CN115040508A - 吲哚-3-乙醛在制备新型抗肥胖活性制剂中的应用 - Google Patents

吲哚-3-乙醛在制备新型抗肥胖活性制剂中的应用 Download PDF

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CN115040508A
CN115040508A CN202210900480.1A CN202210900480A CN115040508A CN 115040508 A CN115040508 A CN 115040508A CN 202210900480 A CN202210900480 A CN 202210900480A CN 115040508 A CN115040508 A CN 115040508A
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indole
acetaldehyde
differentiation
precursor
obesity
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徐丽玲
董晓华
赵璟
高建芳
张中晓
王星云
郭锡熔
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Shanghai Tong Ren Hospital
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Abstract

本发明公开了一种吲哚‑3‑乙醛在制备新型抗肥胖活性制剂中的应用，活性成分为吲哚‑3‑乙醛。采用终浓度为100μM的吲哚‑3‑乙醛可以显著抑制人内脏前体脂肪细胞的分化，抑制人内脏前体脂肪细胞分化成脂水平。因此，吲哚‑3‑乙醛可作为活性制剂，抑制脂肪前体细胞分化及制备抗肥胖的药物和试剂中。

Description

吲哚-3-乙醛在制备新型抗肥胖活性制剂中的应用
技术领域
本发明属药物新应用，特别涉及应用于肥胖领域的活性制剂。
背景技术
肥胖，是由遗传和环境因素共同导致的慢性代谢性疾病，具体由体内总脂肪含量过多和/或局部脂肪含量过多或分布异常引起的。大量研究指出，肥胖除却降低人们的生活质量外，肥胖人群患病(例如，糖尿病、心脏病、高血压等)概率还会大大增加。据报道，我国已有超过一半的成年人患有超重或肥胖，肥胖，已然成为我国亟待解决的公共卫生问题之一。
目前膳食指导、行为疗法及运动疗法是肥胖常规干预手段，但却存在见效慢、持续时间长从而难以坚持；手术治疗虽然凑效快，但存在手术费用高且有术后并发症等风险从而难以普及；药物治疗可以作为肥胖治疗的有效治疗方式，而我国唯一批准的化学减肥药是奥利司他，它是一种长效的特异性胃肠道脂肪酶抑制剂，通过减少人体脂肪吸收，进而控制体重。但其也存在着诸多弊端，比如减肥效果有限，且存在胃肠道不良反应以及可能存在肝损伤等药物毒副作用。
吲哚-3-乙醛(Indole-3-acetaldehyde)作为色氨酸代谢衍生物，其中吲哚-3-乙醛的分子量为159.18，化学式为:C10H9NO，其化学结构式如下式1所示。
Figure BDA0003770681130000011
吲哚-3-乙醛，属于3-烷基吲哚类有机化合物。吲哚-3-乙醛存在于所有物种中。在人类体内，吲哚-3-乙醛参与许多酶促反应。其中，色胺可以生物合成吲哚乙醛；它由kynurenine 3-单加氧酶介导。此外，吲哚乙醛可在醛脱氢酶的作用下转化为吲哚乙酸。在人体中，吲哚乙醛参与色氨酸代谢。至今尚未明确其是否参与脂肪合成。
发明内容
发明目的：为了克服现有技术中存在的不足，本发明提供一种新型抗肥胖的活性制剂的应用。
技术方案：本发明提供了吲哚-3-乙醛在制备新型抗肥胖活性制剂中的应用。
有益效果：一种新型抗肥胖的活性制剂的应用，具体涉及到吲哚-3-乙醛在制备抗肥胖活性制剂中的应用。其中100μM吲哚-3-乙醛可以显著抑制人内脏前体脂肪细胞的分化，抑制人内脏前体脂肪细胞分化成脂水平。因此，吲哚-3-乙醛在抑制脂肪前体细胞分化，抗肥胖的药物和试剂中应用。
附图说明
图1.吲哚-3-乙醛对人脂肪前体细胞活性的影响。
图2.吲哚-3-乙醛对人脂肪前体细胞分化的影响。
图3.吲哚-3-乙醛对人脂肪前体细胞成脂的影响。
图4.吲哚-3-乙醛对人脂肪前体细胞分化关键基因PPARγ信号通路相关标记基因mRNA及蛋白水平表达的影响。
具体实施方式
下面结合附图对本发明作更进一步的说明。
实施例1
吲哚-3-乙醛对人脂肪前体细胞活性无影响
以人内脏前体脂肪细胞为研究对象，取吲哚-3-乙醛标准品，设置10μM、100μM、1000μM浓度吲哚-3-乙醛处理人内脏前体脂肪细胞，检测吲哚-3-乙醛对人内脏前体脂肪细胞活性影响。
试验方法：提前将人内脏前体脂肪细胞接种至96孔板中，待接种24小时后，采用终浓度为10μM、100μM、1000μM浓度的吲哚-3-乙醛(溶解于DMSO)和溶剂(DMSO)对照组处理，待处理的0小时、24小时、48小时及72小时，采用CCK8商业试剂盒检测细胞活性。
检测结果如图1所示，100μM浓度的吲哚-3-乙醛连续处理人内脏前体脂肪细胞，对细胞活性并无影响。后续实验采用100μM浓度的吲哚-3-乙醛进行试验。
实施例2
吲哚-3-乙醛对人内脏前体脂肪细胞的分化影响
以人内脏前体脂肪细胞为研究对象，对人内脏前体脂肪细胞采用如下诱导方案：采用诱导分化培养基I，持续处理4天；换诱导分化培养基II，持续处理4天；其中，诱导分化培养基I配方(100mL体系)如下：IBMX：称取11.5mg，加入500μL的KOH助溶；胰岛素：500nM；地塞米松：1μM；罗格列酮：1μM；P/S(青链霉素混合液)：5％；诱导分化培养基II配方(100mL体系)如下：胰岛素：100nM；P/S：5％。
待人内脏前体脂肪细胞汇合度达到90％以上，以100μM吲哚-3-乙醛加入到诱导分化培养基中培养人内脏前体脂肪细胞，间隔1天换一次添加吲哚-3-乙醛的诱导分化培养基，细胞培养7天，从第二天起，对培养皿中的细胞进行光镜观察，记录其分化情况，并拍照记录。
吲哚-3-乙醛对人内脏前体脂肪细胞的分化影响如图2所示，100μM吲哚-3-乙醛可显著抑制人内脏前体脂肪细胞分化。
实施例3
吲哚-3-乙醛对人内脏前体脂肪细胞的成脂的影响
以人内脏前体脂肪细胞为研究对象，以100μM浓度的吲哚-3-乙醛加入诱导培养基中，利用诱导脂肪细胞分化培养基培养人前体脂肪细胞以诱发人内脏前体脂肪细胞分化，在人内脏前体脂肪细胞分化过程中每隔一天向诱导分化培养基中添加吲哚-3-乙醛干预，分化8天后，利用油红O染色和甘油三酯含量测定评估吲哚-3-乙醛对脂肪细胞成脂的影响。
检测结果如图4所示，油红O结果显示100μM吲哚-3-乙醛可显著抑制人内脏前体脂肪细胞分化成脂水平，甘油三酯含量测定结果显示吲哚-3-乙醛可显著降低人内脏前体脂肪细胞分化的甘油三酯含量。
实验例4
吲哚-3-乙醛对人内脏前体脂肪细胞的分化关键基因CEBPα及PPARγ信号通路相关标记基因蛋白水平表达的影响
以人内脏前体脂肪细胞为研究对象，以100μM浓度的吲哚-3-乙醛加入诱导培养基中，利用诱导脂肪细胞分化培养基培养人前体脂肪细胞以诱发人内脏前体脂肪细胞分化，在人内脏前体脂肪细胞分化过程中每隔一天更换含有吲哚-3-乙醛的诱导培养基，分化7天后(按照实施例1的方案进行处理)，在第7天提取细胞总RNA和总蛋白，通过Western blot检测CEBPα及PPARγ信号通路，PPARγ和FABP4的表达变化。
检测结果如图4所示，100μM浓度吲哚-3-乙醛处理人内脏前体脂肪细胞后，显著抑制人内脏前体脂肪细胞分化过程中CEBPα、PPARγ及FABP4蛋白表达水平。
以上所述仅是本发明的优选实施方式，应当指出：对于本技术领域的普通技术人员来说，在不脱离本发明原理的前提下，还可以做出若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。

Claims (1)

1.吲哚-3-乙醛在制备新型抗肥胖活性制剂中的应用。
CN202210900480.1A 2022-07-28 2022-07-28 吲哚-3-乙醛在制备新型抗肥胖活性制剂中的应用 Pending CN115040508A (zh)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5723115A (en) * 1991-05-02 1998-03-03 W. Alton Jones Cell Science Center, Inc. Inhibition of adipose tissue development and obesity
WO2009144432A1 (en) * 2008-05-30 2009-12-03 Palatin Technologies, Inc. Mc4-r agonists for the treatment of obesity
CN101742907A (zh) * 2007-05-03 2010-06-16 安塞拉制药有限公司 采用分泌型磷脂酶a2（spla2）抑制剂和spla2抑制剂组合疗法治疗心血管疾病和血脂异常
US20160206595A1 (en) * 2013-08-22 2016-07-21 Universita' Degli Studi Di Perugia Indole-3-aldehyde for treating dysreactive immune disorders
CN110051824A (zh) * 2019-04-30 2019-07-26 新乡医学院 Mbl在制备预防或治疗肥胖的药物方面的应用，筛选预防或治疗肥胖的药物的方法
CN110511267A (zh) * 2019-08-22 2019-11-29 上海市同仁医院 抗肥胖多肽、组合物及其应用和用于治疗肥胖症的药物

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5723115A (en) * 1991-05-02 1998-03-03 W. Alton Jones Cell Science Center, Inc. Inhibition of adipose tissue development and obesity
CN101742907A (zh) * 2007-05-03 2010-06-16 安塞拉制药有限公司 采用分泌型磷脂酶a2（spla2）抑制剂和spla2抑制剂组合疗法治疗心血管疾病和血脂异常
WO2009144432A1 (en) * 2008-05-30 2009-12-03 Palatin Technologies, Inc. Mc4-r agonists for the treatment of obesity
US20160206595A1 (en) * 2013-08-22 2016-07-21 Universita' Degli Studi Di Perugia Indole-3-aldehyde for treating dysreactive immune disorders
CN110051824A (zh) * 2019-04-30 2019-07-26 新乡医学院 Mbl在制备预防或治疗肥胖的药物方面的应用，筛选预防或治疗肥胖的药物的方法
CN110511267A (zh) * 2019-08-22 2019-11-29 上海市同仁医院 抗肥胖多肽、组合物及其应用和用于治疗肥胖症的药物

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
RACHEL TANOS，等: "Role of the Ah Receptor in Homeostatic Control of Fatty Acid Synthesis in the Liver", TOXICOLOGICAL SCIENCES, vol. 129, no. 2, pages 372 *
ROBERT H LUSTIG，等: "Obesity I: Overview and molecular and biochemical mechanisms", BIOCHEM PHARMACOL, vol. 199, no. 1150112, pages 1 - 12 *
董晓华: "乳杆菌T3L诱导高脂膳食小鼠脂肪棕色化作用的研究", 中国优秀硕士论文全文数据库 医药卫生科技辑, no. 1, pages 065 - 333 *
钟庆玲，等: "肠道菌群和色氨酸代谢在非酒精性脂肪性肝病中的作用", 临床肝胆病杂志, vol. 38, no. 6, pages 1411 - 1415 *

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