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基于潜在靶点介导的药食同源山药衍生薯蓣皂苷元对脑缺血再灌注的预防作用

Prevention properties on cerebral ischemia reperfusion of medicine food homologous Dioscorea yam-derived diosgenin based on mediation of potential targets.

作者信息

Zhang Xinxin, Wang Xingbin, Xue Zhaowei, Zhan Guanqun, Ito Yoichiro, Guo Zengjun

机构信息

College of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China; Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, Qinghai, China.

College of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China.

出版信息

Food Chem. 2021 May 30;345:128672. doi: 10.1016/j.foodchem.2020.128672. Epub 2020 Nov 19.

Abstract

I/R (cerebral ischemia reperfusion injury) is the secondary complication of ischemic stroke patients that are immediately treated with drug thrombolysis or vascular recanalization in clinic. Diosgenin (DIO) purified from medicine food homologous (MFH) Dioscorea yam source is served as a fatal starting material to synthesize multifarious steroidal anti-inflammatory drugs in medicinal field, and has previously been demonstrated the potential prevention of I/R. However, the detailed mechanisms of neuroprotective effects against I/R remain elusively understood. Here, a global proteomic dynamics of rat right hemisphere brains was executed to investigate the protein expression patterns with a quantitative LC-MS. In total, 5043 proteins were identified and 418 ones were determined to be significantly dysregulated DEPs (differentially expressed proteins) in comparison of Sham verse I/R and I/R verse DIO after onset stage of I/R, among which 5 DEPs namely BICD2, HNRNPK, CEP41, PPM1K, and ARL2BP, whose biological functions were mainly clustered into the mediation of nervous system, were selected for further validation in vitro and in vivo, and the change tendency expectedly supported the proteomic findings. Additionally, the AUC value of the combined ROC of these 5 DEPs was 0.988 with P < 0.0001, higher than every single one. Collectively, these scientific findings attributed to a typical investigation of dietary Dioscorea-enriched diosgenin in MFH research, suggesting that diosgenin or its derivatives were potential to be developed into food supplements or healthy food products to reveal healthy benefits in natural prevention and reduction risk of I/R. This work also promoted reasonable consumption of Dioscorea yams and contributed to the function of diosgenin-derived products and their applications in food industry.

摘要

脑缺血再灌注损伤(I/R)是临床中接受药物溶栓或血管再通治疗的缺血性中风患者的继发性并发症。从药食同源的山药中提纯的薯蓣皂苷元(DIO)是医药领域合成多种甾体抗炎药的重要起始原料,此前已证明其对I/R具有潜在的预防作用。然而,其对I/R神经保护作用的详细机制仍不清楚。在此,通过定量液相色谱-质谱联用技术对大鼠右半球脑进行了整体蛋白质组动力学研究,以探究蛋白质表达模式。总共鉴定出5043种蛋白质,在I/R发病阶段后,与假手术组对比I/R组以及I/R组对比DIO组中,有418种被确定为显著失调的差异表达蛋白(DEP),其中5种DEP,即BICD2、HNRNPK、CEP41、PPM1K和ARL2BP,其生物学功能主要集中在神经系统的介导方面,被选择在体外和体内进行进一步验证,其变化趋势符合蛋白质组学研究结果。此外,这5种DEP联合ROC的AUC值为0.988,P<0.0001,高于单个DEP。总的来说,这些科学发现归因于对药食同源研究中富含薯蓣的薯蓣皂苷元的典型研究,表明薯蓣皂苷元或其衍生物有潜力开发成食品补充剂或健康食品,以在自然预防和降低I/R风险方面显示健康益处。这项工作还促进了山药的合理消费,并有助于薯蓣皂苷元衍生产品的功能及其在食品工业中的应用。

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