌株Y2发酵液提取物的抑制中浓度为111.58 mg/L,菌株Y1发酵液提取物的抑制中浓度为2307.56 mg/L,分离物的抑制活性均与浓度呈正相关,其抑制活性具有剂量依赖性。
5检测了桑树无菌苗的DNJ含量。运用细菌培养基和真菌培养基对桑树无菌苗内的内生菌检测培养,平板中没有杂菌生长,推断桑树组培苗脱毒成功,已无内生菌在其体内共生。桑树无菌组培苗干物中DNJ含量检测结果为0.197%,与大田中的桑树DNJ含量相当,证明桑树体内的DNJ不只依赖桑树内生菌的产生,桑树本身亦可合成。
1-deoxynojirimycin(DNJ) is anα-glucosidase inhibitor and could lower blood glucose efficiently. In ancient China, the root of mulberry tree was thought to be an excellent treatment for Diabetes. The modern science now proved that DNJ is the main active constituent of the mulberry tree lowering the blood glucose. View of that, former studies has determined the DNJ concentration from these materials as follows: different mulberry varieties, different mulberry positions, different leaf positions, different seasons, different metropolis as well as insects feeding on mulberry. However, there is no conclusion of the exact origin of DNJ in mulberry.
Now it becomes an important direction of researche works that obtained to active compound was extracted frome Chinese crude drug and plant endophyte. In our former studies endophytes producing DNJ stably, Y1 Stenotrophomonas maltophilia and Y2 Micrococcus luteus, have been isolated. Further researches were as follows: the determination Physiology and biochemistry indicator and bionomics of Y2, the optimization of Y2 fermenting conditions, the initial identification and characterization of DNJ produced by the endophytes, theα-glucosidase inhibition activity of fermentation crude extract. At the same time, We determined the DNJ content of germ free mulberry. The main results are as follows:
1 The determination Physiology and biochemistry indicator and bionomics of Y2. Contrast with Micrococcus luteus, the characteristic of Y2 is similar to it. Strain Y2, inoculating it, enter logarithmic growth phase in 36 h, stationary phase is 36 h~60 h, enter senescence phase after 60 h. The suitable temperature is 25℃~35℃, and minimum 4℃. maximum 40℃. The suitable pH is 6.5~8.0, and the most suitable one is 7.0. At neutral and alkaline conditions, it could grow well, and strong salt tolerance.
2 The effects of environmental conditions and nutrition of strain Y2 producing DNJ were studied through the cultivation in shake-flask fermentation.
The optimal shaking flask fermentation conditions were confirmed by one-factor-at-a-time experiment.
The optimized fermentation conditions for DNJ production were: inoculum volume 2%(v/v), solution amount 50 mL/250 mL, fermentation temperature 30℃, initial pH 7.0, fermentation time 30 h.
Based on the results above, the effects of nutrition on production of DNJ were studied involving the optimal carbon, the optimal nitrogen, inorganic salt combination by one-factor-at-a-time experiment. In the optimization of medium, the influences of peptone, maltose, MgSO4, KH2PO4 and NaCl on DNJ production were first evaluated using Plackett Burman design. Among of the test components, the effect of peptone reach extremely significant level and the KH2PO4 shows significant effect on the DNJ production. However, maltose, MgSO4 and NaCl have no significant effects on DNJ production. The path of steepest ascent was used to approach the optimal region of the medium composition. In the last step, the optimal concentrations of test components were determined by central composite design and response surface analysis.
The components of optimum medium for production of DNJ were: maltose 20.0g/L, peptone 36.53 g/L, KH2PO4 2.22 g, MgSO4 0.5 g/L, NaCl 4 g/L, demineralized water 1000 mL.
Based on the optimal fermentation condition and medium, the DNJ concentration of fermentation broth after RP-HPLC-UV reached 213.18μg/ml, 184.63% higher than that of basal medium.
3 The initial extraction, purification of DNJ produced by strain Y2 was studied by Rep-HPLC-UV analysis. Strain Y2 fermentation broth was concentrated, precipitated by ethanol, separated by NKA-9 and duolite, concentrated again, and freezed to dehydration. Determined by RP-HPLC-UV analysis after derivatization, the DNJ concentration was up to 0.337%, enhanced by 5.3 times, the sample product was purified effective.
4 Determination of theα-glucosidase inhibition activity of fermentation crude extract byα-glucosidase inhibition model in vitro. The results are as follows: The sample products both better than acarbose have effectα-glucosidase inhibition activity. The IC50 of strain Y2 is 111.58 mg/L, and Y1 is 2307.56 mg/L. Its activity is positively relative with concentration in certain range, and exhibits dose-dependent inhibition.
5 Determination of the germ free mulberry DNJ concentration. The germ free mulberry were detected with bacteria medium and fungus medium, and were proved no parachorium endophyte. Compared with mulberry growing in field, the DNJ concentration of germ free mulberry are equivalent, 0.197%. The DNJ production depended on not only endophyte but also mulberry.
目前,从中药材中提取以及利用植物内生菌获得具有疗效的活性物质成为药物研究的重要方向。本实验室在前期试验中已经从桑树中分离到两株产DNJ的内生菌:嗜麦芽寡养假单孢杆菌(Stenotrophomonas maltophilia)Y1和藤黄微球菌(Micrococcus luteus)Y2。本文对Y2菌株的生理生化指标和生物学特性进行了测定;研究了Y2菌株产DNJ的最佳发酵条件和发酵配方,并对发酵产物进行了初步分离提纯;建立了体外α-葡萄糖苷酶抑制活性测定模型,测定了Y1和Y2发酵产物粗提物对α-葡萄糖苷酶的抑制活性。同时,为探讨桑树中的DNJ来源,本试验还测定了桑树无菌苗的DNJ含量。主要研究结果如下:
1测定了Y2菌株的生理生化指标和生物学特性,结果表明Y2与藤黄微球菌的鉴定特征相符。Y2菌株接种后36 h为对数生长期,36 h~60 h是生长稳定期,60 h后开始衰老;菌株适宜生长的温度是25℃~35℃,可耐受最低生长温度为4℃,最高为40℃,最适生长温度为30℃;该菌株较适宜的pH范围是6.5~8.0,其中最适宜的pH是7.0,适宜在中性偏碱性条件下生长,并有较强的耐盐性。
2通过摇瓶培养方法,探讨了环境条件和培养基组分对Y2菌株产DNJ的影响。利用单次单因子试验确定了摇瓶发酵的最佳条件为:接种量2%(v/v)、摇瓶装液量50 mL/250 mL、发酵温度30℃、初始pH 7.0,发酵时间30 h。
在此基础上通过单次单因子试验确定了摇瓶发酵配方的最佳碳源、氮源、无机盐组合。运用PB部分因子试验分析了培养基组分:蛋白胨、麦芽糖、MgSO4、KH2PO4、NaCl对Y2菌株产DNJ的影响。结果表明,蛋白胨对Y2菌株发酵产DNJ的影响达到极显著水平,KH2PO4对Y2菌株发酵产DNJ的影响达显著水平,而麦芽糖、MgSO4、NaCl对Y2菌株发酵产DNJ的影响不显著。通过最陡爬坡路径试验逼近最大响应区域,最后用中心组合设计和响应面分析,确定了主要影响因子的最佳浓度。
最优化培养基为:麦芽糖20.00 g、蛋白胨36.53 g、KH2PO4 2.22 g、MgSO4 0.5 g、NaCl 4 g、去离子水1000 mL。
运用最佳发酵培养基和最佳发酵条件进行摇瓶发酵,利用RP-HPLC-UV法测得发酵液中DNJ的浓度达到了213.18μg/ml,较基础培养基DNJ浓度值提高了184.63%。
3对Y2菌株产生的DNJ进行了初步分离纯化。Y2菌株发酵样品进行浓缩后,又经过乙醇沉淀、过NKA-9型大孔吸附树脂和强酸型离子交换树脂,最后的样品经过浓缩、冷冻干燥成样品。提取物衍生化后利用RP-HPLC-UV法对样品进行检测,结果显示,该纯化工艺去除了大量杂质,色谱图中的杂峰大大减少,DNJ含量达到了0.337%,较之前提高了5.3倍。
4通过体外α-葡萄糖苷酶抑制模型测定了Y1、Y2菌株发酵液提取物对α-葡萄糖苷酶的抑制活性。结果表明:两种内生菌发酵分离物都具有很强的α-葡萄糖苷酶抑制活性,且最终抑制活性均高于对照药物阿卡波糖,菌株Y2发酵液提取物的抑制中浓度为111.58 mg/L,菌株Y1发酵液提取物的抑制中浓度为2307.56 mg/L,分离物的抑制活性均与浓度呈正相关,其抑制活性具有剂量依赖性。
5检测了桑树无菌苗的DNJ含量。运用细菌培养基和真菌培养基对桑树无菌苗内的内生菌检测培养,平板中没有杂菌生长,推断桑树组培苗脱毒成功,已无内生菌在其体内共生。桑树无菌组培苗干物中DNJ含量检测结果为0.197%,与大田中的桑树DNJ含量相当,证明桑树体内的DNJ不只依赖桑树内生菌的产生,桑树本身亦可合成。
1-deoxynojirimycin(DNJ) is anα-glucosidase inhibitor and could lower blood glucose efficiently. In ancient China, the root of mulberry tree was thought to be an excellent treatment for Diabetes. The modern science now proved that DNJ is the main active constituent of the mulberry tree lowering the blood glucose. View of that, former studies has determined the DNJ concentration from these materials as follows: different mulberry varieties, different mulberry positions, different leaf positions, different seasons, different metropolis as well as insects feeding on mulberry. However, there is no conclusion of the exact origin of DNJ in mulberry.
Now it becomes an important direction of researche works that obtained to active compound was extracted frome Chinese crude drug and plant endophyte. In our former studies endophytes producing DNJ stably, Y1 Stenotrophomonas maltophilia and Y2 Micrococcus luteus, have been isolated. Further researches were as follows: the determination Physiology and biochemistry indicator and bionomics of Y2, the optimization of Y2 fermenting conditions, the initial identification and characterization of DNJ produced by the endophytes, theα-glucosidase inhibition activity of fermentation crude extract. At the same time, We determined the DNJ content of germ free mulberry. The main results are as follows:
1 The determination Physiology and biochemistry indicator and bionomics of Y2. Contrast with Micrococcus luteus, the characteristic of Y2 is similar to it. Strain Y2, inoculating it, enter logarithmic growth phase in 36 h, stationary phase is 36 h~60 h, enter senescence phase after 60 h. The suitable temperature is 25℃~35℃, and minimum 4℃. maximum 40℃. The suitable pH is 6.5~8.0, and the most suitable one is 7.0. At neutral and alkaline conditions, it could grow well, and strong salt tolerance.
2 The effects of environmental conditions and nutrition of strain Y2 producing DNJ were studied through the cultivation in shake-flask fermentation.
The optimal shaking flask fermentation conditions were confirmed by one-factor-at-a-time experiment.
The optimized fermentation conditions for DNJ production were: inoculum volume 2%(v/v), solution amount 50 mL/250 mL, fermentation temperature 30℃, initial pH 7.0, fermentation time 30 h.
Based on the results above, the effects of nutrition on production of DNJ were studied involving the optimal carbon, the optimal nitrogen, inorganic salt combination by one-factor-at-a-time experiment. In the optimization of medium, the influences of peptone, maltose, MgSO4, KH2PO4 and NaCl on DNJ production were first evaluated using Plackett Burman design. Among of the test components, the effect of peptone reach extremely significant level and the KH2PO4 shows significant effect on the DNJ production. However, maltose, MgSO4 and NaCl have no significant effects on DNJ production. The path of steepest ascent was used to approach the optimal region of the medium composition. In the last step, the optimal concentrations of test components were determined by central composite design and response surface analysis.
The components of optimum medium for production of DNJ were: maltose 20.0g/L, peptone 36.53 g/L, KH2PO4 2.22 g, MgSO4 0.5 g/L, NaCl 4 g/L, demineralized water 1000 mL.
Based on the optimal fermentation condition and medium, the DNJ concentration of fermentation broth after RP-HPLC-UV reached 213.18μg/ml, 184.63% higher than that of basal medium.
3 The initial extraction, purification of DNJ produced by strain Y2 was studied by Rep-HPLC-UV analysis. Strain Y2 fermentation broth was concentrated, precipitated by ethanol, separated by NKA-9 and duolite, concentrated again, and freezed to dehydration. Determined by RP-HPLC-UV analysis after derivatization, the DNJ concentration was up to 0.337%, enhanced by 5.3 times, the sample product was purified effective.
4 Determination of theα-glucosidase inhibition activity of fermentation crude extract byα-glucosidase inhibition model in vitro. The results are as follows: The sample products both better than acarbose have effectα-glucosidase inhibition activity. The IC50 of strain Y2 is 111.58 mg/L, and Y1 is 2307.56 mg/L. Its activity is positively relative with concentration in certain range, and exhibits dose-dependent inhibition.
5 Determination of the germ free mulberry DNJ concentration. The germ free mulberry were detected with bacteria medium and fungus medium, and were proved no parachorium endophyte. Compared with mulberry growing in field, the DNJ concentration of germ free mulberry are equivalent, 0.197%. The DNJ production depended on not only endophyte but also mulberry.
引文
陈敏,王静馨.模糊正交法用于锌酵母发酵培养基条件优化的研究[J].食品与发酵工业,1994,(5):24-28.
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
陈正收,徐瑾,周应军,等.桑白皮药材中1-脱氧野尻霉素的两种含量测定方法的比较[J].中成药,2007,29(11):1654-1657
陈智毅,吴娱明,陈列辉,等.家蚕对糖尿病小鼠治疗作用的研究[J].广东蚕业,2002,36(2):35-38
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.
褚以文.微生物培养基优化方法及其OPTI优化软件[J].国外医药抗生素分册,1999,20(2):58-60.
戴开金,侯连兵,罗奇志.高效液相色谱-串联四极杆质谱法测定桑叶中1-脱氧野尻霉素[J].中药材,2009, 32(3):375-377
东秀珠,蔡妙英.常见细菌系统鉴定手册[M].科学出版社,2001
樊竹青.α-葡萄糖苷酶抑制剂治疗糖尿病的研究进展综述[J].思茅师范高等专科学校学报, 2005,21(3):3-5
方开泰.均匀试验设计的理论、方法和应用[J].数理统计与管理,2004,3(3):69-88
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,2003,15(6):536.
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):1151-1154
龚波林,耿信笃.单分散交联聚甲基丙烯酸环氧丙酷树脂的制备及亲和纯化伴刀豆球蛋白-A[J].分析化学研究报告,2003,31(8):923-927
顾江萍,梁鑫森.中药对α-葡萄糖苷酶抑制作用的研究[J].中华现代中医学杂志.2005,l(2):45-46
关丽萍,郑光浩,金晴吴,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
桂仲争,戴建一,陈军建,等.全蚕粉的食用价值及其降血糖的临床试验效果[J].蚕业科学,2004,30(1):107-110
胡竟一,雷玲,刘亚欧,等.桑叶的α-葡萄糖苷酶抑制作用研究[J].中药药理与临床, 2006,22(6):44-45
胡瑞君.川麦冬-桑叶降血糖功能性成分提取工艺的研究[D].四川成都:西华大学,硕士毕业论文, 2009
姜永涛,陈继永,刘珂.HPLC-ELSD测定桑叶中1-脱氧野尻霉素的含量[J].药物分析杂志, 2005,25(1):27-29
蒋运刚,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
李凡,裘雅渔,钱文春,等.桑叶中总生物碱和1-脱氧野尻霉素的含量考察[J].中国药学杂志,2008, 43(3):176-179
李英,张兰,杨万山,等.α-葡萄糖苷酶抑制剂的筛选和初步研究[J].上海大学学报(自然科学版),2000,6(2): 129-132
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): 659-661
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
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): 31-33
娄德帅. 1-脱氧野尻霉素(DNJ)生物合成影响因素和富含DNJ分离物对HeLa肿瘤细胞抑制作用的研究[D].江苏镇江:江苏科技大学,硕士学位论文, 2010
卢大胜,雍克岚,陈旭.广西血竭中α-葡萄糖苷酶活性抑制剂有效组分的萃取分离[J].上海大学学报(自然科学版)).2005,11(1): 71-73
陆燕,梅乐和,陆悦飞,等.响应面法优化工程菌产细胞色素P450BM23的发酵条件[J].化工学报,2006,57(5):1 187-1 192.
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
马建标,李建敏,王利民.低交换容量混胺树脂的合成及其对绞股蓝皂的吸附性能[J].高等学校化学学报,1992,13(12):1626-1629
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, 31 (9): 112-114
马庆一,陈春涛,时国庆等.天然α-葡萄糖苷酶抑制剂的研究[J].食品工业科技.2005,26(8): 51-53
孟夏,欧阳臻,常钰,等.不同产地桑叶的1-脱氧野尻霉素含量比较[J].中药材,2008,31(1):8-10
欧阳臻,陈钧.不同季节桑叶中1-脱氧野尻霉素(DNJ)含量的测定[J].食品科学,2004,25(10):211-214
欧阳臻,李永辉,徐卫东,陈钧.高效液相色谱-荧光检测法测定桑叶中1-脱氧野尻霉素(DNJ)含量[J].中国中药杂志, 2005, 30(9): 682-685
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].中国药房,2007,18(1):22-24
全吉淑,伊学哲,金明等.大豆皂苷对α-葡萄糖苷酶抑制作用的研究[J].中药材.2003,26(9): 654-656
沈佳佳,张晓军等.新型抗糖尿病药物-米格列醇的研究进展[J].海峡药学.2005,17(6):8-10
沈以红,朱见,代方银,等.野桑蚕和不同家蚕品系幼虫体内1-脱氧野尻霉素含量测定[J].蚕业科学,2007,33(4):674-677
施新琴,崔为正,裘立群,等.用反相高效液相色谱-紫外检测法测定1-脱氧野尻霉素的含量[J].蚕业科学, 2006,32(1):146-149
施新琴,肖辉,孙波,等.不同全蚕粉中的1-脱氧野尻霉素含量及其对小鼠血糖浓度的影响[J].蚕业科学, 2009,35(1):111-115
孙凌云,孙波,赵春晓,等. 26种昆虫体内的1-脱氧野尻霉素含量测定[J].蚕业科学,2010,36(3):558-563
滕利荣,孟庆繁,刘培源,等.酶法提取百合多糖及其体外氧化活性[J].吉林大学学报,2003,41(4):538-542
田丽丽,李中军,李辉. 1-脱氧氮杂-D-葡萄糖(Deoxynojirimycin, DNJ)的合成[J].应用化学, 2004,21(1): 12-15
王洪伟,崔崇士,徐雅琴.南瓜多糖复合酶法提取及纯化的研究[J].食品科学,2007,28(8):247-249
王鹏,王玉珠,沈建民.均匀设计及其在药学中的应用[J].沈阳药学院学报,1989,6(4):297-305
卫引茂,黄晓冬,陈强.连续棒状弱阳离子交换柱的合成及其对蛋白质保留行为[J].分析化学,2000,28(10):1194-1195
夏平,谢何青.复合酶法提取桑叶中多糖的工艺条件优化[J].安徽农业科学,2009,37(1):198-199
肖辉,施新琴,罗存敏,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
刑辉,李勇,张金芳,等.桑树组织培养物中1-脱氧野尻霉素的产生规律初探[J].蚕业科学.2008,34(2):322-326
许有瑞.甘草中α-葡萄糖苷酶抑制剂的筛选研究[D].甘肃兰州:兰州大学,硕士毕业论文,2006
杨海霞.桑叶中DNJ分离纯化及含量测定的研究[D].浙江杭州:浙江大学,硕士毕业论文, 2003
杨梅.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):121-123
杨雨,欧阳臻,常钰,等.桑叶不同组分降血糖作用研究[J].食品科学,2007, 28(8): 454-456
叶晶晶,殷浩,孙波,等.桑树中1-脱氧野尻霉素含量变化规律研究[J].蚕业科学, 2009,35(4):722-727
叶晶晶.桑树中产1-脱氧野尻霉素微生物的研究[D].山东泰安:山东农业大学,硕士毕业论文,2010
殷浩.桑树和家蚕对DNJ的富集规律及桑籽降血糖作用研究[D].山东泰安:山东农业大学,硕士毕业论文,2009
原爱红,马骏,蒋晓峰,等.桑叶中糖苷酶抑制活性组分的筛选及体外活性研究[J].同济大学学报, 2005,26(4):8-11
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].中华内分泌代谢杂志,2007,23(6):550-552
袁志发,周静芋.试验设计与分析(第二版)[M].高等教育出版社. 2000 张海容,韩伟珍.微波法与传统热水法浸提香菇多糖的比较研究[J].食品研究与开发,2005,26(5):68-71
张金芳.组培桑苗中1-脱氧野尻霉素含量影响因子的研究[D].山东泰安:山东农业大学,硕士毕业论文,2007
张晓臣.气相色谱法测定桑叶中1-脱氧野尻霉素含量的研究[D],陕西杨凌:西北农林科技大学,硕士毕业论文,2007
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
赵前程,滕钊,汪秋宽,刘俊荣,金桥,王翀,白鹤.复合酶法提取海带多糖的研究[J].沈阳农业大学学报,2007,38(2):220-223
周光雄,阮杰武,黄美燕,叶文才,何业伟.蚕沙中生物碱成分研究[J].中药材,2007,30(11):1384-1385
周乐春,魏兆军,张海祥,等.产1-脱氧野尻霉素微生物菌株的筛选与鉴定[J].食品科学, 2009, 30(23): 361-364
朱见.桑叶、蚕体中1-脱氧野尻霉素的含量测定与分析[D].重庆:西南大学,2008
朱建星,魏荣卿,刘晓宁.一种新型胺基树脂的制备[J].过程工程学报,2005,5(1):44-48
Asano N, Kato A, Miyauchi M, et al. Nitrogen-containing furanose and pyranose analogues from Hyacinthus orientalis [J]. Nat Prod, 1998, 61(5):625-628
Asano N, Nishida M, Miyauchi M, et al. Polyhydroxylated pyrrolidine and piperidine alkaloids from Adenophora triphylla var. japonica (Campanulaceae) [J]. Phytochemistry, 2000,53(3):379-387
Asano N, Oseki K, Kaneko E, et al. Enzymic synthesis ofα- andβ-D-glucosides of 1-deoxynojirimycin and their glycosidase inhibitory activities[J]. Carbohydr Res, 1994,258(20):255-266
Asano N, Yamashita T, Yasuda K, et al. Polyhydroxylated alkaloids isolated from mulberry trees (Morus alba L.) and silkworms (Bombyx mori L.) [J]. Food Chem, 2001,49(9):42082-42131
B. Lembcke, U.R. F?lsch, W. Creutzfeldt. Effect of 1-desoxynojirimycin derivatives on small intestinal disaccharidase activities and on active transport in vitro Digestion [J]. Digestion, 1985, 31(2-3):120-127
Barira I,Shahper NK, Irfanul H, et al. Novel anti-adherence activity of mulberry leaves: inhibition of Streptococcus mutans biofilm by 1-deoxynojirimycin isolated from Morus Alba[J].Journal of Antimicrobial Chemotherapy.2008,62(4):751-757
Beaupere D, Stasik B, Vzanet R, et al. Azidation selective du L-sorbose. Application a la synthese rapide de la 1-deoxynojirimycin[J]. Carbohydr Res,1989,191(1):163-166
Beractes R C, Ganem B. Total synthese (+)-castanospermine and (+)-deoxynojirimycin [J]. Tetrahedron,1984,25(2):165-168
Bischoff J, Kornfeld R. The effect of 1-deoxymannojirimycin on rat liver alpha-mannosidases [J]. Biochem Biophys Res Commun, 1984, 125(1):324-331
Chida N, Furuno Y, Ikemoto. et al. Synthesis of (+)- and (-)-nojirimycin and their 1-deoxyderivatives from myoinositol [J]. Carbohydr Res,1992,237(31):185-194
Daniel C, Stein T, Leslie K, et al. Characterization of Bacillus subtilis DSM704 and its production of 1-deoxynojirimycin [J]. Appl Environ Microbiol, 1984,48(2):280-284
Dennis K J, Norman R D. Projection Properties of Placket and Burman design [J]. Technometrics , 1992 , 34(4): 423-425.
Ertola R J, Giulietti A M, Castillo F J. Design, Formulation and Optimization of Media [J]. Bioprocess Technol,1995,21:89-137.
Ezure Y, Maruo S, Myazaki K, et al. Moranoline(1-deoxynojirimycin) fermentation and its improvement [J]. Agric Biol Chem, 1985,49(4):1119-1125
Frommer W, Muller L, Schmidt D D, et al. Inhibitors for glycoside hydrolases from bacilli:German,2658563[P]. 1976-12-23
Gross V, Andus T, Tran-Thi TA, et al. 1-deoxynojirimycin impairs oligosaccharide processing of alpha 1-proteinase inhibitor and inhibits its secretion in primary cultures of rat hepatocytes [J]. Biological Chemistry, 1983,258(20):12203-12209
Han J, Inoue S, Isoda H, et al. Effects of silkworm powder on glucose absorption by human intestinal epithelial cell line Caco-2[J]. Nat Med, 2007,61(4):387-390
Hardick D J, Hutchinson D W, Trew S J, et al. The biosynthesis of deoxynojirimycin and deoxymannojirimycin in Streptomyces subrutilus[J]. Chem Commun, 1991, 729-730
Hardick D J, Hutchinson D W, Trew S J, et al. Glucose is a precursor of 1-deoxynojirimycin and 1-deoxymannonojirimycin in Streptomyces subrutilus[J]. Tetrahedron, 1992,48(30):6285-6296
Hardick D J, Hutchinson D W. The biosynthesis of 1-deoxynojirimycin in Bacillus subtilis var. niger [J]. Tetrahedron, 1993,49(30):6707-6716
Inouye S, Tsuruoka T, Ito T, et al. Structure and synthesis of nojirimycin [J]. Tetrahedron,1967, 24(5):2125-2144
Jon L, Anita T, Linda J, et al. Isolation and characterization of galactoglu comannan from spruce[J]. Carbohyd Polym,2002,48(11):29-39
Jong-Anurakkun N, Bhandari M R, Hong G, et al.α-Glucosidase inhibitor from Chinese aloes[J].Fitoterapia,2008,79(6):456-457.
Kim HS, Kim YH, Hong YS. et al.α-Glucosidase inhibitors from Commelina communis [J]. Planta Med, 1999, 65(5):437-439
Kim J W, Kim S U, Lee H S, 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
Kimura T, Nakagawa K, Kubota H, et al. Food-grade mulberry powder enriched with 1-deoxynojirimycin suppresses the elevation of postprandial blood glucose in humans [J]. J Agric Food Chem, 2007, 55:5869-5874.
Kinast G, Schedel M. Production of N-substituted derivatives of 1-deoxy-nojirimycin: United States,4266025[P]. 1981-05-05
Koji D, Yoshihiko I, Tsunematsu T. Studies on the constituents of the water extract of the root of mulberry tree (Morus bombycis Koidz) [J]. Chem Pharm Bull,1986,34(5):2243-2246
Lee SS, Lin HC, Chen CK. Acylated flavonol monorhamnosides,α-glucosidase inhibitors, from Machilus philippinensis [J].Phytochemistry,2008,69(12):2347-2353.
Lembcke B, F?lsch U R, Creutzfeldt W. Effect of 1-desoxynojirimycin derivatives on small intestinal disaccharidase activities and on active transport in vitro digestion [J]. Digestion, 1985, 31(2/3):120-127
Li C, Bai JH, Cai ZL, et al. Culture medium optimization and primary kinetics analysis for nisin production[J]. Chinese Journal of Biotechnology,2001,17(2):187-192
Makio S, Koji K, Masahiko T, et al. Antioxidant constituents in the dayflower (Commelina communis L.) and theirα-glucosidase-inhibitory activity [J]. Nat Med, 2008,62(3):349-353
Maruo S, Yamashita H, Miyazaki K, et al. A novel and efficient method for enzymatic synthesis of high purity maltose using moranoline (1-deoxynojirimyein) [J]. BiosBiotechnol Biochem, 1992,56(9):1406-1409
Matsumura S, Enomoto H, Aoyagi Y, et al. Moranoline derivatives and process for preparation thereof:United States,4338433[P]. 1982-07-06
Murao S, Miyata S. Isolation and characterization of a new trehalase inhibitor S-GI [J]. Agric Biol Chem, 1980, 44(1):219-221
Nitra N, Kornkanok I, Wiroje K, et al. Quantitative determination of 1-deoxynojirimycin in mulberry leaves using liquid chromatography-tandem mass spectrometry [J]. J Pharm Biomed Anal, 2007, 44:853-858
Oku T, Yamada M, Nakamura M, et al. Inhibitory effects of extractives from leaves of Morus alba on human and rat small intestinal disaccharidase activity[J]. Nutrition, 2006, 95(5):933-938.
Paulsen H, Sangster I, Heyns K. Syntheses and reaktionen von keto-piperdinosen[J]. Chem Ber, 1969, 100:802-1001
Phuwapraisirisan P, Puksasook T, Jong-aramruang J, et al. Phenylethyl cinnamides: A new series ofα-glucosidase inhibitors from the leaves of Aegle marmelos. [J].Bioorganic& Medicinal Chemistry Letters,2008,18(18):4956-8
Poitout L, Merrer Y L, Depezay J C. Polyhydroxylated piperidines and azepanes from D-mannitol synthesis of 1-deoxynojirimycin and analogues [J]. Tetrahedron,1994,35(20):3293-3296
Ryu K S, Heui S L, Sun Y K. Pharmacodynamic study of silkworm powder in mice administered to maltose, sucrose and lactose [J]. Serv Sci,1999,41(1):9-13
Ryu K S, Heui S L, Sung H C, et al. An activity of lowering blood-glucose levels according to preparative condition of silkworm powder [J]. Serv Sci, 1997,39(1):79-85
Saudagar P S, Singhal R S. Optimization of Nutritional Requirements and Feeding Strategies for Clavulanic Acid Production by Streptomyces Clavuligerus [J].Bioresour Technol,2007,98(10):2 010-2 017.
Schmidt D D, Frommer W, Muller L, et al. Glucosidase-Inhibitoren aus Bazillen [J]. Naturwissenschaften,1979, 66(11):584-585
Shibano M, Fujimoto U, Kushino K, et al. Biosynthesis of 1-deoxynojirimycin in Commelina communis: a difference between the microorganisms and plants[J]. Phytochemistry, 2004,65(19):2661-2665
Shibano M, Tsukamoto D, Tanaka Y, et al. Determination of 1-deoxynojirimycin and 2,5-dihydroxymethyl 3,4-dihydroxypyrrolidine contents of Commelina communis var. hortensis and the antihyperglycemic activity [J]. Nat Med, 2001,55(5):251-254
Stephen P C,Clive E. Acarbose a preliminary review of its pharmacodynamic and pharmacolinetic properties and therapeutic potential[J].Drugs.1988,35: 214-243
Straub A, Effenberger F, Fischer D. Aldolase-catalyzed C-C bond formation for stereoselective synthesis of nitrogen-containing carbohydrates[J].J Org Chem, 1990,55(12):3926-3932
Strobel GA, Stierle A.Taxomyces andreanae, a proposed new taxon for a Bubilliferous hyphomyces associated with pacific yew(Taxus brevifolia)[J].Mycotaxon,1993,47:71-80.
Tang XJ, He GQ, Chen QH, et al. Medium optimization for the production of thermal stable methodology[J].Bioresource Technology, 2004,93:175-181
Thompson D R, Thompson D R. Response surface experimentation[J]. Food Proc Pres,1982,3(6):155-188
Tierney M, Pottage J, Kessler H, et al. The tolerability and pharmacokinetics of N-butyl-deoxynojirimycin in patients with advanced HIV disease [J].J Acquir Immune Defic Syndr Hum Retrovirol, 1995, 10(5):549-553
Tsutomu Tsuruka, Harumi Fukuyasu. Inhibition of mouse tumor metastasis with nojirimycin-related compounds[J]. Antiboitics,1996,49(2):155-161
Wu HQ, Tian L, Zhang JM, et al. Culture medium optimization for pigment production with RSM method[J].Acta Oceanologica Sinica,2005,27(3):142-146
Wu Q L, Chen T, Gan Y. Optimization of Riboflavin Production by Recombinant Bacillus Subtilis RH44 Using Statistical Designs[J].Appl Microbiol Biotechnol,2007,76(4):783-794.
Yagi M, Kouno T, Aoyagi Y, et al. The structure of moranoline a piperidine alkaloid from Morus species [J]. Nippon Nogeik Kaishi,1976, 50(11):571- 572
Yatsunami K, Ichida M, Onodera S. The relationship between 1-deoxynojirimycin content andα-glucosidase inhibitory activity in leaves of 276 mulberry cultivars (Morus spp.) inKyoto, Japan [J]. Nat Med, 2008, 62(1):63-66
Yin H, Shi X Q, Sun B, et al. Accumulation of 1-deoxynojirimycin (1-DNJ) in silkworm, Bombyx mori L.[J]. J Zhejiang Univ Sci B,2010 ,11(4):286-291
Yoshiaki Y. Inhibition of intestinal a-glucosidase activity and postprandial hyperglycemia by moranoline and its N-alkyl derivatives[J]. Agricultural and Biological Chemistry,1988, 52(1):121-128
Zamir L Q, Zhang J Z, Kutlerer K , et al. 5-Epi-canadensede and other novel metabolites of Taxus Canadensis [J].Tetrahedron, 1998, 54 (52): 15845-15860.
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
陈正收,徐瑾,周应军,等.桑白皮药材中1-脱氧野尻霉素的两种含量测定方法的比较[J].中成药,2007,29(11):1654-1657
陈智毅,吴娱明,陈列辉,等.家蚕对糖尿病小鼠治疗作用的研究[J].广东蚕业,2002,36(2):35-38
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.
褚以文.微生物培养基优化方法及其OPTI优化软件[J].国外医药抗生素分册,1999,20(2):58-60.
戴开金,侯连兵,罗奇志.高效液相色谱-串联四极杆质谱法测定桑叶中1-脱氧野尻霉素[J].中药材,2009, 32(3):375-377
东秀珠,蔡妙英.常见细菌系统鉴定手册[M].科学出版社,2001
樊竹青.α-葡萄糖苷酶抑制剂治疗糖尿病的研究进展综述[J].思茅师范高等专科学校学报, 2005,21(3):3-5
方开泰.均匀试验设计的理论、方法和应用[J].数理统计与管理,2004,3(3):69-88
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,2003,15(6):536.
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):1151-1154
龚波林,耿信笃.单分散交联聚甲基丙烯酸环氧丙酷树脂的制备及亲和纯化伴刀豆球蛋白-A[J].分析化学研究报告,2003,31(8):923-927
顾江萍,梁鑫森.中药对α-葡萄糖苷酶抑制作用的研究[J].中华现代中医学杂志.2005,l(2):45-46
关丽萍,郑光浩,金晴吴,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
桂仲争,戴建一,陈军建,等.全蚕粉的食用价值及其降血糖的临床试验效果[J].蚕业科学,2004,30(1):107-110
胡竟一,雷玲,刘亚欧,等.桑叶的α-葡萄糖苷酶抑制作用研究[J].中药药理与临床, 2006,22(6):44-45
胡瑞君.川麦冬-桑叶降血糖功能性成分提取工艺的研究[D].四川成都:西华大学,硕士毕业论文, 2009
姜永涛,陈继永,刘珂.HPLC-ELSD测定桑叶中1-脱氧野尻霉素的含量[J].药物分析杂志, 2005,25(1):27-29
蒋运刚,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
李凡,裘雅渔,钱文春,等.桑叶中总生物碱和1-脱氧野尻霉素的含量考察[J].中国药学杂志,2008, 43(3):176-179
李英,张兰,杨万山,等.α-葡萄糖苷酶抑制剂的筛选和初步研究[J].上海大学学报(自然科学版),2000,6(2): 129-132
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): 659-661
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
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): 31-33
娄德帅. 1-脱氧野尻霉素(DNJ)生物合成影响因素和富含DNJ分离物对HeLa肿瘤细胞抑制作用的研究[D].江苏镇江:江苏科技大学,硕士学位论文, 2010
卢大胜,雍克岚,陈旭.广西血竭中α-葡萄糖苷酶活性抑制剂有效组分的萃取分离[J].上海大学学报(自然科学版)).2005,11(1): 71-73
陆燕,梅乐和,陆悦飞,等.响应面法优化工程菌产细胞色素P450BM23的发酵条件[J].化工学报,2006,57(5):1 187-1 192.
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
马建标,李建敏,王利民.低交换容量混胺树脂的合成及其对绞股蓝皂的吸附性能[J].高等学校化学学报,1992,13(12):1626-1629
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, 31 (9): 112-114
马庆一,陈春涛,时国庆等.天然α-葡萄糖苷酶抑制剂的研究[J].食品工业科技.2005,26(8): 51-53
孟夏,欧阳臻,常钰,等.不同产地桑叶的1-脱氧野尻霉素含量比较[J].中药材,2008,31(1):8-10
欧阳臻,陈钧.不同季节桑叶中1-脱氧野尻霉素(DNJ)含量的测定[J].食品科学,2004,25(10):211-214
欧阳臻,李永辉,徐卫东,陈钧.高效液相色谱-荧光检测法测定桑叶中1-脱氧野尻霉素(DNJ)含量[J].中国中药杂志, 2005, 30(9): 682-685
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].中国药房,2007,18(1):22-24
全吉淑,伊学哲,金明等.大豆皂苷对α-葡萄糖苷酶抑制作用的研究[J].中药材.2003,26(9): 654-656
沈佳佳,张晓军等.新型抗糖尿病药物-米格列醇的研究进展[J].海峡药学.2005,17(6):8-10
沈以红,朱见,代方银,等.野桑蚕和不同家蚕品系幼虫体内1-脱氧野尻霉素含量测定[J].蚕业科学,2007,33(4):674-677
施新琴,崔为正,裘立群,等.用反相高效液相色谱-紫外检测法测定1-脱氧野尻霉素的含量[J].蚕业科学, 2006,32(1):146-149
施新琴,肖辉,孙波,等.不同全蚕粉中的1-脱氧野尻霉素含量及其对小鼠血糖浓度的影响[J].蚕业科学, 2009,35(1):111-115
孙凌云,孙波,赵春晓,等. 26种昆虫体内的1-脱氧野尻霉素含量测定[J].蚕业科学,2010,36(3):558-563
滕利荣,孟庆繁,刘培源,等.酶法提取百合多糖及其体外氧化活性[J].吉林大学学报,2003,41(4):538-542
田丽丽,李中军,李辉. 1-脱氧氮杂-D-葡萄糖(Deoxynojirimycin, DNJ)的合成[J].应用化学, 2004,21(1): 12-15
王洪伟,崔崇士,徐雅琴.南瓜多糖复合酶法提取及纯化的研究[J].食品科学,2007,28(8):247-249
王鹏,王玉珠,沈建民.均匀设计及其在药学中的应用[J].沈阳药学院学报,1989,6(4):297-305
卫引茂,黄晓冬,陈强.连续棒状弱阳离子交换柱的合成及其对蛋白质保留行为[J].分析化学,2000,28(10):1194-1195
夏平,谢何青.复合酶法提取桑叶中多糖的工艺条件优化[J].安徽农业科学,2009,37(1):198-199
肖辉,施新琴,罗存敏,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
刑辉,李勇,张金芳,等.桑树组织培养物中1-脱氧野尻霉素的产生规律初探[J].蚕业科学.2008,34(2):322-326
许有瑞.甘草中α-葡萄糖苷酶抑制剂的筛选研究[D].甘肃兰州:兰州大学,硕士毕业论文,2006
杨海霞.桑叶中DNJ分离纯化及含量测定的研究[D].浙江杭州:浙江大学,硕士毕业论文, 2003
杨梅.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):121-123
杨雨,欧阳臻,常钰,等.桑叶不同组分降血糖作用研究[J].食品科学,2007, 28(8): 454-456
叶晶晶,殷浩,孙波,等.桑树中1-脱氧野尻霉素含量变化规律研究[J].蚕业科学, 2009,35(4):722-727
叶晶晶.桑树中产1-脱氧野尻霉素微生物的研究[D].山东泰安:山东农业大学,硕士毕业论文,2010
殷浩.桑树和家蚕对DNJ的富集规律及桑籽降血糖作用研究[D].山东泰安:山东农业大学,硕士毕业论文,2009
原爱红,马骏,蒋晓峰,等.桑叶中糖苷酶抑制活性组分的筛选及体外活性研究[J].同济大学学报, 2005,26(4):8-11
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].中华内分泌代谢杂志,2007,23(6):550-552
袁志发,周静芋.试验设计与分析(第二版)[M].高等教育出版社. 2000 张海容,韩伟珍.微波法与传统热水法浸提香菇多糖的比较研究[J].食品研究与开发,2005,26(5):68-71
张金芳.组培桑苗中1-脱氧野尻霉素含量影响因子的研究[D].山东泰安:山东农业大学,硕士毕业论文,2007
张晓臣.气相色谱法测定桑叶中1-脱氧野尻霉素含量的研究[D],陕西杨凌:西北农林科技大学,硕士毕业论文,2007
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
赵前程,滕钊,汪秋宽,刘俊荣,金桥,王翀,白鹤.复合酶法提取海带多糖的研究[J].沈阳农业大学学报,2007,38(2):220-223
周光雄,阮杰武,黄美燕,叶文才,何业伟.蚕沙中生物碱成分研究[J].中药材,2007,30(11):1384-1385
周乐春,魏兆军,张海祥,等.产1-脱氧野尻霉素微生物菌株的筛选与鉴定[J].食品科学, 2009, 30(23): 361-364
朱见.桑叶、蚕体中1-脱氧野尻霉素的含量测定与分析[D].重庆:西南大学,2008
朱建星,魏荣卿,刘晓宁.一种新型胺基树脂的制备[J].过程工程学报,2005,5(1):44-48
Asano N, Kato A, Miyauchi M, et al. Nitrogen-containing furanose and pyranose analogues from Hyacinthus orientalis [J]. Nat Prod, 1998, 61(5):625-628
Asano N, Nishida M, Miyauchi M, et al. Polyhydroxylated pyrrolidine and piperidine alkaloids from Adenophora triphylla var. japonica (Campanulaceae) [J]. Phytochemistry, 2000,53(3):379-387
Asano N, Oseki K, Kaneko E, et al. Enzymic synthesis ofα- andβ-D-glucosides of 1-deoxynojirimycin and their glycosidase inhibitory activities[J]. Carbohydr Res, 1994,258(20):255-266
Asano N, Yamashita T, Yasuda K, et al. Polyhydroxylated alkaloids isolated from mulberry trees (Morus alba L.) and silkworms (Bombyx mori L.) [J]. Food Chem, 2001,49(9):42082-42131
B. Lembcke, U.R. F?lsch, W. Creutzfeldt. Effect of 1-desoxynojirimycin derivatives on small intestinal disaccharidase activities and on active transport in vitro Digestion [J]. Digestion, 1985, 31(2-3):120-127
Barira I,Shahper NK, Irfanul H, et al. Novel anti-adherence activity of mulberry leaves: inhibition of Streptococcus mutans biofilm by 1-deoxynojirimycin isolated from Morus Alba[J].Journal of Antimicrobial Chemotherapy.2008,62(4):751-757
Beaupere D, Stasik B, Vzanet R, et al. Azidation selective du L-sorbose. Application a la synthese rapide de la 1-deoxynojirimycin[J]. Carbohydr Res,1989,191(1):163-166
Beractes R C, Ganem B. Total synthese (+)-castanospermine and (+)-deoxynojirimycin [J]. Tetrahedron,1984,25(2):165-168
Bischoff J, Kornfeld R. The effect of 1-deoxymannojirimycin on rat liver alpha-mannosidases [J]. Biochem Biophys Res Commun, 1984, 125(1):324-331
Chida N, Furuno Y, Ikemoto. et al. Synthesis of (+)- and (-)-nojirimycin and their 1-deoxyderivatives from myoinositol [J]. Carbohydr Res,1992,237(31):185-194
Daniel C, Stein T, Leslie K, et al. Characterization of Bacillus subtilis DSM704 and its production of 1-deoxynojirimycin [J]. Appl Environ Microbiol, 1984,48(2):280-284
Dennis K J, Norman R D. Projection Properties of Placket and Burman design [J]. Technometrics , 1992 , 34(4): 423-425.
Ertola R J, Giulietti A M, Castillo F J. Design, Formulation and Optimization of Media [J]. Bioprocess Technol,1995,21:89-137.
Ezure Y, Maruo S, Myazaki K, et al. Moranoline(1-deoxynojirimycin) fermentation and its improvement [J]. Agric Biol Chem, 1985,49(4):1119-1125
Frommer W, Muller L, Schmidt D D, et al. Inhibitors for glycoside hydrolases from bacilli:German,2658563[P]. 1976-12-23
Gross V, Andus T, Tran-Thi TA, et al. 1-deoxynojirimycin impairs oligosaccharide processing of alpha 1-proteinase inhibitor and inhibits its secretion in primary cultures of rat hepatocytes [J]. Biological Chemistry, 1983,258(20):12203-12209
Han J, Inoue S, Isoda H, et al. Effects of silkworm powder on glucose absorption by human intestinal epithelial cell line Caco-2[J]. Nat Med, 2007,61(4):387-390
Hardick D J, Hutchinson D W, Trew S J, et al. The biosynthesis of deoxynojirimycin and deoxymannojirimycin in Streptomyces subrutilus[J]. Chem Commun, 1991, 729-730
Hardick D J, Hutchinson D W, Trew S J, et al. Glucose is a precursor of 1-deoxynojirimycin and 1-deoxymannonojirimycin in Streptomyces subrutilus[J]. Tetrahedron, 1992,48(30):6285-6296
Hardick D J, Hutchinson D W. The biosynthesis of 1-deoxynojirimycin in Bacillus subtilis var. niger [J]. Tetrahedron, 1993,49(30):6707-6716
Inouye S, Tsuruoka T, Ito T, et al. Structure and synthesis of nojirimycin [J]. Tetrahedron,1967, 24(5):2125-2144
Jon L, Anita T, Linda J, et al. Isolation and characterization of galactoglu comannan from spruce[J]. Carbohyd Polym,2002,48(11):29-39
Jong-Anurakkun N, Bhandari M R, Hong G, et al.α-Glucosidase inhibitor from Chinese aloes[J].Fitoterapia,2008,79(6):456-457.
Kim HS, Kim YH, Hong YS. et al.α-Glucosidase inhibitors from Commelina communis [J]. Planta Med, 1999, 65(5):437-439
Kim J W, Kim S U, Lee H S, 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
Kimura T, Nakagawa K, Kubota H, et al. Food-grade mulberry powder enriched with 1-deoxynojirimycin suppresses the elevation of postprandial blood glucose in humans [J]. J Agric Food Chem, 2007, 55:5869-5874.
Kinast G, Schedel M. Production of N-substituted derivatives of 1-deoxy-nojirimycin: United States,4266025[P]. 1981-05-05
Koji D, Yoshihiko I, Tsunematsu T. Studies on the constituents of the water extract of the root of mulberry tree (Morus bombycis Koidz) [J]. Chem Pharm Bull,1986,34(5):2243-2246
Lee SS, Lin HC, Chen CK. Acylated flavonol monorhamnosides,α-glucosidase inhibitors, from Machilus philippinensis [J].Phytochemistry,2008,69(12):2347-2353.
Lembcke B, F?lsch U R, Creutzfeldt W. Effect of 1-desoxynojirimycin derivatives on small intestinal disaccharidase activities and on active transport in vitro digestion [J]. Digestion, 1985, 31(2/3):120-127
Li C, Bai JH, Cai ZL, et al. Culture medium optimization and primary kinetics analysis for nisin production[J]. Chinese Journal of Biotechnology,2001,17(2):187-192
Makio S, Koji K, Masahiko T, et al. Antioxidant constituents in the dayflower (Commelina communis L.) and theirα-glucosidase-inhibitory activity [J]. Nat Med, 2008,62(3):349-353
Maruo S, Yamashita H, Miyazaki K, et al. A novel and efficient method for enzymatic synthesis of high purity maltose using moranoline (1-deoxynojirimyein) [J]. BiosBiotechnol Biochem, 1992,56(9):1406-1409
Matsumura S, Enomoto H, Aoyagi Y, et al. Moranoline derivatives and process for preparation thereof:United States,4338433[P]. 1982-07-06
Murao S, Miyata S. Isolation and characterization of a new trehalase inhibitor S-GI [J]. Agric Biol Chem, 1980, 44(1):219-221
Nitra N, Kornkanok I, Wiroje K, et al. Quantitative determination of 1-deoxynojirimycin in mulberry leaves using liquid chromatography-tandem mass spectrometry [J]. J Pharm Biomed Anal, 2007, 44:853-858
Oku T, Yamada M, Nakamura M, et al. Inhibitory effects of extractives from leaves of Morus alba on human and rat small intestinal disaccharidase activity[J]. Nutrition, 2006, 95(5):933-938.
Paulsen H, Sangster I, Heyns K. Syntheses and reaktionen von keto-piperdinosen[J]. Chem Ber, 1969, 100:802-1001
Phuwapraisirisan P, Puksasook T, Jong-aramruang J, et al. Phenylethyl cinnamides: A new series ofα-glucosidase inhibitors from the leaves of Aegle marmelos. [J].Bioorganic& Medicinal Chemistry Letters,2008,18(18):4956-8
Poitout L, Merrer Y L, Depezay J C. Polyhydroxylated piperidines and azepanes from D-mannitol synthesis of 1-deoxynojirimycin and analogues [J]. Tetrahedron,1994,35(20):3293-3296
Ryu K S, Heui S L, Sun Y K. Pharmacodynamic study of silkworm powder in mice administered to maltose, sucrose and lactose [J]. Serv Sci,1999,41(1):9-13
Ryu K S, Heui S L, Sung H C, et al. An activity of lowering blood-glucose levels according to preparative condition of silkworm powder [J]. Serv Sci, 1997,39(1):79-85
Saudagar P S, Singhal R S. Optimization of Nutritional Requirements and Feeding Strategies for Clavulanic Acid Production by Streptomyces Clavuligerus [J].Bioresour Technol,2007,98(10):2 010-2 017.
Schmidt D D, Frommer W, Muller L, et al. Glucosidase-Inhibitoren aus Bazillen [J]. Naturwissenschaften,1979, 66(11):584-585
Shibano M, Fujimoto U, Kushino K, et al. Biosynthesis of 1-deoxynojirimycin in Commelina communis: a difference between the microorganisms and plants[J]. Phytochemistry, 2004,65(19):2661-2665
Shibano M, Tsukamoto D, Tanaka Y, et al. Determination of 1-deoxynojirimycin and 2,5-dihydroxymethyl 3,4-dihydroxypyrrolidine contents of Commelina communis var. hortensis and the antihyperglycemic activity [J]. Nat Med, 2001,55(5):251-254
Stephen P C,Clive E. Acarbose a preliminary review of its pharmacodynamic and pharmacolinetic properties and therapeutic potential[J].Drugs.1988,35: 214-243
Straub A, Effenberger F, Fischer D. Aldolase-catalyzed C-C bond formation for stereoselective synthesis of nitrogen-containing carbohydrates[J].J Org Chem, 1990,55(12):3926-3932
Strobel GA, Stierle A.Taxomyces andreanae, a proposed new taxon for a Bubilliferous hyphomyces associated with pacific yew(Taxus brevifolia)[J].Mycotaxon,1993,47:71-80.
Tang XJ, He GQ, Chen QH, et al. Medium optimization for the production of thermal stable methodology[J].Bioresource Technology, 2004,93:175-181
Thompson D R, Thompson D R. Response surface experimentation[J]. Food Proc Pres,1982,3(6):155-188
Tierney M, Pottage J, Kessler H, et al. The tolerability and pharmacokinetics of N-butyl-deoxynojirimycin in patients with advanced HIV disease [J].J Acquir Immune Defic Syndr Hum Retrovirol, 1995, 10(5):549-553
Tsutomu Tsuruka, Harumi Fukuyasu. Inhibition of mouse tumor metastasis with nojirimycin-related compounds[J]. Antiboitics,1996,49(2):155-161
Wu HQ, Tian L, Zhang JM, et al. Culture medium optimization for pigment production with RSM method[J].Acta Oceanologica Sinica,2005,27(3):142-146
Wu Q L, Chen T, Gan Y. Optimization of Riboflavin Production by Recombinant Bacillus Subtilis RH44 Using Statistical Designs[J].Appl Microbiol Biotechnol,2007,76(4):783-794.
Yagi M, Kouno T, Aoyagi Y, et al. The structure of moranoline a piperidine alkaloid from Morus species [J]. Nippon Nogeik Kaishi,1976, 50(11):571- 572
Yatsunami K, Ichida M, Onodera S. The relationship between 1-deoxynojirimycin content andα-glucosidase inhibitory activity in leaves of 276 mulberry cultivars (Morus spp.) inKyoto, Japan [J]. Nat Med, 2008, 62(1):63-66
Yin H, Shi X Q, Sun B, et al. Accumulation of 1-deoxynojirimycin (1-DNJ) in silkworm, Bombyx mori L.[J]. J Zhejiang Univ Sci B,2010 ,11(4):286-291
Yoshiaki Y. Inhibition of intestinal a-glucosidase activity and postprandial hyperglycemia by moranoline and its N-alkyl derivatives[J]. Agricultural and Biological Chemistry,1988, 52(1):121-128
Zamir L Q, Zhang J Z, Kutlerer K , et al. 5-Epi-canadensede and other novel metabolites of Taxus Canadensis [J].Tetrahedron, 1998, 54 (52): 15845-15860.