CN107582587A - 一种白凤菜总黄酮提取物及其制备方法与治疗非酒精性脂肪肝的用途 - Google Patents
一种白凤菜总黄酮提取物及其制备方法与治疗非酒精性脂肪肝的用途 Download PDFInfo
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Abstract
本发明属于药品或保健品领域，具体涉及一种白凤菜总黄酮提取物及其制备方法与治疗非酒精性脂肪肝的用途。该提取物中，以重量百分含量计，含有80～85％的芦丁。药效实验结果表明，该提取物对非酒精性脂肪肝有较好的治疗作用，可显著改善非酒精性脂肪肝大鼠的血脂紊乱及脂肪变性，因此可以作为潜在的治疗非酒精性脂肪肝的药物；本发明白凤菜总黄酮提取物的制备方法，在提取步骤后，通过选择特定组成、特定配比的酶组成的复合酶进行酶解，进一步通过大孔树脂萃取浓缩和大孔树脂分离纯化步骤，使得制备得到的白凤菜总黄酮提取物中芦丁的HPLC纯度可达80～85％。
Description
技术领域
本发明属于药品或保健品领域，具体涉及一种白凤菜总黄酮提取物及其制备方法与治疗非酒精性脂肪肝的用途。
背景技术
非酒精性脂肪肝(NAFLD)是一种无过量饮酒史，由多种原因导致的以肝细胞脂肪变性和脂质沉积为特征的临床病理综合征，主要包括单纯性脂肪肝及脂肪性肝炎，后者可以进展为肝纤维化和肝硬化。目前，在全球普通人群中非酒精性脂肪性肝病患病率高达20％～30％，世界范围内超过一半的人将有发生非酒精性脂肪性肝病的危险，明显超过乙型肝炎、丙型肝炎及酒精性肝病的发病率，已成为最常见的肝病。流行病学调查显示NAFLD已成为我国常见的慢性肝病之一，在上海、广州和香港等发达地区成人患病率达10％～25％，且渐趋低龄化。脂肪肝可在短期内发展为不可逆的肝损伤，其纤维化的发生率高达25％，且约有10％的患者会发展为肝硬化，严重威胁国人的健康。目前，对NAFLD的治疗临床上尚缺乏疗效确切的特效药。因此，研发治疗非酒精性脂肪肝的药物已成为研究的热点。
白凤菜(Gynura formosana Kitam.)是菊科菊三七属多年生草本植物，又名白背天葵、片仔癀草，其含有丰富的维生素、生物碱类以及黄酮类物质，是一种药食两用的植物。研究表明，白凤菜主要用于肺炎、肺癌、肝炎、肝硬化、高血压等疾病的治疗，其还有解热解毒的功效。现有技术中，有文献报道了：白凤菜醇提物对非酒精性脂肪肝大鼠具有治疗作用。
然而，目前，现有技术中尚没有白凤菜水提物可以治疗非酒精性脂肪肝的相关报道。
发明内容
为此，本发明提供一种白凤菜总黄酮提取物，进而提供其制备方法与用途。
为解决上述技术问题，本发明是通过以下技术方案来实现的：
本发明提供一种白凤菜总黄酮提取物，以重量百分含量计，含有80～85％的芦丁。
本发明还提供一种上述白凤菜总黄酮提取物的制备方法，包括以下步骤：
(1)提取：取白凤菜加入提取溶剂进行提取，调节提取液的pH值为4- 8，得反应液；
(2)酶解：然后向反应液中加入复合酶进行酶解，30-50℃强制循环反应1-4小时，抽滤，收集滤液；
(3)萃取、浓缩：将滤液用大孔树脂A进行萃取，合并萃取液，将萃取液浓缩，得浓缩液；
(4)分离、纯化：将浓缩液离心，取上清液用大孔树脂B分离纯化，在波长为510nm下测定吸光度，收集洗脱液，浓缩、干燥，即得。
优选地，上述白凤菜总黄酮提取物的制备方法，所述酶解步骤中，采用由木瓜蛋白酶、纤维素酶和果胶酶组成的复合酶进行酶解。
进一步优选地，上述白凤菜总黄酮提取物的制备方法，所述复合酶与所述白凤菜的重量之比为：1:5～1:3。
进一步优选地，白凤菜总黄酮提取物的制备方法，所述复合酶中，木瓜蛋白酶、纤维素酶和果胶酶三者的重量比为(0.5-1.5)：(2-5)：(1-3)；
进一步优选地，上述白凤菜总黄酮提取物的制备方法，所述复合酶中，木瓜蛋白酶、纤维素酶和果胶酶三者的重量比为1：3：2。
进一步优选地，上述白凤菜总黄酮提取物的制备方法，
所述大孔树脂A选自AB-8、DM-130、HZ841、ZH-00、ZH-01、ZH-02、 ZH-03、CAD-40、CAD-45、BS-30中的至少一种；
所述大孔树脂B选自D-101、D-140、D-141、XAD-3、XAD-4、HP-20、 HP-21、LD-605、LSA-10中的至少一种。
进一步优选地，上述白凤菜总黄酮提取物的制备方法，所述提取步骤中，提取溶剂为水，所述白凤菜与所述水的重量之比为1：(20-60)。
进一步优选地，上述白凤菜总黄酮提取物的制备方法，所述分离、纯化步骤中，洗脱溶剂为体积浓度为70-80％的乙醇水溶液，洗脱速度为3-15m/h。
进一步优选地，上述白凤菜总黄酮提取物的制备方法，所述分离、纯化步骤中，洗脱溶剂为体积浓度为75％的乙醇水溶液，洗脱速度为5m/h。
进一步优选地，上述白凤菜总黄酮提取物的制备方法，所述浓缩液中，白凤菜总黄酮的浓度为0.5mg/mL。
进一步优选地，上述白凤菜总黄酮提取物的制备方法，所述萃取、浓缩步骤中，将滤液加入至盛有大孔树脂A的提取罐中，在30℃、80-150rpm下搅拌6-24小时，过滤，以大孔树脂A的重量计，取吸附后的大孔树脂A加入10-30重量倍量的体积浓度为70-95％的乙醇溶液，然后在30℃、80- 150rpm下搅拌6-24小时，过滤，即得萃取液。
进一步优选地，上述白凤菜总黄酮提取物的制备方法，所述提取步骤中，采用盐酸或氢氧化钠调节提取液的pH值为4-8。
进一步优选地，上述白凤菜总黄酮提取物的制备方法，所述干燥为冷冻干燥。
本发明还提供上述制备方法制备得到的白凤菜总黄酮提取物。
本发明还提供一种药物制剂，以上述白凤菜总黄酮提取物、或者上述制备方法制备得到的白凤菜总黄酮提取物为活性成分，按照常规工艺，加入常规辅料制成临床上可接受的片剂、胶囊剂、散剂、合剂、丸剂、颗粒剂、糖浆剂、贴膏剂、栓剂、气雾剂、软膏剂或注射剂。
所述常规辅料为：填充剂、崩解剂、润滑剂、助悬剂、粘合剂、甜味剂、矫味剂、防腐剂、基质等。填充剂包括：淀粉、预胶化淀粉、乳糖、甘露醇、甲壳素、微晶纤维素、蔗糖等；崩解剂包括：淀粉、预胶化淀粉、微晶纤维素、羧甲基淀粉钠、交联聚乙烯吡咯烷酮、低取代羟丙纤维素、交联羧甲基纤维素纳等；润滑剂包括：硬脂酸镁、十二烷基硫酸钠、滑石粉、二氧化硅等；助悬剂包括：聚乙烯吡咯烷酮、微晶纤维素、蔗糖、琼脂、羟丙基甲基纤维素等；粘合剂包括，淀粉浆、聚乙烯吡咯烷酮、羟丙基甲基纤维素等；甜味剂包括：糖精钠、阿斯帕坦、蔗糖、甜蜜素、甘草次酸等；矫味剂包括：甜味剂及各种香精；防腐剂包括：尼泊金类、苯甲酸、苯甲酸钠、山梨酸及其盐类、苯扎溴铵、醋酸氯乙定、桉叶油等；基质包括：PEG6000、PEG4000、虫蜡等。
本发明还提供上述白凤菜总黄酮提取物、上述制备方法制备得到的白凤菜总黄酮提取物、或者上述药物制剂在制备治疗非酒精性脂肪肝的药品或保健品中的应用。
本发明的技术方案具有如下优点：
(1)本发明提取分离得到一种含有80～85％的芦丁的白凤菜总黄酮提取物，药效实验结果表明，该提取物对非酒精性脂肪肝有较好的治疗作用，可显著改善非酒精性脂肪肝大鼠的血脂紊乱及脂肪变性，因此可以作为潜在的治疗非酒精性脂肪肝的药物；
(2)本发明白凤菜总黄酮提取物的制备方法，在提取步骤后，通过选择特定组成、特定配比的酶组成的复合酶在30-50℃下进行酶解，不仅避免了白凤菜总黄酮化合物的结构在高温下被破坏，而且使得白凤菜总黄酮化合物能够最大程度地被提取出来，进一步通过大孔树脂萃取浓缩和大孔树脂分离纯化步骤，使得白凤菜总黄酮化合物的提取率可达1.8％-2.0％，比现有方法中白凤菜总黄酮化合物的提取率提高可达30％以上，制备得到的白凤菜总黄酮提取物中芦丁的HPLC纯度可达80～85％。
附图说明
为了使本发明的内容更容易被清楚的理解，下面根据本发明的具体实施例并结合附图，对本发明作进一步详细的说明，其中：
图1是本发明实验例1中洗脱液的图谱；
图2是本发明实施例1制备的白凤菜总黄酮提取物的红外光谱图；
图3是本发明实施例1中芦丁对照品溶液的HPLC色谱图；
图4是本发明实施例1制备的白凤菜总黄酮提取物的HPLC色谱图；
图5是本发明实验例1中白凤菜总黄酮提取物对NAFLD大鼠肝脏组织病理学的影响(40×，HE染色)。
具体实施方式
本发明以下实施例和实验例中，白凤菜采自福建省漳州市龙文区登科村，经鉴定为白凤菜。
实施例1
本实施例白凤菜总黄酮提取物按照以下方法制备而成：
(1)提取：取白凤菜100g，加入30重量倍量的水进行提取，调节提取液的pH值为5，得反应液；
(2)酶解：然后向反应液中加入25g复合酶(该复合酶由重量比为1： 3：2的木瓜蛋白酶、纤维素酶和果胶酶组成)进行酶解，40℃强制循环反应 3小时，抽滤，收集滤液；
(3)萃取、浓缩：将滤液加入至盛有AB-8大孔树脂的提取罐中，在 30℃、100rpm下搅拌12小时，过滤，以AB-8大孔树脂的重量计，取吸附后的AB-8大孔树脂加入20重量倍量的体积浓度为75％的乙醇溶液，然后在 30℃、120rpm下搅拌12小时，过滤，即得萃取液，合并萃取液，将萃取液减压浓缩至白凤菜总黄酮的浓度为0.5mg/mL，得浓缩液；
(4)分离、纯化：将浓缩液10000rpm高速离心10分钟，取上清液加入装有大孔树脂D-101的层析柱内静止吸附60min，用体积浓度为75％的乙醇水溶液以5m/h的速度洗脱，在波长为510nm下测定吸光度，以吸光度值为纵坐标、以洗脱时间为横坐标作洗脱曲线图(其图谱如图1所示)，收集洗脱曲线中吸收峰范围内的洗脱液，浓缩、冷冻干燥，即得白凤菜总黄酮提取物。
经过计算，本实施例白凤菜总黄酮化合物的提取率为2.0％。
由图1可知，洗脱液在340min处出现一个明显的吸收峰，峰形较为单一，说明洗脱液中黄酮相对较纯。
A、本实施例白凤菜总黄酮提取物按照以下方法进行红外光谱鉴定：
取一定质量烘干后的芦丁标准品，以1：100加入烘干后的溴化钾，经研磨后制成固体压片，用傅立叶红外分光光度计在扫描范围4000-400cm-1、分辨率4、扫描次数为4的条件下绘制红外光谱图；同法绘制纯化后的白背天葵提取物的红外光谱图，对比鉴定。结果如图2所示。
由图2可知，芦丁标准品和白凤菜总黄酮提取物的红外光谱分别在 3685.455～3018.177cm-1左右均出现宽而强的吸收峰，是-OH的伸缩振动峰，表明存在酚羟基或糖上的羟基，且数目较大；在2914.036cm-1处出现弱吸收峰，是碳氢键的伸缩振动峰，说明饱和碳上的氢较少；在1654.694cm-1处出现C＝O的伸缩振动中强峰，两者位置和峰型基本一致，说明提取物是黄酮类物质；在1371.88、1362.89cm-1处出现羟基的弯曲振动峰；在804.80、810.56cm-1处出现苯环邻位氢引起的吸收峰；在1010.07～696.62cm-1处出现苯环上取代基位置引起的吸收峰，但峰位置不同，说明提取物与芦丁的羟基取代位置不同；这些表明，提取物中含有羟基、羰基以及不同位置取代的苯环等官能团，特征吸收峰基本一致。因此可确定提取物是黄酮类化合物。
B、按照以下方法通过液相色谱分析本实施例白凤菜总黄酮提取物中的芦丁的含量:
B1、液相色谱条件的确定
液相色谱条件:保护柱:Eclipse XDB-C18 AnalyticalGuard Column (4.6×12.5mm，5μm)：ZOR BZX Eclipse XDB-C18(4.6×150mm，5μm)；流速：0.5mL/min；柱温：35℃；检测波长：368nm、254nm、210nm；进样体积：10μL；流动相:0.03％甲酸水溶液(A)，乙腈(B)；梯度洗脱程序如下：0～10min，20％B；10～12min，20％～24％B；12～20min，24％B； 20～25min，24％～30％B；25～48min，30％B。
B2、对照品溶液的配置
准确称取芦丁0.001g，溶解于1mL甲醇中，制成1mg/mL的单一对照品溶液。并用一次性滤膜过滤，装入小试管中待用。
B3、测定
精密吸取对照品溶液、供试品溶液(实施例1制备的白凤菜黄酮提取物，配制成浓度为1μg/μL的甲醇溶液)，按照液相色谱检测条件分别进行检测分析。
对照品溶液的HPLC色谱图如图3所示，供试品溶液的HPLC色谱图如图4所示。
由图3可知，芦丁对照品溶液可在10分钟内完全分离，芦丁在本实验的色谱条件下，色谱基线基本平直，呈现色谱峰无拖尾现象，杂质也无干扰，且出峰较早，其保留时间为2.745min。
由图4，通过面积归一法计算可知，白凤菜提取物中芦丁的含量为 81.29％。
实施例2
本实施例白凤菜总黄酮提取物按照以下方法制备而成：
(1)提取：取白凤菜100g，加入20重量倍量的水进行提取，用稀氢氧化钠溶液调节提取液的pH值为8，得反应液；
(2)酶解：然后向反应液中加入20g复合酶(该复合酶由重量比为0.5： 5：1的木瓜蛋白酶、纤维素酶和果胶酶组成)进行酶解，30℃强制循环反应 4小时，抽滤，收集滤液；
(3)萃取、浓缩：将滤液加入至盛有DM-130大孔树脂的提取罐中，在 30℃、80rpm下搅拌24小时，过滤，以DM-130大孔树脂的重量计，取吸附后的DM-130大孔树脂加入10重量倍量的体积浓度为95％的乙醇溶液，然后在30℃、80rpm下搅拌24小时，过滤，即得萃取液，合并萃取液，将萃取液减压浓缩至白凤菜总黄酮的浓度为0.5mg/mL，得浓缩液；
(4)分离、纯化：将浓缩液6000rpm高速离心8分钟，取上清液加入装有大孔树脂HP-21的层析柱内静止吸附60min，用体积浓度为80％的乙醇水溶液以3m/h的速度洗脱，在波长为510nm下测定吸光度，以吸光度值为纵坐标、以洗脱时间为横坐标作洗脱曲线图，收集洗脱曲线中吸收峰范围内的洗脱液，浓缩、冷冻干燥，即得白凤菜总黄酮提取物。
经过计算，本实施例白凤菜总黄酮化合物的提取率为1.82％。
按照实施例1中“B项下”测定本实施例白凤菜总黄酮提取物中的芦丁。通过测定分析可知，HPLC图谱中，本实施例白凤菜总黄酮提取物中的芦丁含量为80％。
实施例3
本实施例白凤菜总黄酮提取物按照以下方法制备而成：
(1)提取：取白凤菜100g，加入60重量倍量的水进行提取，用稀盐酸调节提取液的pH值为4，得反应液；
(2)酶解：然后向反应液中加入32g复合酶(该复合酶由重量比为1.5： 2：3的木瓜蛋白酶、纤维素酶和果胶酶组成)进行酶解，50℃强制循环反应 1小时，抽滤，收集滤液；
(3)萃取、浓缩：将滤液加入至盛有ZH-01大孔树脂的提取罐中，在 30℃、150rpm下搅拌6小时，过滤，以ZH-01大孔树脂的重量计，取吸附后的ZH-01大孔树脂加入30重量倍量的体积浓度为70％的乙醇溶液，然后在 30℃、150rpm下搅拌6小时，过滤，即得萃取液，合并萃取液，将萃取液减压浓缩至白凤菜总黄酮的浓度为0.5mg/mL，得浓缩液；
(4)分离、纯化：将浓缩液8000rpm高速离心5分钟，取上清液加入装有大孔树脂XAD-3的层析柱内静止吸附60min，用体积浓度为70％的乙醇水溶液以15m/h的速度洗脱，在波长为510nm下测定吸光度，以吸光度值为纵坐标、以洗脱时间为横坐标作洗脱曲线图，收集洗脱曲线中吸收峰范围内的洗脱液，浓缩、冷冻干燥，即得白凤菜总黄酮提取物。
经过计算，本实施例白凤菜总黄酮化合物的提取率为1.91％。
按照实施例1中“B项下”测定本实施例白凤菜总黄酮提取物中的芦丁。通过测定分析可知，HPLC图谱中，本实施例白凤菜总黄酮提取物中的芦丁含量为85％。
实验例1白凤菜总黄酮提取物对非酒精性脂肪肝大鼠的治疗作用研究
1、实验目的
研究白凤菜总黄酮提取物对高脂饲料诱导的非酒精性脂肪肝(NAFLD) 模型大鼠的治疗效果。
2、材料与方法
2.1 实验动物
健康SPF级雄性Spague-Dawlay(SD)大鼠62只，体重210±10g，由上海市西普尔-必凯实验动物有限公司提供(合格证号：2007000531494，许可证号：SCXK(沪)2007-0005)。
2.2 供试药物与实验试剂
以实施例1制备的白凤菜总黄酮提取物作为供试药物，高、中、低各组临用前，用蒸馏水稀释后给药，其中三个剂量分别为：低剂量6mg/10mL，中剂量12mg/10mL，高剂量24mg/10mL。
总甘油三酯(TG)、总胆固醇(TC)、丙氨酸氨基转移酶(ALT)、天门冬氨酸转移酶(AST)高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL- C)试剂盒购于南京建成工程研究所；高脂饲料(猪油10％、胆固醇2％、猪胆盐0.7％、基础饲料、87.3％)由福州闽侯竹岐动物服务中心提供；普通饲料由福建中医药大学实验动物中心提供。
2.3 实验仪器
电子天平(上海奥豪斯仪器有限公)，BX51T-PHD-J11显微镜(日本 OLYMPUS公司)，低速离心机(美国Thermo公司)，生物组织石蜡包埋机 (湖北孝感亚光医用电子技术有限公司)，生物组织自动脱水机(亚光医用电子技术有限公司)，全自动石蜡切片机(德国徕卡仪器有限公司)，BS- 120全自动生化分析仪(深圳迈瑞生物医疗电子股份有限公司)。
3、实验方法
3.1 动物分组及模型建立
选择SPF级SD雄性大鼠62只，适应性喂养一周后，按体重随机分成2 组，分别为正常对照组(16只)和高脂组(46只)。正常对照组给予基础饲料饲养，高脂组以高脂饲料喂养，动物自由进食、饮水，明暗交替各12h，每周称量体重一次。
实验6周后分别从正常对照组和高脂饮食组随机抽取6只处死，取肝脏做组织病理切片；肝脏组织病理学观察，结果表明，模型组大鼠肝脏脂肪变严重，单位面积脂变已超过2/3，肝组织呈弥漫性大泡性重度脂肪变性，肝细胞点状坏死及肝组织轻度纤维化增生，这表明非酒精性脂肪肝模型建立成功。
确定模型成功后，高脂组剩余40只大鼠随机分为模型对照组、白凤菜总黄酮提取物低剂量组、白凤菜总黄酮提取物中剂量组和白凤菜总黄酮提取物高剂量组，每组10只。从第7周开始，除空白对照组和模型组灌服生理盐水外的其余各组大鼠给予不同剂量的白凤菜总黄酮提取物，(低剂量组给予 6mg/10mL白凤菜总黄酮提取物，中剂量组给予12mg/10mL白凤菜总黄酮提取物，高剂量组给予24mg/10mL白凤菜总黄酮提取物。于第10周末隔夜禁食12h，次日经戊巴比妥钠40mg/kg腹腔内麻醉后，腹主动脉法取血，于 3000r/min，离心l5min，分离血清，-80℃冰箱保存待检。
3.2 实验数据观察与检测
实验过程中，观察大鼠活动度、毛发光泽，食欲及死亡等情况，每周称量体重并记录。摘取肝脏和内脏脂肪垫，称重拍照观察各组大鼠肝脏大体形态后，取肝右叶部分用4％多聚甲醛溶液固定，常规石蜡包埋，用于病理切片，常规HE染色，光镜观察并参照中华肝脏病学会脂肪肝及酒精性肝病学组制定的NAFLD诊断标准评价组织脂肪变性、炎症和坏死程度。全自动生化分析仪测定血清丙氨酸氨基转移酶(ALT)、天门冬酸氨基转移酶 (ASL)、胆固醇(TC)、甘油三脂(TG)、高密度脂蛋白(HDL-C)和低密度脂蛋白(LDL-C)的含量。
4、实验数据处理
所有实验数据均使用SPSS18.0软件包进行分析，结果用均数±标准差表示，多组数据之间比较使用单因素方差分析，两组数据之间比较采用t检验；计数资料用秩和检验。P<0.05表示有显著性差异。
5、实验结果
5.1 白凤菜总黄酮提取物对NAFLD大鼠肝脏大体形态的影响
正常对照组大鼠肝脏外观呈鲜红色，大小正常，形状规则，质地柔软，表面光滑；模型组大鼠肝脏体积明显增大，呈奶黄色，边缘钝而厚，表面有弥漫性细颗粒样隆起，切面油腻，质地较脆，局部有黄白色变性灶；白凤菜总黄酮提取物各剂量组肝脏体积较正常略增大，颜色较模型组偏红，接近正常色,切面无明显油腻。
5.2 白凤菜总黄酮提取物对NAFLD大鼠肝脏组织病理学的影响
白凤菜总黄酮提取物对NAFLD大鼠肝脏组织病理学的影响如图5所示。
由图5可知，正常对照组大鼠肝小叶结构完整、细胞轮廓清晰，中央静脉大而壁薄，肝索呈放射状排列，无肝细胞脂肪变性及炎症细胞浸润；模型组肝组织胞浆内可见广泛弥漫分布的大脂肪空泡，肝细胞体积增大，肝索排列紊乱，肝窦狭窄，细胞核被挤向一边，病变以中央静脉周围最为明显，有炎性细胞浸润，累及肝小叶，主要为大泡性脂肪变性；白凤菜总黄酮提取物各剂量组大鼠肝细胞脂肪变性数量及程度较模型组明显减轻，仅高倍镜下可见肝细胞有小空泡样变。
5.3 白凤菜总黄酮提取物对NAFLD大鼠肝重、内脏脂肪垫的影响
白凤菜总黄酮提取物对NAFLD大鼠肝重、内脏脂肪垫的影响如表1所示。
表1 白凤菜总黄酮提取物对NAFLD大鼠肝重、内脏脂肪垫的影响(n＝10，)
注：与对照组比较，#P＜0.05，##P＜0.01；与模型组比较，*P＜0.05
由表1可知，模型组大鼠肝重较正常对照组明显升高，差异有统计学意义(P<0.01)；白凤菜总黄酮提取物各剂量组与模型组差异均有统计学意义 (P<0.05)；模型组大鼠内脏脂肪垫(肾周和附睾)较正常对照组重量明显升高，白凤菜各剂量组均能明显减轻肝重，减轻内脏脂肪垫重量，差异有统计学意义(P<0.05)，但在内脏脂肪垫重量方面各实验组之间差异无统计学意义(P>0.05)。
5.4白凤菜总黄酮提取物对NAFLD大鼠血清生化指标的影响
白凤菜总黄酮提取物对NAFLD大鼠血清生化指标的影响如表2-4所示。
表2 白凤菜总黄酮提取物对NAFLD大鼠血清TG、TC的影响(n＝10，)
注：与对照组比较，#P＜0.01；与模型组比较，*P＜0.05
表3 白凤菜总黄酮提取物对NAFLD大鼠血清ALT、AST的影响(n＝10，)
注：与对照组比较，#P＜0.05；与模型组比较，*P＜0.05
表4白凤菜总黄酮提取物对NAFLD大鼠HDL-C、LDL-C含量的影响(n＝10，)
注：与对照组比较，#P＜0.05；与模型组比较，*P＜0.05
由表2-3可知，模型组大鼠血清TG、TC、ALT及AST含量显著高于对照组(P<0.05)；白凤菜总黄酮提取物各剂量组大鼠血清TG、TC、ALT、 AST含量均显著低于模型组(P<0.05)。
由表4可知，与对照组相比，模型组大鼠的LDL-C显著上升，而HDL- C下降明显，均具有统计意义(P<0.05)；白凤菜总黄酮提取物各剂量组的 HDL-C与模型组比较无明显统计学差异，白凤菜总黄酮提取物高、中剂量组的LDL-C与模型组比较显著降低(P<0.05)。
6、实验结论
白凤菜总黄酮提取物对非酒精性脂肪肝有较好的治疗作用，可显著改善非酒精性脂肪肝大鼠的血脂紊乱及脂肪变性。
显然，上述实施例仅仅是为清楚地说明所作的举例，而并非对实施方式的限定。对于所属领域的普通技术人员来说，在上述说明的基础上还可以做出其它不同形式的变化或变动。这里无需也无法对所有的实施方式予以穷举。而由此所引伸出的显而易见的变化或变动仍处于本发明创造的保护范围之中。
Claims (10)
1.一种白凤菜总黄酮提取物，其特征在于，以重量百分含量计，含有80～85％的芦丁。
2.一种权利要求1所述的白凤菜总黄酮提取物的制备方法，其特征在于，包括以下步骤：
(1)提取：取白凤菜加入提取溶剂进行提取，调节提取液的pH值为4-8，得反应液；
(2)酶解：然后向反应液中加入复合酶进行酶解，30-50℃强制循环反应1-4小时，抽滤，收集滤液；
(3)萃取、浓缩：将滤液用大孔树脂A进行萃取，合并萃取液，将萃取液浓缩，得浓缩液；
(4)分离、纯化：将浓缩液离心，取上清液用大孔树脂B分离纯化，在波长为510nm下测定吸光度，收集洗脱液，浓缩、干燥，即得。
3.根据权利要求2所述的白凤菜总黄酮提取物的制备方法，其特征在于，
所述酶解步骤中，采用由木瓜蛋白酶、纤维素酶和果胶酶组成的复合酶进行酶解；
所述复合酶与所述白凤菜的重量之比为：1:5～1:3。
4.根据权利要求2或3所述的白凤菜总黄酮提取物的制备方法，其特征在于，所述复合酶中，木瓜蛋白酶、纤维素酶和果胶酶三者的重量比为(0.5-1.5)：(2-5)：(1-3)。
5.根据权利要求4所述的白凤菜总黄酮提取物的制备方法，其特征在于，所述复合酶中，木瓜蛋白酶、纤维素酶和果胶酶三者的重量比为1：3：2。
6.根据权利要求2-5任一项所述的白凤菜总黄酮提取物的制备方法，其特征在于，
所述大孔树脂A选自AB-8、DM-130、HZ841、ZH-00、ZH-01、ZH-02、ZH-03、CAD-40、CAD-45、BS-30中的至少一种；
所述大孔树脂B选自D-101、D-140、D-141、XAD-3、XAD-4、HP-20、HP-21、LD-605、LSA-10中的至少一种。
7.根据权利要求2-6任一项所述的白凤菜总黄酮提取物的制备方法，其特征在于，
所述提取步骤中，提取溶剂为水，所述白凤菜与所述水的重量之比为1：(20-60)。
8.根据权利要求2-7任一项所述的白凤菜总黄酮提取物的制备方法，其特征在于，
所述分离、纯化步骤中，洗脱溶剂为体积浓度为70-80％的乙醇水溶液，洗脱速度为3-15m/h；
所述浓缩液中，白凤菜总黄酮的浓度为0.5mg/mL。
9.一种药物制剂，其特征在于，以权利要求1所述的白凤菜总黄酮提取物、或者权利要求2-8任一项所述的制备方法制备得到的白凤菜总黄酮提取物为活性成分，按照常规工艺，加入常规辅料制成临床上可接受的片剂、胶囊剂、散剂、合剂、丸剂、颗粒剂、糖浆剂、贴膏剂、栓剂、气雾剂、软膏剂或注射剂。
10.权利要求1所述的白凤菜总黄酮提取物、权利要求2-8任一项所述的制备方法制备得到的白凤菜总黄酮提取物、或者权利要求9所述的药物制剂在制备治疗非酒精性脂肪肝的药品或保健品中的应用。
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