基于网络药理学及实验验证探讨当归多糖改善高原低氧认知障碍的作用机制  

Mechanism of Angelica polysaccharide in improving highaltitude hypoxia-induced cognitive impairment based on network pharmacology and experimental validation

作　　者：刘菲菲 陈丽萍 钟艳 常熙雯 王延玲 李豆豆 仇芳芳 王荣 LIU Feifei;CHEN Liping;ZHONG Yan;CHANG Xiwen;WANG Yaning;LI Doudou;QIU Fangfang;WANG Rong(Department of Pharmacy,940th Hospital,PLA Joint Logistic Support Force,Lanzhou 730050;Gansu University of Chinese Medicine,Lanzhou 730000)

机构地区：[1]中国人民解放军联勤保障部队第九四〇医院药剂科,兰州730050 [2]甘肃中医药大学,兰州730000

出　　处：《中国食品添加剂》2024年第12期104-113,共10页China Food Additives

基　　金：甘肃省科技计划资助项目(编号:23ZDFA013-5);兰州市科技局项目(编号:2023-2-62);第九四〇医院院内课题(编号:2021yxky043,2021yxky082)。

摘　　要：基于网络药理学及实验验证探讨当归多糖改善高原低氧认知障碍的作用机制。借助Similarity ensemble approach(SEA)等数据库预测当归多糖各单糖的靶点,利用GeneCards等数据库获取高原低氧认知障碍的靶点,取两者靶点的交集,绘制交集靶点PPI网络图,并进行GO和KEGG富集分析。结果筛选得到当归多糖靶点303个,高原低氧认知障碍靶点783个,交集靶点共29个。富集分析表明,当归多糖可能通过调控PI3K/Akt、JAK-STAT、HIF-1等信号通路发挥作用。进行小鼠Morris水迷宫实验,结果表明当归多糖能缩短小鼠的潜伏期,增加穿越平台次数,并能降低小鼠海马和皮层组织中MDA和AchE含量,升高SOD水平,降低炎症因子水平,当归多糖还能上调小鼠海马和皮层组织中PI3K、P-Akt、Akt、Bcl-2并下调Bax蛋白表达,改善海马组织病理损伤。因此当归多糖可改善高原低氧认知障碍,可能与抗氧化、抗炎,调控PI3KAkt信号通路有关。To explore the mechanism of Angelica polysaccharide in improving cognitive impairment caused by hypoxia at high altitudes through network pharmacology and experimental validation.Similarity ensemble approach(SEA)was used to predict the target of each monosaccharide of Angelica polysaccharide and obtained the target related to cognitive impairment caused by hypoxia at high altitudes using GeneCards and other databases.The intersection of these targets was analyzed,leading to the construction of a Protein-Protein Interaction(PPI)network and subsequent Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.A total of 303 targets for Angelica polysaccharides and 783 targets for hypoxia-induced cognitive impairment were identified,with 29 common targets.Enrichment analysis indicated that Angelica polysaccharides might exert their effects by modulating signaling pathways such as PI3K/Akt,JAK-STAT,and HIF-1.In a Morris water maze experiment with mice,results showed that Angelica polysaccharides shortened the latency period,increased the number of platform crossings,and reduced the levels of malondialdehyde(MDA)and acetylcholinesterase(AchE)in mice hippocampal and cortical tissues,while increasing superoxide dismutase(SOD)levels and decreasing inflammatory factor levels.Additionally,Angelica polysaccharides upregulated the expression of PI3K,P-Akt,Akt,and Bcl-2 and downregulated Bax protein expression in the hippocampus and cortex of mice,improving pathological damage in the hippocampal tissue of mice.Angelica polysaccharide could improve the cognitive impairment caused by hypoxia at high altitudes,likely associated with their antioxidant,anti-inflammatory and regulation of PI3K-Akt signaling pathway.

关 键 词：网络药理学 当归多糖 高原低氧认知障碍 PI3K-AKT信号通路 

分 类 号：TS201[轻工技术与工程—食品科学]