CN113304130A - 甘草查尔酮a在制备抗类过敏药物中的应用 - Google Patents
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Abstract
本发明公开了甘草查尔酮A在制备抗类过敏药物中的应用,通过比较KU812细胞脱颗粒、足趾肿胀程度、足趾伊文斯蓝渗出程度、血清TNF‑α释放量以评价待测药物组、生理盐水对照组及正常对照组,以评价药物对类过敏性疾病的治疗效果,确定甘草查尔酮A能够用于抗类过敏药物的制备。甘草查尔酮A能够有效减轻小鼠局部及系统性类过敏反应症状;减少肥大细胞脱颗粒,对类过敏引起的症状具有显著改善作用。
Description
技术领域
本发明属于生物医药技术领域,具体涉及甘草查尔酮A在制备抗类过敏药物中的应用。
背景技术
类过敏反应不是免疫应答反应,与过敏反应的病因和发生机制截然不同。免疫学中,将抗原(或半抗原)再次进入致敏的机体与其特异性抗体相结合而激发的不良反应,称为过敏反应。过敏反应需要重复暴露于抗原中,首次暴露时,通过引起体内淋巴细胞对抗原产生特异性IgE而完成致敏过程;当机体再次暴露于抗原时,抗原与肥大细胞表面的IgE结合而引起过敏反应的发生,是免疫应答反应。而类过敏反应的发生,不需要提前接触抗原的致敏过程,抗体或淋巴细胞不参与反应的发生,无需IgE等免疫球蛋白介导,首次暴露于抗原下即可迅速发生。
类过敏反应与肥大细胞或嗜碱性粒细胞脱颗粒、激活补体系统,引起释放组胺或其他血管活性因子等生物活性介质有关。肥大细胞上MrgprX2受体,被认为是类过敏反应发生的重要受体,可被SP、C3a、C48/80及吗啡等多种抗生素、肌松剂等物质直接激活引发类过敏反应。因此,MrgprX2受体可以作为类过敏反应的潜在治疗靶点。
近年来,临床上类过敏性疾病的发生愈发常见,诸如过敏性皮炎、过敏性休克等疾病,患者血清IgE未升高且多病情危急。目前针对此类疾病的药物均是在过敏反应机制下游的症状控制阶段作用,肥大细胞等释放的致敏介质仍存在于体内,具有潜在毒性。以IgE为靶标的单克隆抗体对此类疾病也无明显疗效。长期使用上述药物会引起多种不良反应。
甘草为豆科植物甘草的干燥根和根茎,其味甘,平,归心、肺、脾、胃经,具有补脾益气、清热解毒、祛痰止咳、缓急止痛、调和诸药的功效。甘草中主要含有三萜皂苷类、黄酮类和多糖类成分,临床上以生品和炮制品入药。甘草经炮制后理化性质、性味功效等发生了改变。生甘草性味甘偏凉,常被用于清热解毒、化痰止咳,蜜炙后性味甘温,有补脾益气的功效。
甘草查尔酮A(licochalcone A)是从甘草属植物中分离纯化的黄酮类化合物。现有技术研究成果显示,甘草查尔酮A有抗炎、抗癌、抗肿瘤、抑菌、体内代谢和抗疟抗寄生虫等方面的作用,但是并未见其关于抗类过敏反应相关的报道。
发明内容
为了克服上述现有技术的缺点,本发明的目的在于提供甘草查尔酮A在制备抗类过敏药物中的应用。
为了达到上述目的,本发明采用以下技术方案予以实现:
本发明公开了甘草查尔酮A在制备抗类过敏的药物中的应用。
优选地,所述的药物为降低类过敏反应细胞脱颗粒的药物。
进一步优选地,所述的药物为抑制Substance P引发的KU812细胞脱颗粒的药物。
优选地,所述的药物为降低局部皮肤类过敏反应炎性浸润的药物。
进一步优选地,甘草查尔酮A呈剂量依赖性地抑制局部皮肤类过敏性反应。
优选地,所述的药物为抑制炎症因子释放的药物。
进一步优选地,甘草查尔酮A呈剂量依赖性地抑制血清TNF-α释放。
优选地,所述的药物为减轻全身性过敏的药物。
优选地,所述的药物用于抑制类过敏反应时,动物给药量为10-100mg/kg。
本发明还公开了甘草查尔酮A在制备治疗过敏性皮炎或过敏性休克的药物中的应用。
与现有技术相比,本发明具有以下有益效果:
本发明公开了甘草查尔酮A制备抗类过敏药物的制药应用,对于改善类过敏性症状有明确的治疗效果,通过比较KU812细胞脱颗粒、足趾肿胀程度、足趾伊文斯蓝渗出程度、足部皮肤组织切片HE染色、血清组胺释放量及体温下降程度,评价待测药物组、生理盐水对照组及正常对照组,以评价药物对类过敏性疾病的治疗效果,确定甘草查尔酮A能够用于类抗过敏药物的制备。甘草查尔酮A能够有效减轻小鼠局部及系统性类过敏反因症状;减少肥大细胞脱颗粒,对类过敏引起的症状具有显著改善作用。
附图说明
图1为甘草查尔酮A对SP引发的KU812细胞脱颗粒的抑制结果图;
图2为甘草查尔酮A对SP引发的C57小鼠足趾肿胀的抑制结果图;
图3为甘草查尔酮A对SP引发的C57小鼠足趾伊文思蓝渗出的抑制结果图;
图4为甘草查尔酮A对SP引发的C57小鼠血清TNF-α含量的抑制结果图。
具体实施方式
为了使本技术领域的人员更好地理解本发明方案,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清楚、完整地描述,显然,所描述的实施例仅仅是本发明一部分的实施例,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前提下所获得的所有其他实施例,都应当属于本发明保护的范围。
需要说明的是,本发明的说明书和权利要求书及上述附图中的术语“第一”、“第二”等是用于区别类似的对象,而不必用于描述特定的顺序或先后次序。应该理解这样使用的数据在适当情况下可以互换,以便这里描述的本发明的实施例能够以除了在这里图示或描述的那些以外的顺序实施。此外,术语“包括”和“具有”以及他们的任何变形,意图在于覆盖不排他的包含,例如,包含了一系列步骤或单元的过程、方法、系统、产品或设备不必限于清楚地列出的那些步骤或单元,而是可包括没有清楚地列出的或对于这些过程、方法、产品或设备固有的其它步骤或单元。
下面结合附图对本发明做进一步详细描述:
实施例1甘草查尔酮A抑制SP引发的KU812细胞β氨基己糖苷酶释放
1、实验材料
SP(购于MCE公司),KU812细胞,RPMI1640培养基(含有青霉素100U/mL,链霉素0.1mg/mL,20%FBS),台氏液,甘草查尔酮A(购于宝鸡辰光公司),0.1MNa2CO3,0.1M NaHCO3,β氨基己糖苷酶,0.1M柠檬酸,0.1M柠檬酸钠。
所用的SP(Substance P)是指由Von Euler和Gaddum于1931发现的神经肽,序列为Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2,分子量为1340。
进一步,SP的纯度≥97%。
所述甘草查尔酮A的结构式如下:
2、实验方法
将KU812细胞接种于96孔板中(1×105个/孔),离心弃培养基。用无菌台氏液配制甘草查尔酮A溶液(浓度分别为0μM,12.5μM,25μM和50μM),分别加入对应的孔板中,并设置空白对照组。药物孵育30min。用含有30μg/mLSP的台氏液配置上述浓度甘草查尔酮A溶液,并加入相应孔板内。激动30min。离心,每孔取50μL上清,分别加入干净孔中。将空白对照组孔中的上清完全移除,每孔加入100μL 0.1%Triton,反复吹打,用于裂解细胞。离心,取50μL裂解液上清,加入干净孔中。向所有孔中均加入50μLβ氨基己糖溶液,37℃孵育1.5小时。0.1M NaHCO3:0.1M Na2CO3(1:9)用于中止反应。405nm波长测吸光度。
3、实验结果
结果参见图1,图1中,横坐标为浓度,纵坐标为β氨基己糖苷酶释放百分比;从图1中可以看出,相对于空白对照组,30μg/mL的SP可以显著性引起KU812细胞脱颗粒,释放β氨基己糖苷酶,且随着浓度增大,甘草查尔酮A可以剂量依赖性地抑制KU812释放β氨基己糖苷酶。
实施例2甘草查尔酮A抑制SP引起的小鼠足趾肿胀、伊文思蓝渗出
1、实验材料
SP(购于MCE公司),6-8周龄雄性C57小鼠(购于西安交通大学实验动物中心),甘草查尔酮A(购于宝鸡辰光),0.4%伊文思蓝溶液,3.5%水合氯醛溶液,PBS溶液,生理盐水,丙酮。
2、实验方法
将小鼠分为空白对照组、阳性对照组和各浓度的甘草查尔酮A给药组。用0.5%CMC-Na溶液配制不同浓度的甘草查尔酮A溶液(分别为20mg/kg,40mg/kg,80mg/kg)灌胃给药。30min后,3.5%的水合氯醛溶液麻醉小鼠,尾静脉注射0.4%伊文思蓝溶液。测量各组小鼠左右脚掌的厚度,随后用微量注射器在左脚掌皮下5μL浓度为30μg/mL的SP溶液,右脚掌皮下等体积的PBS溶液。15分钟后,处死小鼠。再次测量各组小鼠脚掌厚度。剪下小鼠足部,烘干,称量重量。破碎足趾,用丙酮:生理盐水(7:3)溶解足趾中的伊文思蓝,并在620nm处测量吸光度,计算单位体积吸光度。
3、实验结果
结果参见图2、3。图2、3中,横坐标为浓度,纵坐标为组织肿胀百分比或伊文思蓝渗出程度;图2、3中可见,相对于空白对照组,30μg/mL的SP可以显著性引起C57小鼠足趾肿胀及伊文思蓝渗出,说明随着浓度增大,甘草查尔酮A可以剂量依赖性地抑制C57小鼠足趾局部类过敏性反应。
实施例3甘草查尔酮A抑制SP引起的小鼠血清TNF-α含量升高
1、实验材料
SP(购于MCE公司),6-8周龄雄性C57小鼠(购于西安交通大学实验动物中心),甘草查尔酮A(购于宝鸡辰光),小鼠TNF-αELISA试剂盒(购于北京义翘)。
2、实验方法
将小鼠分为空白对照组、阳性对照组和各浓度的甘草查尔酮A给药组。用0.5%CMC-Na溶液配制不同浓度的甘草查尔酮A溶液(分别为20mg/kg,40mg/kg,80mg/kg)灌胃给药。30min后,尾静脉注射30μg/mLSP溶液,空白对照组注射等体积生理盐水。1h后,取血,10000g 10min离心,取血清。
按照ELISA试剂盒说明书指示的方法检测小鼠血清TNF-α含量。
3、实验结果
结果参见图4,图4中,横坐标为浓度,纵坐标为血清组胺释放量,相对于空白对照组,30μg/mL的SP可以显著性引起C57小鼠血清TNF-α释放,说明甘草查尔酮A可以剂量依赖性地抑制C57小鼠血清TNF-α释放。
实施例4甘草查尔酮A抑制SP引起的小鼠体温下降
1、实验材料
SP(购于MCE公司),6-8周龄雄性C57小鼠(购于西安交通大学实验动物中心),甘草查尔酮A(购于宝鸡辰光),小鼠体温仪。
2、实验方法
将小鼠分为空白对照组、阳性对照组和各浓度的甘草查尔酮A给药组。用0.5%CMC-Na溶液配制不同浓度的甘草查尔酮A溶液(分别为20mg/kg,40mg/kg,80mg/kg)灌胃给药。30min后,尾静脉注射30μg/mLSP溶液,空白对照组注射等体积生理盐水。每3分钟检测一次小鼠肛温,累计检测30分钟。
3、实验结果
相对于空白对照组,30μg/mL的SP可以显著性引起C57小鼠体温下降,甘草查尔酮A可以剂量依赖性地抑制C57小鼠体温下降,防止小鼠出现过敏性休克。
以上内容仅为说明本发明的技术思想,不能以此限定本发明的保护范围,凡是按照本发明提出的技术思想,在技术方案基础上所做的任何改动,均落入本发明权利要求书的保护范围之内。
Claims (10)
1.甘草查尔酮A在制备抗类过敏的药物中的应用。
2.如权利要求1所述的应用,其特征在于,所述的药物为降低类过敏反应细胞脱颗粒的药物。
3.如权利要求2所述的应用,其特征在于,所述的药物为抑制Substance P引发的KU812细胞脱颗粒的药物。
4.如权利要求1所述的应用,其特征在于,所述的药物为降低局部皮肤类过敏反应炎性浸润的药物。
5.如权利要求4所述的应用,其特征在于,甘草查尔酮A呈剂量依赖性地抑制局部皮肤类过敏性反应。
6.如权利要求1所述的应用,其特征在于,所述的药物为抑制炎症因子释放的药物。
7.如权利要求6所述的应用,其特征在于,甘草查尔酮A呈剂量依赖性地抑制血清TNF-α释放。
8.如权利要求1所述的应用,其特征在于,所述的药物为减轻全身性过敏的药物。
9.如权利要求1~8中任意一项所述的应用,其特征在于,所述的药物用于抑制类过敏反应时,动物给药量为10-100mg/kg。
10.甘草查尔酮A在制备治疗过敏性皮炎或过敏性休克的药物中的应用。
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WO2021055785A1 (en) * | 2019-09-18 | 2021-03-25 | Pharma Cosmetix Research, Llc | Endocannabinoid mimetic and anti-inflammatory compound containing compositions, methods of preparation and uses thereof |
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WO2021055785A1 (en) * | 2019-09-18 | 2021-03-25 | Pharma Cosmetix Research, Llc | Endocannabinoid mimetic and anti-inflammatory compound containing compositions, methods of preparation and uses thereof |
Non-Patent Citations (3)
Title |
---|
GABSIK YANG ETAL.: "Licochalcone A attenuates acne symptoms mediated by suppression of NLRP3 inflammasome", 《PHYTOTHERAPY RESEARCH》 * |
LU WANG ETAL.: "Anti-pseudo-allergic Components in Licorice Extract Inhibit Mast Cell Degranulation and Calcium Influx", 《RESEARCH SQUARE》 * |
李德华,李德宇,李永光: "甘草化学成分与药理作用研究进展", 《中医药信息》 * |
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