CN105213209A - 天麻素作为酪氨酸酶抑制剂的应用 - Google Patents
天麻素作为酪氨酸酶抑制剂的应用 Download PDFInfo
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- CN105213209A CN105213209A CN201510701308.3A CN201510701308A CN105213209A CN 105213209 A CN105213209 A CN 105213209A CN 201510701308 A CN201510701308 A CN 201510701308A CN 105213209 A CN105213209 A CN 105213209A
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Abstract
本发明公开了天麻素具有强烈的酪氨酸酶抑制作用，能显著降低细胞黑色素生成量，其效果明显优于目前在化妆品中常用的作为酪氨酸酶抑制剂的熊果苷，并且具有较好的稳定性和较低的细胞毒性，可应用于防治老年斑、色斑等皮肤色素沉着和美白，以及作为食品保鲜添加剂。
Description
技术领域
本发明属于生物和医药技术领域，涉及天麻素的新应用，具体涉及天麻素作为酪氨酸酶抑制剂在药物、化妆品和食品添加剂中的应用。
背景技术
随着人们生活水平和审美标准的不断提高，对拥有健康美白肌肤的愿望日益迫切。在中国、日本、韩国和印度这样的国家，皮肤增白具有广阔的市场，这些地区的众多女性把更白的皮肤视为美丽、健康和崇高社会地位的象征。一项研究估计，亚洲国家一半的女性使用皮肤增白霜，每年的花费相当于数十亿美元。人们也使用这类产品褪去难看的老年斑、雀斑和收集了色素的疤痕。因此，有关皮肤美白类化妆品已成为护肤类化妆品的主流产品，其消费市场日益扩大。然而，有些增白化妆品中含有有毒的化学物质，如具有较强的细胞毒性的汞、对二苯酚和氢醌化合物等，长期使用能导致发红、痒，甚至出现炎症等皮肤问题。更为严重的是，这些化学合成物质如果频繁地高剂量使用，一些增白成分可能增加皮肤癌的风险，许多国家已经禁止使用。因此，需要研究更安全、更有效的替代品。
研究表明，皮肤色素沉着是由于黑色素细胞内黑色素产生过多导致的，而酪氨酸酶是黑色素合成过程中的关键酶，其广泛分布于微生物、动植物和人体中。黑色素合成量的多少与酪氨酸酶酶量的表达和活性大小密切相关，减少酪氨酸酶的产生和抑制其活性即可控制黑素生成量。因此，通过降低酪氨酸酶表达量和抑制其活性，可以有效地限制皮肤中黑色素合成，从而减少皮肤的色素沉着，达到治疗各种色斑或者与之相关的各种皮肤病的目的。所以，酪氨酸酶抑制剂在化妆品、临床药物、防止水产品等食品褐变应用研究越来越受到重视。
许多天然植物提取物中含有抑制酪氨酸酶的活性物质，由于其作用安全而且温和，能有效地清除氧自由基，而被广泛作为皮肤美白护理的原料用于开发成美白化妆品，例如曲酸和熊果苷等。但是仍然存在问题，不能满足消费市场需求。曲酸由于性质不稳定，美白效果较弱；熊果苷虽然相对较为稳定，但使用浓度过高，在有增白效果的浓度时具有毒性。有些植物提取物往往由于颜色较深，对化妆品外观产生不良影响。因此，从植物中寻找安全有效和颜色较淡的美白天然化合物已成为化妆品行业研究发展趋势。
此外，果品蔬菜、鱼虾类水产品的保鲜也是亟待解决的问题。如鱼虾水产品和香蕉、土豆等蔬菜水果在加工和储存过程中往往会变黑。这是由于其内源酚氧化酶和酪氨酸酶容易发生褐变反应，形成黑褐色斑块，从外观上就降低了品质，带来巨大经济损失。因此，寻找一种防止食品褐变的安全有效的天然化合物作为添加剂，即通过寻找对酪氨酸酶具有特效的抑制剂用于果品蔬菜和水产品保鲜无疑是一种有效的方法。
发明内容
熊果苷又名熊果素，呈白色针状结晶或粉末。萃取自熊果的叶子，能够加速黑色素的分解与排泄，从而减少皮肤黑色素沉积，祛除色斑和雀斑，同时还有杀菌、消炎的作用，主要用于高级化妆品的制备，起到美白的效果。
熊果苷的结构如式(I)所示：
天麻(GastrodiaelataBl.)是一种传统的中药材，其主要生物活性物质是天麻素，天麻素化学名称：4-羟甲基苯-β-D-吡喃葡萄糖苷【4-(hydroxymethyl)phenyl-β-D-Glucopyranoside】，化学分子式：C13H18O7，其化学结构式如式(II)所示：
临床试验已证实天麻素具有较好的镇静和安眠作用，可作为治疗痛眩晕、肢体麻木、惊痛抽搐、头痛和癫痫辅助治疗药物。近几年研究发现天麻素还能够有效的治疗血管性痴呆。
天麻素化学结构与熊果苷类似，熊果苷是在葡萄糖上连接一个酚羟基基团，天麻素是在葡萄糖上连接一个苯甲醇基团，天麻素比熊果苷具有更好的稳定性。鉴于此，发明人有理由相信天麻素也应具有类似熊果苷的抑制酪氨酸酶，减少细胞中黑色素的生成量的效果，更稳定的结构甚至带来更佳的抑制效果。
通过天麻素对酪氨酸酶抑制活性的测定和抑制时间分析，发现天麻素表现出对酪氨酸酶具有抑制活性，并呈现浓度依赖性；以熊果苷作为对照，发现天麻素对酪氨酸酶抑制作用明显；通过抑制时间分析发现，天麻素的抑制作用具有较好的稳定性。
通过天麻素对人黑色素瘤细胞的黑色素生成量和细胞毒性试验发现，以熊果苷作为对照，天麻素能显著减少细胞黑色素生成量并具有较低的细胞毒性，说明天麻素能够有效调控黑色素生成途径而且安全性较好。
本发明证实了天麻素对酪氨酸酶活性具有有效地抑制作用，能显著减少细胞中黑色素的生成量。
作为美白化妆品成分，天麻素可以单独使用，也可以与其它化合物混合使用，并与药学上所允许的辅料或常规的药用载体一起用作抑制黑色素生成的美白化妆品。本发明还可以任意选择添加如下1种或者2种以上美白成分：如内皮素拮抗剂、桑树提取物、甘草提取物、胎盘提取液、果酸、芦荟、L-抗坏血酸，也可以采用不排除上述罗列的其它美白剂成分。
天麻素可进一步在药品制备或食品添加剂中使用，其中的使用量可视不同用途有所不同。
制备药物或者化妆品时，天麻素可与常规药物载体，如软膏基质、乳化剂、表面活性剂、渗透剂、稳定剂等制成乳剂或软膏等外用制剂，制备工艺可采用常规的药物制剂制备技术。天麻素在化妆品中或药品中的用量以重量百分比计为0.1～2％比较合适。
酪氨酸酶参与了许多水果蔬菜以及鱼虾等水产品及其加工产品的褐变反应，是导致变褐生斑和黑化而失鲜的主要原因，由于天麻素能够有效抑制酪氨酸酶活性和黑色素形成量，能够在预防褐变的食品添加剂中应用。
综上所述，天麻素具有强烈的酪氨酸酶抑制作用，能显著降低黑色素生成量，而且安全又稳定，可应用于防治老年斑、色斑等皮肤色素沉着和美白，以及作为食品保鲜添加剂。
附图说明
为了更清楚地说明本发明实施例中的技术方案，下面将对实施例描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的有关本发明的附图仅仅是本发明的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他的附图。
图1是天麻素和熊果苷对人HEM细胞内酪氨酸酶抑制活性比较；
图2是不同浓度的天麻素在不同时间对酪氨酸酶活力影响曲线图，天麻素浓度为0(□)mM、8(▼)mM、32(▲)mM、125(●)mM和500(■)mM；
图3是天麻素和熊果苷对人HEM细胞黑素含量影响柱状比较图；
图4是天麻素和熊果苷对人HEM细胞黑化影响直观比较图；
图5是天麻素和熊果苷对人HEM细胞毒性影响柱状比较图。
具体实施方式
下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行详细的描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动的前提下所获得的所有其他实施例，都属于本发明保护的范围。
实验所用试剂和仪器：1640细胞培养液、胰蛋白酶、曲拉通X-100(triton)、胎牛血清(FBS)、左旋多巴(L-dopa)、二甲基亚砜(DMSO)、噻唑兰(MTT)、天麻素(Gastrodin)、熊果苷(Arbutin)、紫外分光光度计、酶联免疫检测仪。
实施例1
天麻素对人黑色素表皮细胞(HEM)内酪氨酸酶抑制活性的测定
1)实验细胞制备
取对数生长期的人HEM细胞传代，待融合成单层时，经0.25wt％的胰蛋白酶消化，用含有10wt％FBS的1640培养液传代，置于5vol％CO2温度为37℃孵箱中进行培养。
2)实验分组
天麻素和熊果苷贮液用细胞培养液新鲜配制，4℃冰箱避光保存一周内使用，实验用时用新鲜培养基调至终浓度。天麻素和熊果苷的实验终浓度分别设定为4mM、8mM、16mM、32mM、64mM，空白对照组仅加入测试药物所用相应培养液。
3)酪氨酸酶抑制活性的测定
以熊果苷作为对照品，方法如下：将配制的细胞悬液调整细胞浓度为2.5×104/ml，每孔200μl接种至96孔板培养过夜后弃培养液，分别用4mM、8mM、16mM、32mM、64mM浓度天麻素和熊果苷的培养液(不含FBS)换液1次,对照组只加培养液，继续培养72h。用pH7.4的PBS洗涤两次,每孔加100μl1wt％triton充分裂解细胞。37℃预热，加入2mM/LL-DOPA溶液100μl/孔，于37℃下反应30min，以490nm波长测定各孔吸光度OD值。每一浓度设3个复孔,取平均值。
酪氨酸酶活性抑制率＝(1-各浓度平均吸光度值÷空白对照组平均吸光度值)×100。
结果如图1所示，由图1可以看出，天麻素与熊果苷相比表现出明显酪氨酸酶活性抑制效果；随着浓度增加到64mM，天麻素的抑制效果更加强烈，几乎达到70％。抑制效果与天麻素具有浓度依赖性。因此，天麻素对酪氨酸酶活性抑制作用优于熊果苷。
实施例2
天麻素对蘑菇酪氨酸酶抑制的时间测定
将蘑菇酪氨酸酶与不同浓度的天麻素(0mM、8mM、32mM、125mM和500mM)在室温下共同孵育，分别在不同时间测定比色皿的吸光度，反应体系为2mM/LL-DOPA溶液。通过检测酶的剩余活力，最终换算酶抑制率。
结果如图2所示，由图2可以看出，在30分钟以内，酪氨酸酶抑制效果达到最大，随着时间延长抑制效果维持恒定不变，说明天麻素具有较好的抑制稳定性。
实施例3
天麻素抑制人HEM黑素细胞黑色素含量的测定
将配制的细胞悬液调整细胞浓度为5×104/ml，接种6孔板，每孔2ml，置于培养箱中培养过夜后，不同浓度天麻素及熊果苷培养液换液，对照组只加培养基；继续培养72h后，收集至无菌EP管中，1000r/min离心5min，冰冷PBS(PH＝7.4)洗涤3次，弃上清。细胞团块中加1mol/LNaOH100μL(含10wt％二甲基亚砜)，蒸馏水加至400μL，吹打均匀后移入96孔板中，每孔加100μL。酶联免疫检测仪测定490nm的A490值，每一浓度设4个复孔。
黑色素形成率＝(各浓度平均吸光度值÷空白对照组平均吸光度值)×100。
结果如图3和图4所示，由图3和图4可以看出，天麻素与熊果苷相比，在4-16mM浓度之间两者差异明显；随着浓度增加到32-64mM时，天麻素表现出强烈抑制黑色素形成，黑色素形成率降至70％左右。因此，天麻素对黑色素形成抑制明显优于熊果苷。
实施例4
天麻素对人HEM细胞的细胞毒性的测定
取对数生长期细胞分散制备单细胞悬液调整细胞浓度为2000/孔，接种96孔板培养过夜后弃培养基，用不同浓度(20mM、30mM、45mM、67mM、100mM)天麻素和熊果苷的培养基换液1次，对照组只加培养基，继续培养72h。临测细胞增殖率时，每孔加20μLMTT溶液(5mg/ml，即0.5wt％的MTT)。置CO2孵箱继续培养4h。此时MTT经线粒体膜琥珀酸脱氢酶转化为甲替，镜下观察细胞内外有大量紫红色针状结晶。小心吸取培养液，每孔加入约150μLDMSO置摇床上低速振荡10min，使甲替结晶完全溶解。立即置酶标仪于490nm测光吸收值A490。
细胞存活率＝(各浓度平均吸光度值÷空白对照组平均吸光度值)×100
结果如图5所示，由图5可以看出，天麻素与熊果苷相比，在0-4mM浓度之间，两者对细胞存活率几乎没有受到影响；在8-128mM浓度之间，随着浓度增加，天麻素对细胞存活率影响显著低于熊果苷。天麻素浓度在64mM以下时几乎没有细胞毒性，说明天麻素安全性明显优于熊果苷。只有当天麻素的浓度高达128mM时，细胞存活率为70％左右。
综上所述，天麻素具有强烈的酪氨酸酶抑制作用，能显著降低黑色素生成量，而且安全又稳定，可应用于防治老年斑、色斑等皮肤色素沉着和美白，以及作为食品保鲜添加剂。
对于本领域技术人员而言，显然本发明不限于上述示范性实施例的细节，而且在不背离本发明的精神或基本特征的情况下，能够以其他的具体形式实现本发明。因此，无论从哪一点来看，均应将实施例看作是示范性的，而且是非限制性的，本发明的范围由所附权利要求而不是上述说明限定，因此旨在将落在权利要求的等同要件的含义和范围内的所有变化囊括在本发明内。不应将权利要求中的任何附图标记视为限制所涉及的权利要求。
此外，应当理解，虽然本说明书按照实施方式加以描述，但并非每个实施方式仅包含一个独立的技术方案，说明书的这种叙述方式仅仅是为清楚起见，本领域技术人员应当将说明书作为一个整体，各实施例中的技术方案也可以经适当组合，形成本领域技术人员可以理解的其他实施方式。
Claims (10)
1.天麻素作为酪氨酸酶抑制剂的应用。
2.天麻素在化妆品中作为美白剂的应用。
3.一种美白化妆品，其特征在于：主要由有效量的天麻素与药学上所允许的辅料或常规药用载体组成。
4.根据权利要求3所述的美白化妆品，其特征在于：还包括内皮素拮抗剂、桑树提取物、甘草提取物、胎盘提取液、果酸、芦荟和L-抗坏血酸中的一种或多种。
5.根据权利要求3所述的美白化妆品，其特征在于：天麻素的含量以重量百分比计为0.01％～2％。
6.天麻素在治疗由酪氨酸酶引起的皮肤色变、雀斑、沉着斑、黄褐斑和色素痣的药物中的应用。
7.一种治疗由酪氨酸酶引起的皮肤色变、雀斑、沉着斑、黄褐斑和色素痣的药物，其特征在于：主要由有效量的天麻素与药学上所允许的辅料或常规药用载体组成。
8.根据权利要求8所述的药物，其特征在于：还包括内皮素拮抗剂、桑树提取物、甘草提取物、胎盘提取液、果酸、芦荟和L-抗坏血酸中的一种或多种。
9.根据权利要求8所述的药物，其特征在于：天麻素的含量以重量百分比计为0.01％～2％。
10.天麻素在食品中作为预防褐变的食品添加剂的应用。
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Cited By (1)
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101332189A (zh) * | 2007-06-26 | 2008-12-31 | 广东东阳光药业有限公司 | 一种改进的天麻素泡腾片及其制备方法 |
-
2015
- 2015-10-26 CN CN201510701308.3A patent/CN105213209A/zh active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101332189A (zh) * | 2007-06-26 | 2008-12-31 | 广东东阳光药业有限公司 | 一种改进的天麻素泡腾片及其制备方法 |
Non-Patent Citations (4)
| Title |
|---|
| 章苏宁等: "《化妆品工艺学》", 30 March 2007 * |
| 裴超俊: "天麻素对酪氨酸酶的抑制作用及黑色素生成的影响", 《中国期刊网中国优秀硕士学位论文全文数据库基础科学辑》 * |
| 陈彤等: "天麻素对B16黑素瘤细胞黑色素形成的影响", 《安徽农业科学》 * |
| 齐向东等: "《微创美容外科学》", 31 December 2012 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108102862A (zh) * | 2018-01-30 | 2018-06-01 | 贵州省普安县普白珍稀资源开发有限公司 | 一种天麻保健酒及其制备方法 |
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