目的 探究红景天口服液的活性成分及其抗急性高原反应的机制。方法 采用超高效液相色谱-四级杆飞行时间串联质谱(ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry，UPLC-Q-TOF/MS)法表征红景天口服液的主要化学成分。运用网络药理学方法检索红景天口服液和急性高原反应(acute mountain sickness，AMS)的潜在靶点，将药物靶点与AMS相关靶点取交集，基于STRING 数据库进行靶点蛋白相互作用网络(protein-protein interac-tion，PPI)分析，借助DAVID数据库平台进行基因本体(gene ontology，GO)功能分析及京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes，KEGG)通路富集分析。考察红景天苷、红景天素、对羟基苯甲醇、酪醇 4 个活性成分对糖氧剥夺诱导嗜铬细胞瘤 12(pheochromocytoma 12，PC12)细胞损伤模型的存活率及乳酸脱氢酶(lactate dehydrogenase，LDH)露出率的影响。结果 从红景天口服液中鉴定了40 个主要的化学成分，进一步筛选出抗AMS活性成分14 个，所对应相关靶点34 个，其中肿瘤坏死因子(tumor necrosis factor，TNF)、白介素 6(interleukin 6，IL-6)、血管内皮生长因子A(vascular endothelial growth factor A，VEGFA)、环加氧酶 2(prostaglandin-endoper-oxide synthase 2，PTGS2)等靶点的关联性较强;红景天口服液治疗AMS主要涉及磷脂酰肌醇3-激酶-蛋白激酶B(phosphatidylinositol 3-kinase-protein kinase B，PI3K-Akt)、缺氧诱导因子1(hypoxi-a-inducible factor 1，HIF-1)和丝裂原活化蛋白激酶(mitogen-activated protein kinase，MAPK)等信号通路。红景天苷、红景天素、对羟基苯甲醇、酪醇可显著提高糖氧剥夺PC12 细胞损伤模型的存活率及减少其LDH露出率。结论 红景天口服液中的红景天苷、酪醇、红景天素、对羟基苯甲醇等可能是抗急性高原反应的潜在药效物质基础，作用机制可能与HIF-1、MAPK、PI3K-Akt等信号通路有关。
Exploring the active components and mechanism of anti-acute mountain sickness of Hongjingtian Oral Liquid based on UPLC-Q-TOF/MS and network pharmacology
Objective To explore the active ingredients of Hongjingtian Oral Liquid and the mechanism against acute mountain sickness.Methods Ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF/MS)was applied to profile the main chemical constituents of Hongjingtian Oral Liquid.Potential targets of Hongjingtian Oral Liquid and Acute mountain sickness(AMS)were retrieved by network pharmacological methods,drug targets were intersected with AMS-related targets.The target protein-protein interaction network(PPI)was analyzed based on the STRING database.With the help of DAVID database,the gene ontology(GO)function analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed.The effects of salidroside,rhodiosin,p-hydroxybenzyl alcohol and tyrosol on the survival rate and lactate dehydrogenase(LDH)exposure rate of Pheochromocytoma 12(PC12)cell injury model induced by glucose and oxygen deprivation were investigated.Results Forty main chemical components were identified from Hongjingtian Oral Liquid,and 14 anti-AMS active components were screened,and 34 related targets were identified.Among them,tumor necrosis factor(TNF),interleukin-6(IL-6),vascular endothelial growth factor A(VEGFA)and prostaglandin-endoperoxide synthase 2(PTGS2)were highly correlated.The treatment for AMS of Hongjingtian Oral Liquid mainly involves signaling pathways such as phosphatidylinositol 3-kinase-protein kinase B(PI3K-Akt),hypoxia-inducible factor 1(HIF-1)and mitogen-activated protein kinase(MAPK),etc.Salidroside,rhodiosin,p-hydroxybenzyl alcohol and tyrosol can improve the survival rate of PC12 cell injury model and reduce the exposure rate of LDH.Conclusion The salidroside,tyrosol,rhodiosin and p-hydroxybenzyl alcohol in Hongjingtian Oral Liquid may be the potential pharmacodynamic material basis,and may play an anti-AMS role by regulating HIF-1,MAPK,PI3K-Akt and other signaling pathways.
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