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郭铃,刘静,郭渠莲,靳艳玲,刘文君.紫薯花青素的成分鉴定及其抗白血病潜在靶点的筛选验证[J].广西科学,2022,29(5):949-958. [点击复制]
- GUO Ling,LIU Jing,GUO Qulian,JIN Yanling,LIU Wenjun.Component Identification of Purple Sweet Potato Anthocyanins and Screening and Verification of Their Potential Targets against Leukemia[J].Guangxi Sciences,2022,29(5):949-958. [点击复制]
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| 紫薯花青素的成分鉴定及其抗白血病潜在靶点的筛选验证 |
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郭铃1, 刘静1, 郭渠莲1, 靳艳玲2, 刘文君1
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| (1.西南医科大学附属医院儿科, 儿童血液肿瘤与出生缺陷实验室, 四川省出生缺陷临床医学研究中心, 四川泸州 646000;2.中国科学院成都生物研究所, 中国科学院环境与应用微生物重点实验室, 四川省环境微生物重点实验室, 四川成都 610041) |
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| 摘要: |
| 为探讨紫薯花青素(Purple Sweet Potato Anthocyanin,PSPA)在急性淋巴细胞白血病(Acute Lymphoblastic Leukemia，ALL)防治中的靶点，本文提取、纯化并鉴定了紫薯花青素，基于分子对接技术预测了紫薯花青素的潜在靶点。结果显示：从川紫4号紫薯中鉴定出25种花青素，分别是矢车菊素、芍药色素、天竺葵色素及其衍生物，各种成分的相对含量为0.1%-23.0%。其中，矢车菊素3-阿魏酸-对羟基苯甲酰槐糖苷-5-葡萄糖苷(Cyanidin 3-feruloyl-p-hydroxybenzoyl sophoroside-5-glucoside)相对含量最高，达到22.63%。基于矢车菊素抗氧化活性较其他两种花青素更强、二乙酰化的花青素更稳定的特点，该化合物被选择作为后续分子对接的配体，分别与程序性细胞死亡(Programmed Cell Death,PCD)，如凋亡、焦亡、坏死性凋亡、铁死亡及铜死亡相关的关键蛋白进行分子对接分析。结果表明，紫薯花青素可以结合到抗凋亡蛋白(Bcl-2)、E3泛素连接酶(Parkin)蛋白、胱氨酸转运蛋白(SLC7A11)、铁氧还蛋白1(FDX1)以及c-Myc蛋白上，从而影响蛋白分子的结构和活性。转录组和Western blot结果进一步验证紫薯花青素可以抑制Bcl-2、Parkin、SLC7A11、FDX1以及c-Myc蛋白的表达，最终诱导细胞发生一定程度的程序性死亡。本研究通过分子对接分析初步获得了紫薯花青素的潜在靶点，为后续生理生化实验提供了理论依据，也为白血病的临床治疗拓展了新的思路。 |
| 关键词: 白血病 紫薯花青素 分子对接 程序性细胞死亡 铜死亡 |
| DOI：10.13656/j.cnki.gxkx.20220809.001 |
| 投稿时间：2022-04-13修订日期：2022-06-27 |
| 基金项目:四川省自然科学基金(2022NSFSC0723)，四川省卫生健康委员会医学科技项目(21PJ091)，四川省中医药管理局科学技术研究专项(2020JC0135)，泸州市人民政府-西南医科大学科技战略合作项目应用基础研究专项(2021LZXNYD-J22)，西南医科大学自然科学应用基础研究项目青年项目(2021ZKQN083，2020ZRQNB029)，西南医科大学附属医院博士启动基金，四川省科技计划项目(22ZDYF3802),财政部和农业农村部：国家现代农业产业技术体系资助项目(CARS-10-B22)资助。 |
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| Component Identification of Purple Sweet Potato Anthocyanins and Screening and Verification of Their Potential Targets against Leukemia |
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GUO Ling1, LIU Jing1, GUO Qulian1, JIN Yanling2, LIU Wenjun1
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| (1.Department of Pediatrics, Children Hematological Oncology and Birth Defects Laboratory, The Affiliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for Birth Defects, Luzhou, Sichuan, 646000, China;2.CAS Key Laboratory of Environmental and Applied Microbiology, Environmental Microbiology Key Laboratory of Sichuan Province, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, Sichuan, 610041, China) |
| Abstract: |
| In order to explore the targets of Purple Sweet Potato Anthocyanin (PSPA) in the prevention and treatment of Acute Lymphoblastic Leukemia (ALL),PSPA was extracted,purified and identified in this article.The potential targets of PSPA were predicted based on molecular docking technology.And 25 kinds of anthocyanins were identified from Chuanzi No.4 purple sweet potato,including cyanidin,peoniflorin,pelargonidin and their derivatives.The relative content of each ingredient was between 0.1% and 23.0%.Among them,the relative content of Cyanidin 3-feruloyl-p-hydroxybenzoyl-sophoroside-5-glucoside was the highest,reaching 22.63%.Based on the stronger antioxidant activity of cyanidin than the other two anthocyanins and the more stable characteristics of diacetylated anthocyanins,the compound was selected as a ligand for subsequent molecular docking,and molecular docking analysis was performed with key proteins related to Programmed Cell Death (PCD),such as apoptosis,pyroptosis,necroptosis,ferroptosis and cuprotosis.The results showed that PSPA could bind with anti-apoptotic protein (Bcl-2),E3 ubiquitin ligase (Parkin protein),cystine transporter (SLC7A11),ferredoxin 1 (FDX1) and c-Myc protein,thereby affecting the structure and activity of protein molecules.The results of transcriptome and western blot further verified that PSPA could inhibit the expression of Bcl-2,Parkin,SLC7A11,FDX1 and c-Myc proteins,and finally induce a certain degree of programmed cell death.In this study,the potential targets of PSPA were preliminarily obtained by molecular docking analysis,which provided a theoretical basis for subsequent physiological and biochemical experiments,and also expanded new ideas for clinical treatment of leukemia. |
| Key words: leukemia purple sweet potato anthocyanins molecular docking programmed cell death cuprotosis |
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