CN110279731A - 一种白檀提取物在制备降低血糖的食品、药品或保健品中的应用 - Google Patents
一种白檀提取物在制备降低血糖的食品、药品或保健品中的应用 Download PDFInfo
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- CN110279731A CN110279731A CN201910665175.7A CN201910665175A CN110279731A CN 110279731 A CN110279731 A CN 110279731A CN 201910665175 A CN201910665175 A CN 201910665175A CN 110279731 A CN110279731 A CN 110279731A
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Classifications
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
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- A—HUMAN NECESSITIES
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- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
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- A—HUMAN NECESSITIES
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- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
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- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
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Abstract
本发明提供一种白檀提取物在制备降低血糖的食品、药品或保健品中的应用,涉及生物技术领域,本发明提供了一种白檀提取物在制备降低血糖的食品、药品或保健品中的应用,所述白檀提取物为白檀的水提取物或醇提取物。本发明所述白檀提取物是一种纯天然、植物源的提取物,对α‑淀粉酶、蔗糖酶以及麦芽糖酶活性均有抑制作用,制备成本低,副作用相对于西药较小。本发明的实验表明,本发明提供的白檀提取物能够有效降低正常小鼠和糖尿病小鼠的餐后血糖。
Description
技术领域
本发明涉及生物技术领域,尤其涉及一种白檀提取物在制备降低血糖的食品、药品或保健品中的应用。
背景技术
糖尿病(diabetes mellitus,DM)是由遗传和环境因素相互作用而引起的以持续高血糖为特征的慢性代谢性疾病,已成为影响全球居民健康的主要慢性非传染性疾病之一,其患病率呈逐年上升趋。国际糖尿病联盟(International Diabetes Federation,IDF)估计,全球有4.25亿人患有糖尿病,到2045年,这一数字预计将达到近7亿。持续高血糖是糖尿病的主要表型并随时间的推移导致严重的糖尿病并发症,包括冠状动脉疾病,中风,外周动脉疾病,视网膜病变,肾病和神经病变。现代药理研究表明,几乎所有Ⅱ型糖尿病都要经过葡萄糖耐量缺损(impaired glucose tolerance,IGT)阶段,IGT的主要临床特征表现为餐后高血糖。研究认为餐后高血糖是引起糖尿病人大血管并发症和微血管并发症的重要因素,而这些并发症是引起糖尿病死亡率增大的一个主要原因。利用α-葡萄糖苷酶抑制剂抑制人淀粉酶以及人小肠α-葡萄糖苷酶的活性,将餐后血糖(postprandialblood glucose,PBG)水平保持接近正常范围,是控制血糖波动,治疗和预防糖尿病及其并发症的重要方法。
目前,中国国内DM药物市场中应用的α-葡萄糖苷酶抑制剂主要有阿卡波糖(acarbose),伏格列波糖(voglibose)和米格列醇(miglitol),它们都能够通过抑制体内糖苷酶的活性,减少淀粉和寡糖的降解,减少葡萄糖的产生以及延缓葡萄糖的吸收入血来实现其降低餐后高血糖的药效活性。阿卡波糖主要通过抑制淀粉酶及蔗糖酶的活性,抑制淀粉和蔗糖的分解起到降糖作用的。米格列醇和伏格列波糖主要是通过抑制蔗糖酶及麦芽糖苷酶的活性,减少蔗糖和麦芽糖的进一步的水解来起到降糖作用的。但是他们的价格较贵,对于多数长期服药的糖尿病患者,经济压力较大,并且有腹泻,腹部绞痛,胀气和呕吐等副作用。因此,从天然植物资源中,寻找和发现具有抑制α-葡糖苷酶的天然成分及其潜在的成药化合物,并开发成安全、高效的降血糖天然药物具有重要学术价值和社会意义。
白檀(Symplocospaniculata)为山矾科(Symplocaceae)山矾属植物(Symplocos),落叶灌木或小乔木。俗称碎米子树、乌子树,其味辛、性温、无毒。传统中医理论认为白檀根、叶、花或种子均可入药,具有清热、解毒、消肿等功能,对乳腺炎、淋巴腺炎、肠痈、皮肤瘙痒等病症有一定疗效。国内外学者通过调查、走访、研究分析,了解到白檀全株均具有较高的药用价值。目前国内外学者关于白檀的化学成分和药理活性报道较少。Na等(Planta.Med.2016,72(3)261-263)分离提取了白檀茎叶的活性成分并得出白檀茎叶中含有预防糖尿病和肥胖病等慢性疾病的成分。Semwal等(Journal ofEthnopharmacology,2011,135:78-87)发现白檀树皮中相关化学成分具有显著抗菌、镇痛、抗炎活性。王宁辉等(时珍国医国药,2014,25(11),2624-2626)报道了白檀中抗氧化活性成分。目前没有关于白檀的粗提取物具有降血糖作用的报道。
发明内容
本发明为了克服现有降糖药物价格昂贵且副作用较大的缺陷,提供了一种白檀提取物在制备降低血糖的食品、药品或保健品中的应用,白檀提取物可通过抑制α-淀粉酶、蔗糖酶以及麦芽糖酶活性的途径显著降低餐后血糖。
为了实现上述发明目的,本发明提供以下技术方案:
本发明提供了一种白檀提取物在制备降低血糖的食品、药品或保健品中的应用,所述白檀提取物为白檀的水提取物或醇提取物。
优选的,所述白檀提取物的制备方法包括以下步骤:
将白檀的茎粉碎,获得白檀茎粉,以体积浓度90%以上的乙醇水溶液或水对所述白檀茎粉进行超声提取后,固液分离,收集液相组分干燥,得到白檀提取物。
优选的,粉碎后得到的白檀茎粉的质量与所述乙醇水溶液或水的体积之比为1g:5~10ml。
优选的,所述超声提取的温度为35~50℃,超声提取的时间为1.5~4h,超声提取的频率为18~25kHz。
优选的,所述超声提取的次数为1~3次。
优选的,所述白檀提取物抑制α-淀粉酶、蔗糖酶和麦芽糖酶的活性而降低血糖。
优选的,所述食品、药品或保健品的剂型包括片剂、口服液、颗粒剂、注射剂、贴剂、膏剂、粉剂、栓剂和胶囊剂。
优选的,所述食品、药品或保健品中,白檀提取物的质量百分浓度为0.1~99.9%。
优选的,所述食品、药品或保健品中还包括辅料。
与现有技术相比,本发明的有益效果:
(1)本发明提供了白檀的水提取物或醇提取物在制备降血糖的食品、药品或保健品中的应用,所述白檀提取物是一种纯天然、植物源的提取物,制备成本低,副作用相对于西药较小。
(2)本发明的实验表明,本发明提供的白檀提取物能够有效降低正常小鼠和糖尿病小鼠的餐后血糖。
(3)本发明的实验表明,本发明提供的白檀提取物对α-淀粉酶、蔗糖酶以及麦芽糖酶活性均有抑制作用,进而降低糖的分解量,达到显著降低餐后血糖的目的。
附图说明
图1为实施例4中白檀提取物和阿卡波糖降低餐后血糖效果图;其中,图1A为白檀提取物和阿卡波糖对正常小鼠餐后血糖的影响,图1B为白檀提取物和阿卡波糖对糖尿病小鼠餐后血糖的影响;
图2为实施例4中不同浓度下阿卡波糖和白檀提取物α-葡萄糖苷酶抑制活性IC50值;其中,A阳性药阿卡波糖α-葡萄糖苷酶抑制活性IC50值;B白檀醇提物α-葡萄糖苷酶抑制活性IC50值;C白檀水提物α-葡萄糖苷酶抑制活性IC50值;
图3为实施例4中不同浓度下阿卡波糖和白檀提取物α-淀粉酶抑制活性IC50值;其中,A阳性药阿卡波糖α-淀粉酶抑制活性IC50值;B白檀醇提物α-淀粉酶抑制活性IC50值;C白檀水提物α-淀粉酶抑制活性IC50值;
图4为实施例4中不同浓度下阿卡波糖和白檀提取物蔗糖酶抑制活性IC50值;其中,A阳性药阿卡波糖蔗糖酶抑制活性IC50值;B白檀醇提物蔗糖酶抑制活性IC50值;C白檀水提物蔗糖酶抑制活性IC50值;
图5为实施例4中不同浓度下阿卡波糖和白檀提取物麦芽糖酶抑制活性IC50值;其中,A阳性药阿卡波糖麦芽糖酶抑制活性IC50值;B白檀醇提物麦芽糖酶抑制活性IC50值;C白檀水提物麦芽糖酶抑制活性IC50值;。
具体实施方式
本发明提供了一种白檀提取物在制备降低血糖的食品、药品或保健品中的应用,所述白檀提取物为白檀的水提取物或醇提取物。
具体的,本发明所述白檀提取物的制备方法包括以下步骤:
将白檀的茎粉碎,获得白檀茎粉,以体积浓度90%以上的乙醇水溶液或水对所述白檀茎粉进行超声提取后,固液分离,收集液相组分干燥,得到白檀提取物。
本发明根据藏药志记载,从中选取具有治疗止渴、脾虚、肾虚或是肺热功能的中药和藏药材,对其水提物进行α-淀粉酶,麦芽糖酶和蔗糖酶抑制活性研究,以期发现潜在α-葡糖苷酶抑制剂天然产物来源。在本发明中,所述粉碎的粒径优选为80~150目,更优选为100目。
在本发明中,粉碎后得到的白檀茎粉的质量与所述乙醇水溶液或水的体积之比优选为1g:5~10ml,更优选为1g:6~8ml。在本发明中,所述乙醇水溶液的体积浓度优选为95%。
在本发明中,所述提取包括但不限于超声提取,还可以采用其他提取方式,例如加热提取。超声提取的方式更为便捷。在本发明中,所述超声提取的温度优选为35~50℃,更优选为40℃;所述超声提取的时间优选为1~5h,更优选为2~3h;所述超声提取的频率优选为18~25kHz,更优选为20kHz。在本发明中,所述超声提取的次数优选为1~3次。
本发明对所述固液分离的方法没有特殊限定,采用本领域已知的固液分离方法即可,例如离心或过滤。
在本发明中,所述白檀提取物可以作为α-淀粉酶、蔗糖酶和麦芽糖酶的酶活抑制剂,进而降低体内血糖含量。
在本发明中,所述降血糖的食品、药品或保健品的剂型包括但不限于片剂、口服液、颗粒剂、注射剂、贴剂、膏剂、粉剂、栓剂和胶囊剂。在本发明中,所述食品、药品或保健品中,白檀提取物的质量百分浓度优选为0.1~99.9%,更优选为1~95%。在本发明中,所述食品、药品或保健品中优选的还包括辅料,本发明对具体的辅料种类和用量无特殊限定,根据不同剂型进行选择和确定即可。
下面结合实施例对本发明提供的技术方案进行详细的说明,但是不能把它们理解为对本发明保护范围的限定。
实施例1
将干燥的白檀茎粉碎至100目,得到白檀茎粉;将白檀茎粉与水按照1g:8ml的比例混合,在40℃、20kHz的条件下超声提取2次,每次提取2h,合并每次提取的上清液,得到白檀水提取物。
实施例2
将干燥的白檀茎粉碎至100目,得到白檀茎粉;将白檀茎粉与95%乙醇水溶液按照1g:7ml的比例混合,在40℃、20kHz的条件下超声提取2次,每次提取2h,合并每次提取的上清液,得到白檀醇提取物。
实施例3
将干燥的白檀茎粉碎至80目,得到白檀茎粉;将白檀茎粉与水按照1g:9ml的比例混合,在42℃、22kHz的条件下超声提取3次,每次提取2.5h,合并每次提取的上清液,得到白檀水提取物。
实施例4
1、实验材料和实验仪器
实验材料:
受试药物:实施例1制备的白檀水提取物和实施例2制备的白檀醇提取物。
动物:KM小鼠。
试剂:麦芽糖、蔗糖和阿卡波糖,Solaibio公司;α-葡萄糖苷酶(来源于酵母菌)和猪胰腺α-淀粉酶,爱尔兰Megazyme公司,葡萄糖,上海麦克林生化科技有限公司,p-NPG(4-Nitrophenyl glucopyranoside,纯度>98%),美国Sigma公司;淀粉,广州天骏生物科技有限公司。
实验仪器:H1850R低温离心机(湖南湘仪离心机仪器有限公司),Epoch2酶标仪(BioTek公司),BE9010恒温振荡器(海门市其林贝尔仪器制造有限公司),CTXNW-100B循环超声提取机(北京弘祥隆生物技术开发有限公司),N-1210BV-WB旋转蒸发仪(上海爱朗仪器有限公司),天平(奥豪斯仪器有限公司),FDU-1100冷冻干燥机(埃朗科技国际(上海)有限公司),PTA-125纯水仪(成都沛斯特科技有限公司)。
2、白檀提取物降低糖尿病小鼠PGB药效研究
(1)白檀两种提取物在正常小鼠体内降血糖作用
分别取40只正常小鼠,分为4组,每组10只小鼠。分别按照以下方式进行给药:
对照组(Control):每只小鼠灌胃纯净水;
阳性对照组(Acarbose):每只小鼠按照4mg/kg灌胃阿卡波糖;
试验组1(ST):每只小鼠按照400mg/kg灌胃白檀水提取物;
试验组2(CT):每只小鼠按照400mg/kg灌胃白檀醇提取物。
给药后各组小鼠分别按照2g/kg灌胃蔗糖,分别在蔗糖灌胃之后0,30,60,90和120min时检测血糖水平(图1A)。
结果如图1A所示,对照组的血糖水平在30分钟达到峰值然后下降。与对照组相比,400mg/kg白檀水提取物或白檀醇提取物和4mg/kg阿卡波糖组小鼠的血糖水平降低,但三组间差异不显着。上述结果表明白檀提取物具有控制餐后血糖水平升高的能力。
(2)白檀两种提取物在正常小鼠体内降血糖作用
构建糖尿病小鼠模型按照Zhao等的方法进行四氧嘧啶诱导(Zhao,X.;Tao,J.;Zhang,T.;Jiang,S.;Wei,W.;Han,H.;Shao,Y.;Zhou,G.YueH.L.ResveratrolosideAlleviates Postprandial Hyperglycemia in Diabetic Mice byCompetitively Inhibiting a-Glucosidase.J.Agric.Food Chem)。
分别取40只糖尿病小鼠,分为4组,每组10只小鼠。分别按照以下方式进行给药:
对照组(Control):每只小鼠灌胃纯净水;
阳性对照组(Acarbose):每只小鼠按照4mg/kg灌胃阿卡波糖;
试验组1(ST):每只小鼠按照400mg/kg灌胃白檀水提取物;
试验组2(CT):每只小鼠按照400mg/kg灌胃白檀醇提取物。
给药后各组小鼠分别按照2g/kg灌胃蔗糖,分别在蔗糖灌胃之后0,30,60,90和120min时检测血糖水平(图1B)。
结果如图1B所示,与对照组相比,400mg/kg白檀水提取物或白檀醇提取物和4mg/kg阿卡波糖组小鼠的餐后血糖水平显著降低(p<0.001)。结果有力地证实了白檀提取物具有降低小鼠餐后血糖水平能力。
3、白檀提取物α-淀粉酶及蔗糖酶和麦芽糖酶抑制活性研究
以阿卡波糖作为阳性对照,分别研究了白檀提取物和水提取物对α-葡萄糖苷酶(来源于酵母菌),蔗糖酶(来源于大鼠小肠),麦芽糖酶(来源于大鼠小肠)和α-淀粉酶(来源于猪胰)的抑制活性。
(1)α-葡萄糖苷酶抑制活性研究,在冰浴条件下,在96孔板里加入50μL5mg·mL-1的样品和50uL 0.5U mL-1的酶液,放入37℃恒温振荡器,100r min-1孵育10min,再在冰浴的条件下加入50uL 0.5mmol mL-1的p-NPG,然后放入37℃恒温振荡器,100r/min孵育20min,立即投入冰水浴5min,降低酶活性,继续加入0.1mol L-1Na2CO3溶液50μL终止反应。在409nm的波长下检测,并计算样品对酶的抑制活性。
(2)蔗糖酶和麦芽糖酶抑制活性研究:α-葡萄糖苷酶(麦芽糖酶,EC3.2.1.20;蔗糖酶,EC 3.2.1.48)抑制活性筛选:将50μL含有17.5U/mL的酶液和50μL 5mg/mL样品加入48孔板,在37℃下预孵育10min。然后,加入50μL 0.5mol/L蔗糖溶液,将该混合物在37℃下温育20min。立即投入冰水浴5min,降低酶活性,继续加入0.1mol/LNa2CO3溶液50uL终止反应。采用葡萄糖试剂盒测定葡萄糖浓度,并计算样品对蔗糖酶的抑制活性。
将50μL含有11.56U/mL的酶液和50μL 5mg/mL样品加入48孔板,在37℃下预孵育10min。然后,加入50μL 1.39mmol/mL麦芽糖溶液,将该混合物在37℃下温育20min。立即投入冰水浴5min,降低酶活性,继续加入0.1mol/LNa2CO3溶液50uL终止反应。采用葡萄糖试剂盒测定葡萄糖浓度,并计算样品对麦芽糖酶的抑制活性。
(3)α-淀粉酶抑制活性研究:在冰浴的条件下,向96孔板里加入50μL5mg/mL的样品和50μL 10U/mL的酶液,然后放入37℃恒温振荡器,100r/min孵育10min,再在冰浴的条件下加入50μL 0.1%(w/v)的淀粉,然后后放入37℃恒温振荡器,100r/min孵育20min,立即投入冰水浴5min,降低酶活性,继续加入100μL DNS溶液,100℃下反应5min。降至常温后在540nm的波长下检测,并计算样品对酶的抑制活性。
白檀醇提取物在浓度5mg/mL下对α-葡萄糖苷酶(来源于酵母菌),α-淀粉酶(来源于猪胰),蔗糖酶和麦芽糖酶的抑制率分别为97.7%,93.5%,73.0%和90.3%。白檀水提取物在浓度5mg/mL下对α-葡萄糖苷酶(来源于酵母菌),α-淀粉酶(来源于猪胰),蔗糖酶和麦芽糖酶的抑制率分别为95.6%,98.4%,88.9%和93.9%。由以上结果可知白檀醇或水提取物均具有很强的α-淀粉酶,蔗糖酶和麦芽糖酶抑制活性,结果见表1和图2~图5。
表1白檀提取物(mg/mL)对多种来源α-葡萄糖苷酶和α-淀粉酶抑制活性
实施例5含有白檀提取物的降血糖软胶囊
将实施例1制备的白檀提取物80份、DHA 10份和维生素E 10份混合,均匀制成软胶囊内容物料,然后将软胶囊内容物料和软胶囊壳料在压制设备上进行压囊处理制成白檀提取物软胶囊。
以上所述仅是本发明的优选实施方式,应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以做出若干改进和润饰,这些改进和润饰也应视为本发明的保护范围。
Claims (10)
1.一种白檀提取物在制备降低血糖的食品、药品或保健品中的应用,其特征在于,所述白檀提取物为白檀的水提取物或醇提取物。
2.根据权利要求1所述的应用,其特征在于,所述白檀提取物的制备方法包括以下步骤:
将白檀的茎粉碎,获得白檀茎粉,以体积浓度90%以上的乙醇水溶液或水对所述白檀茎粉进行超声提取后,固液分离,收集液相组分干燥,得到白檀提取物。
3.根据权利要求2所述的应用,其特征在于,所述白檀茎粉的质量与所述乙醇水溶液或水的体积之比为1g:5~10ml。
4.根据权利要求2所述的应用,其特征在于,所述提取包括超声提取。
5.根据权利要求4所述的应用,其特征在于,所述超声提取的温度为35~50℃,所述超声提取的时间为1.5~4h,所述超声提取的频率为18~25kHz。
6.根据权利要求4所述的应用,其特征在于,所述超声提取的次数为1~3次。
7.根据权利要求1~6任意一项所述的应用,其特征在于,所述白檀醇提取物通过抑制α-淀粉酶,蔗糖酶和麦芽糖酶活性降低餐后血糖。
8.根据权利要求1~6任意一项所述的应用,其特征在于,所述食品、药品或保健品的剂型包括片剂、口服液、颗粒剂、注射剂、贴剂、膏剂、粉剂、栓剂和胶囊剂。
9.根据权利要求1~6任意一项所述的应用,其特征在于,所述食品、药品或保健品中,白檀提取物的质量百分浓度为0.1~99.9%。
10.根据权利要求8所述的应用,其特征在于,所述食品、药品或保健品中还包括辅料。
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MINKYUN NA等: "Inhibition of protein tyrosine phosphatase 1B by ursane-type triterpenes isolated from Symplocos paniculata", 《PLANTA MED》 * |
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