CN113116871A - 芪类stilbene化合物在抗衰老小分子药物中的应用 - Google Patents
芪类stilbene化合物在抗衰老小分子药物中的应用 Download PDFInfo
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Abstract
本发明公开了芪类stilbene化合物在延长线虫寿命的药物中的应用。本发明所述的线虫为秀丽隐杆线虫。所述的线虫食物为尿嘧啶缺陷型大肠杆菌(E.coli)OP50。线虫的给药方式：是在配置OP50培养倒板之前加入，并使得药物在OP50培养基中的终浓度为范围为40～120μM；摇混均匀后，倒入35mm的无菌培养皿。本发明通过体内实验鉴定了，芪类(stilbene)化合物抗衰老延长寿命功能，提供了芪类化合物抗衰老方面潜在应用理论依据。
Description
技术领域
本发明涉及芪类stilbene化合物新应用技术领域，具体涉及在延长线虫寿命中的应用，属于抗衰老小分子药物新发现应用。
背景技术
根据第六次全国人口普查结果显示，中国65岁以上人口已经占全国的8.87％，已进入人口老龄化社会。随着社会人口的老龄化日趋加重，老年性疾病如糖尿病、冠心病等明显增加(满都拉等，2017)，而衰老是导致这些疾病增加的重要因素。衰老又称细胞的程序性死亡，广义上指，衰老的发生是因为随着年龄的增加，细胞的自我修复功能减退，导致人体抵抗力下降，引起疾病发生率增高。目前对衰老的发生机制还没有具体分子机制说明，2013年Carlos等人提出了衰老的九大特征：(1)基因组不稳定(Genomic instability)；(2)端粒的缩短(Telomere attrition)；(3)表观遗传学的改变(Epigenetic alterations)；(4)蛋白质动稳态失衡(Loss of proteostasis)；(5)营养感知失调(Deregμlated nutrient-sensing)；(6)线粒体功能障碍(Mitochondrial dysfunction)；(7)细胞衰老(Cellμlarsenescence)；(8)干细胞耗竭(Stem cell exhaustion)；(9)细胞间通讯改变(Alteredintercellμlar communication)。这些九大衰老特征并不都是有害的，如严重的线粒体DNA突变、端粒丢失会损伤机体；而轻微的线粒体功能障碍对机体的抵抗时有益的，由此可见，损伤程度不同所造成的损害也不同，衰老的发生也不是单一因素导致的，而是由多个复杂的因素共同作用而成。根据研究者提出衰老的九大特点，人们针对衰老提出了几大干预措施，其中包括抗炎症药物、清除衰老的干细胞、激活分子伴侣、饮食限制及衰老相关通路的激活等。这意味着衰老可以受到人为调控。
芪类stilbene化合物是指具有均二苯乙烯母核或其聚合物的一类物质的总称。这类物质在植物界的正常组织中含量较低，单和二酚羟基芪类化合物主要存在于植物组织木质部的薄壁细胞中。芪类化合物具有广泛的生物活性，除早已知道的抗菌作用外，近年来又发现一些芪类有降血脂的作用，从河套大黄中分出的土大黄苷(rhaponticin)已应用于临床治疗高血脂症。
白皮杉醇(Piceatannol)是一种天然的二苯乙烯，它的化学式为C14H12O4，如图5所示(Sangjin Hong等)，中文别名：3'-羟基白藜芦醇；比杉特醇；4-[2-(3,5-二羟基苯基)乙烯基]-1,2-苯二酚；(E)-3,3',4,5'-二苯乙烯四醇。纯的白皮杉醇一般是白色结晶，也有无定形粉末，对光敏感，容易氧化变色。白皮杉醇是一种化学结构类似于白藜芦醇的化合物，广泛存在于葡萄、蓝莓、百香果等蔬果中，其主要功能与白藜芦醇基本一致，但是由于比白藜芦醇多一个羟基，同等质量的白皮杉醇的抗氧化和清除自由基的效果是白藜芦醇的4-5倍。白皮杉醇是多酚类化合物，具有许多有益的作用，例如抗氧化、抗炎、抗动脉粥样硬化等，有良好的开发前景。
因此，开展白皮杉醇功能鉴定研究十分必要。目前对白皮杉醇的功能鉴定研究仅在抗氧化以及改善机体功能方面有部分报道。如尹开云等在《大黄类药材中白皮杉醇的提取方法、微胶囊分子包埋方法及其在化妆品中的应用》一文中通过优化大黄类药材中白皮杉醇的提取方法提高了白皮杉醇对于皮肤的抗氧化性。如翁丹等在《白皮杉醇在制备防治糖尿病药物中的应用》一文中发现白皮杉醇对糖尿病具有良好的治疗效果，尤其是对于1型糖尿病具有良好的治疗效果。这些研究均认为白皮杉醇具有改善机体健康功能方面的作用，而关于白皮杉醇寿命影响方面的研究未见报道。因此，开展白皮杉醇的寿命影响鉴定和应用研究具有十分重要的现实意义。
发明内容
针对以上衰老调控相关的小分子化合物，本发明提供了芪类stilbene化合物芪类stilbene化合物在抗衰老小分子药物中的应用。在延长线虫寿命的药物中的应用，并提供了白皮杉醇(piceatannol)延长寿命的最适浓度范围。
为了达到上述发明目的，本发明所采用的技术方案如下：本发明的芪类stilbene化合物在抗衰老小分子药物中的应用。芪类stilbene化合物在延长线虫寿命的药物中的应用。
进一步地，所述的线虫为秀丽隐杆线虫。
进一步地，所述的线虫食物为尿嘧啶缺陷型大肠杆菌(E.coli)OP50。
更进一步地，线虫的给药方式：是在配置OP50培养倒板之前加入，并使得药物在OP50培养基中的终浓度为范围为40～120μM；摇混均匀后，倒入35mm的无菌培养皿。
进一步地，制备OP50培养基：溶菌肉汤固体培养基Lysogeny Broth,LB是OP50生存的主要食物来源，配制1000ml LB固体培养基：称取下列试剂于1L锥形瓶中：胰蛋白10g、NaCl 10g、酵母提取物5g、琼脂15g(OP50液体培养基不需要加)，用去离子水定容到1L，高压灭菌后，制得OP50培养基；
同步化线虫：将发育至day 1的可产卵线虫置于培养基中培养过夜，10h后去除母虫得到同一时期的线虫，20℃培养箱培养至线虫发育到young adult时期进行转移。
进一步地，环境条件设置：线虫同步化后，在线虫培养基中培养至成虫，各组曝光处理后，20℃恒温避光培养箱培养。
进一步地，线虫寿命实验分为以下五组：第一组：未对线虫进行任何处理；第二组：对线虫给予40uM白皮杉醇处理；第三组：对线虫给予50uM白皮杉醇处理；第四组：对线虫给予100uM白皮杉醇处理；第五组：对线虫给予120uM白皮杉醇处理。
有益效果：本发明步骤简单，效果好，本发明通过体内实验鉴定了，芪类(stilbene)化合物抗衰老延长线虫寿命功能，提供了芪类化合物延长哺乳类动物寿命的潜在应用理论依据。通过体内实验鉴定了白皮杉醇(piceatannol)在线虫中延长寿命的最适宜浓度范围，提供了白皮杉醇(piceatannol)在延长线虫寿命中的应用。
附图说明
图1为本发明的给予秀丽隐杆线虫40uM白皮杉醇的寿命实验图。
图2为本发明的给予秀丽隐杆线虫50uM白皮杉醇的寿命实验图。
图3为本发明的给予秀丽隐杆线虫100uM白皮杉醇的寿命实验图。
图4为本发明的给予秀丽隐杆线虫120uM白皮杉醇的寿命实验图。
图5为本发明的不同浓度的白皮杉醇对秀丽隐杆线虫寿命的影响图。
图6为本发明的最简单的白皮杉醇小分子化合物结构体。
具体实施方式
为了便于理解本发明，下面将参照相关附图对本发明进行更加全面的描述，附图中给出了本发明的若干实施例，但是本发明可以通过不同的形式来实现，并不限于文本所描述的实施例，相反的，提供这些实施例是为了使对本发明公开的内容更加透彻全面。
实施例1
实验原料
试剂：氯化钠、磷酸氢二钾、磷酸二氢钾、磷酸氢二钠、硫酸镁、胆固醇、琼脂粉、胰蛋白胨、酵母粉、蛋白胨、一水合柠檬酸、一水合柠檬酸三钾、乙二胺四乙酸(EthyleneDiamine Tetraacetic Acid,EDTA)、柠檬酸钾、七水合硫酸亚铁、四水合氯化锰、七水合硫酸锌、五水合硫酸铜、5-氟脱氧尿苷(Floxuridine,FUDR)(Sigma)、Pyropheophorbide-a(Frontier Scientific)。
实验菌株和虫株：尿嘧啶缺陷型大肠杆菌(E.coli)OP50；野生型N2菌株。
实验仪器：
AL104-IC—电子天平(梅特勒-托利多仪器公司)、SMZ-168—解剖显微镜(Motic公司)、DK-420—电热恒温水槽(上海森信实验仪器有(哈尔滨东联公司)、ZXSD-81430—生化培养(上海智诚分析仪器有限公司)、D-1—自动蒸气灭菌器(北京发恩科贸有限公司)。
本发明芪类stilbene化合物在延长线虫寿命的药物中的应用。
所述的线虫为秀丽隐杆线虫。
所述的线虫食物为尿嘧啶缺陷型大肠杆菌(E.coli)OP50。
线虫培养方法：
在超净台无菌环境中，将新鲜配制的含有OP50的NGM培养基取出，置于超净台冷却5分钟。通过解剖显微镜，挑取数只L1或L2时期的线虫至NGM培养基中，再将培养基置于20℃培养箱中培养。
不同浓度白皮杉醇对线虫寿命的影响实验步骤：
1.OP50培养基准备：
在OP50培养基分装于培养皿之前加入白皮杉醇,使之终浓度分别是40μM、50μM、100μM、120μM。
制备OP50培养基：溶菌肉汤固体培养基Lysogeny Broth,LB是OP50生存的主要食物来源，配制1000ml LB固体培养基：称取下列试剂于1L锥形瓶中：胰蛋白10g、NaCl 10g、酵母提取物5g、琼脂15g(OP50液体培养基不需要加)，用去离子水定容到1L，高压灭菌后，制得OP50培养基；
2.同步化线虫：将发育至day 1的可产卵线虫置于培养基中培养过夜，10h后去除母虫得到同一时期的线虫，20℃培养箱培养至线虫发育到young adult时期进行转移。
不同浓度白皮杉醇线虫培养基配制：
NGM(Nematode Growth Media,NGM)培养基配制：称取下列试剂于1L锥形瓶中：蛋白胨2.5g、NaCl 3g、琼脂20g，去离子水定容到1L。高压灭菌后分别加入1M的CaCl2和1M的MgSO4各1ml、5mg/ml胆固醇1ml和磷酸盐缓冲液(KPI)25ml。混匀后分别加入白皮杉醇,使之终浓度分别是40μM、50μM、100μM、120μM并分装至培养皿中。室温冷却后加入新鲜的OP50，37℃培养箱过夜培养后置于4℃冰箱备用。
环境条件设置：线虫同步化后，在线虫培养基中培养至成虫，20℃恒温避光培养箱培养。
线虫的给药方式：是在配置NGM培养基时加入，摇混均匀后，倒入35mm的无菌培养皿。
3.线虫寿命实验：
将同步化得到的线虫转移到上述加了FUDR和白皮杉醇的培养基中，确保每个培养基转移30条线虫。
培养至成虫，每隔2-3天将线虫转移到相应加了FUDR和白皮杉醇的新皿中防止培养基污染。对于钻到培养基底部、爬在皿壁上失水致死、无顾丢失等情况不计入死亡数据，但将其记为实验对象并进行统计分析。寿命实验分析用在线应用(OASIS；sbi.postech.ac.kr/oasis)进行统计分析，上述实验独立重复三次。
以上显示和描述了本发明的基本原理、主要特征和本发明的优点。本行业的技术人员应该了解，本发明不受上述实施例的限制，上述实施例和说明书中描述的只是说明本发明的原理，在不脱离本发明精神和范围的前提下，本发明还会有各种变化和改进，本发明要求保护范围由所附的权利要求书、说明书及其等效物界定。
Claims (8)
1.芪类stilbene化合物在延长线虫寿命的药物中的应用。
2.根据权利要求1所述的应用，其特征在于：所述的线虫为秀丽隐杆线虫。
3.根据权利要求1所述的应用，其特征在于：所述的线虫食物为尿嘧啶缺陷型大肠杆菌(E.coli)OP50。
4.根据权利要求1所述的应用，其特征在于：线虫的给药方式：是在配置OP50培养倒板之前加入，并使得药物在OP50培养基中的终浓度为范围为40～120μM；摇混均匀后，倒入35mm的无菌培养皿。
5.根据权利要求4所述的应用，其特征在于：制备OP50培养基：溶菌肉汤固体培养基Lysogeny Broth,LB是OP50生存的主要食物来源，配制1000ml LB固体培养基：称取下列试剂于1L锥形瓶中：胰蛋白10g、NaCl 10g、酵母提取物5g、琼脂15g，用去离子水定容到1L，高压灭菌后，制得OP50培养基；
同步化线虫：将发育至day 1的可产卵线虫置于培养基中培养过夜，10h后去除母虫得到同一时期的线虫，20℃培养箱培养至线虫发育到young adult时期进行转移。
6.根据权利要求5所述的应用，其特征在于：环境条件设置：线虫同步化后，在线虫培养基中培养至成虫，20℃恒温避光培养箱培养。
7.根据权利要求6所述的应用，其特征在于：线虫寿命实验分为以下五组：第一组：未对线虫进行任何处理；第二组：对线虫给予40uM白皮杉醇处理；第三组：对线虫给予50uM白皮杉醇处理；第四组：对线虫给予100uM白皮杉醇处理；第五组：对线虫给予120uM白皮杉醇处理。
8.根据权利要求1至7任一项所述的应用，其特征在于：所述的芪类stilbene化合物为白皮杉醇piceatannol。
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| CN115039738A (zh) * | 2022-04-07 | 2022-09-13 | 南京大学 | 一种光子晶体薄膜在减缓线虫光毒害中的应用 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060025337A1 (en) * | 2003-07-01 | 2006-02-02 | President And Fellows Of Harvard College | Sirtuin related therapeutics and diagnostics for neurodegenerative diseases |
-
2021
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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Non-Patent Citations (1)
| Title |
|---|
| PEIYI SHEN,ET AL.: "Piceatannol extends the lifespan of Caenorhabditis elegans via DAF-16", 《BIOFACTORS》 * |
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|---|---|---|---|---|
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| CN115039738A (zh) * | 2022-04-07 | 2022-09-13 | 南京大学 | 一种光子晶体薄膜在减缓线虫光毒害中的应用 |
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Application publication date: 20210716 |