基于整合药理学平台V2.0探讨痰瘀同治方抗心肌缺血再灌注损伤的分子机制

目的:基于中医药整合药理学平台V2.0(TCMIP V2.0)探讨痰瘀同治方抗心肌缺血再灌注损伤(myocardial ischemia reperfusion injury,MIRI)的分子机制及其质量标志物.方法:利用TCMIP V2.0收集痰瘀同治方药物成分、靶标和MIRI疾病靶标,构建药物与疾病靶标互作网络,筛...

Molecular Mechanism of Tanyu Tongzhi Formula in the Treatment of Myocardial Ischemia Reperfusion Injury Based on Integrative Pharmacology-Based Research Platform of Traditional Chinese Medicine V2.0

OBJECTIVE:To investigate the molecular mechanism of Tanyu Tongzhi formula in the treatment of myocardial ischemia reperfusion injury(MIRI)based on integrative pharmacology-based research platform of traditional Chinese medicine V2.0(TCMIP V2.0).METHODS:TCMIP V2.0 was used to collect drug components,targets and MIRI disease targets of Tanyu Tongzhi formula,and drug-disease target interaction network was established.Common targets of drug and disease were screened,and biological process of the common targets was analyzed.Eventually,multidimensional network analysis of"component-target-pathway-pharmacological action"was established and the core components in the network were analyzed.RESULTS:A total of 157 pharmaceutical chemical components were collected,including pinellia ternata,red peony root,Ligusticum wallichii and licorice,and 272 corresponding targets were identified.A total of 290 targets of MIRI were obtained.Through"Traditional Chinese Medicine Association Network Mining",the first 100 targets in the core targets were analyzed,and 31 targets for drugs and diseases were found.Common targets mainly participated into the positive regulation of angiogenesis,angiogenesis,positive regulation of autophagy,inflammatory response and negative regulation of apoptosis.Kyoto Encyclopedia of Genes and Genome Encyclopedia pathway enrichment analysis showed that the common targets were mainly enriched in FoxO,HIF-1,TNF,PI3 K-Akt and VEGF signaling pathways.Further multidimensional network analysis showed that 46 components in Tanyu Tongzhi formula affected the above 5 signaling pathways by acting with 19 common targets.Quercetin,kaempferol,naringenin and baicalein participated into the occurrence and development of MIRI through 5 signaling pathways by intervention of AKT.CONCLUSIONS:Quercetin,kaempferol,naringenin and baicalein in Tanyu Tongzhi formula can inhibit MIRI by regulating inflammatory response,autophagy and apoptosis,oxidative stress and angiogenesis.