CN111000849A - 羽扇豆醇dyc-6的应用和产品 - Google Patents
羽扇豆醇dyc-6的应用和产品 Download PDFInfo
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- CN111000849A CN111000849A CN201911321978.7A CN201911321978A CN111000849A CN 111000849 A CN111000849 A CN 111000849A CN 201911321978 A CN201911321978 A CN 201911321978A CN 111000849 A CN111000849 A CN 111000849A
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Abstract
本发明涉及药物领域,具体而言,提供了一种羽扇豆醇DYC‑6的应用和产品。本发明提供的羽扇豆醇DYC‑6是发明人从十大功劳叶中首次分离得到的三萜类化合物,同时发明人首次发现该物质可以抑制促炎因子和NO的产生,同时抑制NF‑κB的活化,具有减轻炎症或疼痛的性能,提供了该物质的药物可能,为开发和扩大羽扇豆醇DYC‑6的药物应用提供了基础。
Description
技术领域
本发明涉及药物领域,具体而言,涉及一种羽扇豆醇DYC-6的应用和产品。
背景技术
炎症(inflammation)是机体对刺激的一种防御反应,可以发生在机体各个部位的组织和器官,如结肠炎、肝炎、肺炎等。炎症主要具有红、肿、热等变化,同时伴有发热、白细胞增多等全身反应。通常情况下炎症是有益的,是人体的自动防御反应,但过度的炎症可导致长期、严重的炎症反应,增加各种炎症疾病的病理过程,如关节炎、心血管疾病和阿尔兹海默氏病等。
大量研究表明,炎症因子和促炎介质在炎症的发生和发展过程中发挥了重要作用,过度的炎症会造成细胞和组织的损伤,所以抑制炎症因子和促炎介质对炎症的治疗具有重要意义。
十大功劳是我国传统中药,可以用于治疗各种炎症性疾病,包括肺炎、乳腺炎、类风湿性关节炎等,其抗炎活性显著。目前,大多数研究主要针对于十大功劳属植物的药根碱、小檗碱、巴马亭等生物碱类,而对该属种的非生物碱类化合物研究较少。
有鉴于此,特提出本发明。
发明内容
本发明的第一目的在于提供一种羽扇豆醇DYC-6在制备药物、化妆品或功能食品中的应用,该物质为发明人首次从十大功劳叶中分离出来的一种三萜类化合物。
本发明的第二目的在于提供一种含有羽扇豆醇DYC-6的药物。
为了实现本发明的上述目的,特采用以下技术方案:
一种羽扇豆醇DYC-6在制备抗炎产品中的应用,所述羽扇豆醇DYC-6的结构式如下:
进一步地,所述产品包括药物、化妆品或功能食品。
进一步地,所述药物为抗炎治疗药物。
进一步地,羽扇豆醇DYC-6在制备抑制炎症引发的NF-κB活化表达药物中的应用。
进一步地,羽扇豆醇DYC-6在制备降低炎症所导致的细胞损伤的药物中的应用。
进一步地,羽扇豆醇DYC-6在制备抑制炎症引发的促炎因子表达药物中的应用;
优选地,所述促炎因子包括iNOS、COX-2或TNF-α中的至少一种。
进一步地,抗炎治疗药物所治疗的炎症包括结肠炎、过敏性鼻炎、肝炎、肺炎、骨关节炎、前列腺炎、病毒感染、细菌感染或直肠炎。
一种药物,包括上述羽扇豆醇DYC-6。
进一步地,还包括药学上可接受的载体或辅料。
进一步地,所述药物为口服、局部或皮肤透过用药;
优选地,所述药物的剂型包括片剂、颗粒剂、散剂、胶囊剂、溶液剂、悬浮剂、乳剂或冻干制剂。
与现有技术相比,本发明的有益效果为:
1)本发明提供的羽扇豆醇化合物6β-hydroxy-3-oxo-lup-20(29)-en-28-oicacid(本发明简称为DYC-6)是发明人从十大功劳叶中首次分离得到的三萜类化合物,同时发明人首次发现该物质可以抑制促炎因子和NO的产生,具有减轻炎症或疼痛的性能,提供了该物质的药物可能。
2)本发明中,通过设计体外炎症模型,首次提出并证实了羽扇豆醇DYC-6能够降低细胞损伤,通过阻断NO和细胞促炎因子的产生,以及NF-κB的活化,从而发挥抗炎作用。因而,本发明提供了将羽扇豆醇DYC-6作为抗炎有效治疗药物的应用,为开发和扩大羽扇豆醇DYC-6的药物应用提供了基础。
3)炎症反应是在生物组织中启动以防御有害刺激,包括入侵的微生物、刺激物或有毒化学物质的正常反应。本发明发现NO和促炎因子与炎症的发生密切相关,本发明重点研究NO和促炎因子在降低炎症中的意义,在以RAW264.7细胞为模型的基础上,分析iNOS、TNF-α和COX-2的表达量,并采用不同浓度的羽扇豆醇DYC-6作用于炎症模型上,研究其抗炎作用与其浓度之间的依赖性关系,为炎症的治疗筛选有效的药物浓度,并为抗炎药物寻找与制备提供新的研究思路。
附图说明
为了更清楚地说明本发明具体实施方式或现有技术中的技术方案,下面将对具体实施方式或现有技术描述中所需要使用的附图作简单地介绍,显而易见地,下面描述中的附图是本发明的一些实施方式,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为羽扇豆醇DYC-6对于正常RAW264.7细胞的毒性结果;
图2为羽扇豆醇DYC-6对LPS诱导的RAW264.7细胞产生炎症NO的影响;
图3为羽扇豆醇DYC-6对LPS诱导的RAW264.7巨噬细胞核蛋白c-Jun,c-Fos和NF-κB/P65的影响;
图4为羽扇豆醇DYC-6对LPS诱导的RAW264.7巨噬细胞NF-κB信号通路的影响;
图5为羽扇豆醇DYC-6对LPS诱导的RAW264.7巨噬细胞MAPK信号通路的影响;
图6为羽扇豆醇DYC-6对LPS诱导的RAW264.7巨噬细胞P13-Akt信号通路的影响;
图7为羽扇豆醇DYC-6对LPS诱导的RAW264.7细胞产生促炎细胞因子iNOS的影响;
图8为羽扇豆醇DYC-6对LPS诱导的RAW264.7细胞产生促炎细胞因子TNF-α的影响;
图9为羽扇豆醇DYC-6对LPS诱导的RAW264.7细胞产生促炎细胞因子COX-2的影响。
具体实施方式
下面将结合实施例对本发明的实施方案进行详细描述,但是本领域技术人员将会理解,下列实施例仅用于说明本发明,而不应视为限制本发明的范围。实施例中未注明具体条件者,按照常规条件或制造商建议的条件进行。
除非另有说明,本文中所用的专业与科学术语与本领域熟练人员所熟悉的意义相同。此外,任何与所记载内容相似或均等的方法或材料也可应用于本发明中。
本发明提供的羽扇豆醇DYC-6在制备抗炎产品中的应用,其中,羽扇豆醇DYC-6是发明人从十大功劳叶中首次分离得到的三萜类化合物,结构式如下:
羽扇豆醇DYC-6是从十大功劳叶的二氯甲烷段分离出来的三萜类化合物,该有效部位富含三萜类成分,但未发现生物碱类化合物,羽扇豆醇DYC-6是否具有抗炎活性,还没有相关的研究报道。有鉴于在领域的研究空白,发明人首次发现该物质可以抑制促炎因子和NO的产生,具有减轻炎症或疼痛的性能,提供了该物质的药物可能。
本发明中,经细胞诱导模型实验发现,羽扇豆醇DYC-6具有抗炎的功效。羽扇豆醇DYC-6可以通过抑制由LPS刺激巨噬细胞所产生促炎因子和NF-κB/P65转录因子的活化,起到抗炎的作用。
实验研究还发现,羽扇豆醇DYC-6通过抑制LPS诱导巨噬细胞产生过量NO关键酶,起到抗炎作用,这有望成为新型抗炎治疗的有效途径。
在优选地实施方式中,产品包括药物、化妆品或功能食品。
在优选地实施方式中,药物为抗炎治疗药物。具体地,抑制由炎症所引发的NF-κB活化表达药物,和/或,降低炎症所导致细胞损伤药物,和/或,抑制由炎症引发的促炎因子表达药物。其中,促炎因子包括iNOS、COX-2或TNF-α中的至少一种。
在优选地实施方式中,抗炎治疗药物所治疗的炎症包括结肠炎、过敏性鼻炎、肝炎、肺炎、骨关节炎、前列腺炎、病毒感染、细菌感染或直肠炎。
一种包括羽扇豆醇DYC-6的药物。优选地,该药物还可以包括药学上可接受的载体或辅料。辅料可以包括润滑剂、溶剂、湿润剂、表面活性剂以及胶凝剂等等,本领域技术人员可以根据目标药物的剂型和用药方式等等参照本领域常规技术方式得到含有羽扇豆醇DYC-6的药物,这些都属于本申请的保护范围。
润滑剂,如硬脂醇、单蓖麻醇酸甘油酯、单硬酯酸甘油酯、丙-1,2-二醇、丁-1,3-二醇、十六烷醇、异硬酯酸异丙酯、硬酯酸、棕榈酸异丁酯、硬酯酸异十六烷基酯、油醇、月桂酸异丙酯、月桂酸己酯等等。
溶剂,如水、二氯甲烷、异丙醇、蓖麻油、乙二醇单乙醚、二乙二醇单丁基醚、二乙二醇单乙基醚、二甲亚砜、四氢呋喃、植物油和动物油等等。
湿润剂,如丙三醇、山梨醇、2-吡咯烷酮-5-羧酸钠、可溶胶原、邻苯二甲酸二丁酯等等。
表面活性剂,例如乙二醇和乙二醇酯、聚乙二醇醚和酯、糖醚和酯、金属皂、硫酸化脂族醇、硫酸烷基醚、硫酸化油类等等。
胶凝剂,如果胶、凝胶及其衍生物、甲基纤维素、羧甲基纤维素或氧化纤维素、纤维素胶、瓜耳豆胶、阿拉伯树胶、刺梧桐树胶、黄芪胶、膨润土、琼脂、海藻酸盐、卡波姆、白明胶、泡叶藻、长角豆等等。
在优选地实施方式中,药物为口服、局部或皮肤透过用药。药物的剂型可以为片剂、颗粒剂、散剂、胶囊剂、溶液剂、悬浮剂、乳剂或冻干制剂。
下面通过具体的实施例进一步说明本发明,但是,应当理解为,这些实施例仅仅是用于更详细地说明之用,而不应理解为用于以任何形式限制本发明。
实施例1 MTT法检测羽扇豆醇DYC-6对于正常RAW264.7细胞的毒性作用
实验材料:RAW264.7巨噬细胞购于美国细胞保藏中心(ATCC)。
实验步骤:将处于对数生长期的RAW264.7巨噬细胞,以10%胎牛血清,100μg/mL链霉素,和100units/mL盘尼西林的RPMI medium 1640培养基将细胞吹打至单个细胞;重悬后,以1×106细胞/mL接种于96-平板中,按照不同的实验组进行加药处理。其中,空白组是不含有RAW264.7细胞的RPMI medium 1640完全培养基;对照组是不含有羽扇豆醇DYC-6和LPS的细胞培养液;实验组是分别加入10,20,40,60,80,100μM羽扇豆醇DYC-6的细胞培养液,每组三个重复。
各组培养液在CO2培养箱培养24h,然后将培养液吸走,加入以终浓度为0.5mg/mL的MTT溶液100μL,继续放入CO2培养箱孵育4h后,加入等体积的MTT终止液,继续培养16-20h后,采用酶标仪在波长为550nm处测定每孔的吸光度,并按照公式计算出细胞的存活率。计算公式为:
细胞存活率=(A实验组-A空白组)/(A对照组-A空白组)×100%,A为检测波长为550nm处的吸光度。
实验结果如图1所示,由图1结果可知,在10-100μM的羽扇豆醇DYC-6处理细胞后,细胞存活率均在92%以上,说明羽扇豆醇DYC-6对RAW264.7巨噬细胞均无显著性毒性。
实施例2 NO释放量的检测
实验步骤:(1)标准曲线的制作
将1M的亚硝酸钠标准液,用ddH2O将标准液对比稀释成100、50、25、12.5、6.25、3.125、1.5625、0μM的溶液梯度,分别取100μL到96孔板中,每个浓度三个重复,然后每孔加入100μL按1:1比例配置好的Griess试剂室温放置10min后,在570nm处测其吸光度,制作标曲。
(2)取对数生长期的RAW264.7巨噬细胞,以1×106cells/ml密度接种于96孔板中,在细胞培养箱中培养18小时。
(3)RAW264.7巨噬细胞经不同浓度的DYC-6预处理30min,分别于LPS(1μg/ml)共同孵育24小时,然后每孔吸取100μL上清另一96孔板中,加入100μL的GriessA、B混合液,室温静置10min,用酶标仪在波长为570nm处测其吸光度,带入标曲,测得NO含量。
实验结果如图2所示,RAW264.7巨噬细胞能显著抑制LPS诱导RAW264.7巨噬细胞所引起的NO含量。
实施例3 RAW264.7巨噬细胞对LPS诱导的RAW264.7巨噬细胞对核转位的调控
实验步骤:采用Western blot实验观察在指定时间点对LPS诱导的RAW264.7细胞核蛋白中c-Jun,c-Fos和NF-κB/P65的影响。细胞分组设置:正常对照组,LPS(1μg/ml10min,30min,60min)诱导组,LPS+DYC-6(80μM10min,30min,60min)药物治疗组。
细胞药物处理结束后,收集细胞提取细胞中的核蛋白,Bradford法对蛋白进行定量,在Western blot下检测细胞核蛋白中c-Jun,c-Fos和NF-κB/P65蛋白表达量。
实验结果见图3所示,检测了核蛋白中c-Jun和c-Fos的表达,发现DYC-6预处理细胞并不能抑制LPS诱导引起的c-Jun和c-Fos的转录,进而不能抑制AP-1的活化。但DYC-6预处理能显著抑制NF-κB/P65的增加,证明了DYC-6能通过抑制NF-κB的激活,从而抑制LPS诱导RAW264.7巨噬细胞NF-κB/P65的核移位。
实施例4 DYC-6对LPS诱导的RAW264.7巨噬细胞NF-κB信号通路的影响
实验步骤:采用Western blot实验观察在指定时间点对LPS诱导的RAW264.7细胞中IκB和IKK蛋白磷酸化的影响。细胞分组设置:正常对照组,LPS(1μg/ml 10min,30min,60min)诱导组,LPS+DYC-6(80μM 10min,30min,60min)药物治疗组。
细胞药物处理结束后,收集细胞提取细胞中的全蛋白,Bradford法对蛋白进行定量,在Western blot下检测细胞中IκB和IKK蛋白表达量。
实验结果见图4所示,对照组RAW264.7巨噬细胞IκB和IKK蛋白表达量最高,LPS刺激10min后,IκB蛋白表达量最低,与空白对照组有显著性差异,表明LPS可以显著诱导IκB和IKK磷酸化,使IκB降解。DYC-6预处理RAW264.7细胞30min,在LPS刺激细胞30min和60min时明显抑制IκB和IKK蛋白的表达。表明DYC-6可以通过抑制LPS诱导IκB和IKK的磷酸化,从而抑制IκB降解,使IκB蛋白维持在一个较高水平。
实施例5 DYC-6对LPS诱导的RAW264.7巨噬细胞MAPK信号通路的影响
药物处理过程如实施例3所详述。检测了DYC-6对LPS诱导的RAW264.7细胞中ERK,JNK和P38蛋白磷酸化的影响。
结果见图5,由图5结果可知,对照组RAW264.7巨噬细胞内磷酸化ERK1/2,JNK和P38蛋白量表达较低,LPS处理后磷酸化的ERK1/2和JNK蛋白表达上升,从而激活MAPK信号通路,而80μM DYC-6和蛋白共同作用细胞时,在10min时细胞内的磷酸化ERK和JNK蛋白表达明显被抑制,在30min时,DYC-6只对磷酸化P38的表达有明显的抑制作用,在处理的整个过程中,DYC-6的预处理在三个时间点内对P38的磷酸化均没有抑制效果,表明DYC-6能在特定时间点抑制LPS诱导的ERK1/2和INK蛋白的磷酸化。
实施例6 DYC-6对LPS诱导的RAW264.7巨噬细胞P13-AKT信号通路的影响
药物处理过程如实施例3所详述。检测了DYC-6对LPS诱导的RAW264.7细胞中P85,Akt和PDK1蛋白磷酸化的影响。
结果见图6,由图6结果可知,对照组RAW264.7巨噬细胞内磷酸化P85,Akt和PDK1蛋白量表达较低,LPS处理后磷酸化的Akt蛋白表达上升,从而激活P13/Akt信号通路,而DYC-6(80μM)和LPS(1μg/ml)共同作用细胞时,在三个时间点(10min,30min,60min)时细胞内的磷酸化Akt蛋白表达明显被抑制。表明DYC-6能在特定时间点抑制LPS诱导的Akt的磷酸化。
实施例7 DYC-6对LPS诱导的RAW264.7巨噬细胞产生促炎因子表达的影响
药物处理过程如实施例3所详述。细胞处理结束后,使用Trozol法提取总量RNA,使用RevertAid First Strand cDNA Synthesis Kit(Thermo)反转录获得cDNA。用qPCRMaster Mix和特异性合成引物进行荧光定量PCR检测。数据使用-ΔΔCq法与GAPDH对比分析。
实验结果如图7、8、9所示,由图7、8、9结果可知,正常对照组中iNOS、COX-2和TNF-αmRNA表达量很低,LPS诱导RAW264.7细胞促使细胞内iNOS、COX-2和TNF-αmRNA表达量明显升高,40μM和80μM DYC-6处理能显著降低iNOS、COX-2和TNF-αmRNA的表达水平。由此表明,DYC-6处理组能有效抑制iNOS、COX-2和TNF-αmRNA表达并呈剂量依赖性。
由如上实施例1-7的实验结果可知,DYC-6能够降低LPS所引起的炎症反应。在以DYC-6进行预处理后,NF-κB发生核移位的行为减少,更加能够证实DYC-6对于LPS所诱导RAW264.7巨噬细胞产生的炎症模型具有显著的抗炎作用,也为DYC-6作为抗炎治疗剂的应用提供了理论依据。
尽管已用具体实施例来说明和描述了本发明,然而应意识到,在不背离本发明的精神和范围的情况下可以作出许多其它的更改和修改。因此,这意味着在所附权利要求中包括属于本发明范围内的所有这些变化和修改。
Claims (10)
2.根据权利要求1所述的应用,其特征在于,所述产品包括药物、化妆品或功能食品。
3.根据权利要求2所述的应用,其特征在于,所述药物为抗炎治疗药物。
4.根据权利要求3所述的应用,其特征在于,羽扇豆醇DYC-6在制备抑制炎症引发的NF-κB活化表达药物中的应用。
5.根据权利要求3所述的应用,其特征在于,羽扇豆醇DYC-6在制备降低炎症所导致的细胞损伤的药物中的应用。
6.根据权利要求3所述的应用,其特征在于,羽扇豆醇DYC-6在制备抑制炎症引发的促炎因子表达药物中的应用;
优选地,所述促炎因子包括iNOS、COX-2或TNF-α中的至少一种。
7.根据权利要求3所述的应用,其特征在于,抗炎治疗药物所治疗的炎症包括结肠炎、过敏性鼻炎、肝炎、肺炎、骨关节炎、前列腺炎、病毒感染、细菌感染或直肠炎。
8.一种药物,其特征在于,包括权利要求1所述的羽扇豆醇DYC-6。
9.根据权利要求8所述的药物,其特征在于,还包括药学上可接受的载体或辅料。
10.根据权利要求8所述的药物,其特征在于,所述药物包括口服用药、局部用药或皮肤透过用药;
优选地,所述药物的剂型包括片剂、颗粒剂、散剂、胶囊剂、溶液剂、悬浮剂、乳剂或冻干制剂。
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1793161A (zh) * | 2005-12-31 | 2006-06-28 | 中国海洋大学 | 桦木属植物中提取羽扇豆醇的方法 |
CN102497872A (zh) * | 2009-07-18 | 2012-06-13 | 加的夫大学学院咨询有限公司 | 炎症性疾病的抑制剂 |
CN103936812A (zh) * | 2014-04-29 | 2014-07-23 | 中国科学院昆明植物研究所 | 羽扇豆烷型三萜类化合物及其药物组合物和其应用 |
CN110139643A (zh) * | 2017-01-07 | 2019-08-16 | 居伊福斯坦·蒙卡姆尼楚 | 一种用于治疗代谢紊乱综合征、炎症及其并发症的药物成分 |
CN110585216A (zh) * | 2019-09-03 | 2019-12-20 | 南方医科大学 | 羽扇豆醇在制备预防或治疗肝损伤药物中的应用 |
-
2019
- 2019-12-19 CN CN201911321978.7A patent/CN111000849A/zh active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1793161A (zh) * | 2005-12-31 | 2006-06-28 | 中国海洋大学 | 桦木属植物中提取羽扇豆醇的方法 |
CN102497872A (zh) * | 2009-07-18 | 2012-06-13 | 加的夫大学学院咨询有限公司 | 炎症性疾病的抑制剂 |
CN103936812A (zh) * | 2014-04-29 | 2014-07-23 | 中国科学院昆明植物研究所 | 羽扇豆烷型三萜类化合物及其药物组合物和其应用 |
CN110139643A (zh) * | 2017-01-07 | 2019-08-16 | 居伊福斯坦·蒙卡姆尼楚 | 一种用于治疗代谢紊乱综合征、炎症及其并发症的药物成分 |
CN110585216A (zh) * | 2019-09-03 | 2019-12-20 | 南方医科大学 | 羽扇豆醇在制备预防或治疗肝损伤药物中的应用 |
Non-Patent Citations (1)
Title |
---|
SHEHATA等: "Anti-inflammatory activity of Kleinia odora", 《EUROPEAN JOURNAL OF INTEGRATIVE MEDICINE》 * |
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