{"title":"Integrative multi-Omics and network pharmacology reveal angiogenesis promotion by Quan-Du-Zhong Capsule via VEGFA/PI3K-Akt pathway.","authors":"Xiaofeng Li, Wanyue Yang, Chunlan Dai, Ziyang Qiu, Xin Luan, Xuemei Zhang, Lijun Zhang","doi":"10.1016/j.jep.2024.119222","DOIUrl":null,"url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Quan-du-zhong capsule (QDZ), derived from the whole plant extract of Eucommiaulmoides Oliv., is a traditional Chinese herbal medicine used in treating vascular-related diseases, including hypertension and osteoporosis. Despite its established uses, its pro-angiogenic effects and underlying mechanisms require further investigation.</p><p><strong>Aim of this study: </strong>This study aims to investigate the pro-angiogenic effects of QDZ and explore the underlying mechanisms.</p><p><strong>Materials and methods: </strong>The chemical compositions of QDZ, including its absorbed prototypes in rats, were analyzed using UHPLC-Q Exactive-Orbitrap-MS. The pro-angiogenic activities of QDZ were evaluated in human umbilical vein endothelial cells (HUVECs) through various assays, including CCK-8, migration, scratch, tubule formation, and 3D sprouting assays. Additionally, the pro-angiogenic effects of QDZ were further assessed invivo through the matrigel plug assay and a hindlimb ischemia-reperfusion model, with three-dimensional blood flow visualized via micro-CT. A comprehensive approach involving network pharmacology, molecular docking, transcriptomics, and proteomics was utilized to explore the pro-angiogenic mechanism of QDZ, with validation by Western blot analysis.</p><p><strong>Results: </strong>QDZ significantly promoted the proliferation, migration, and tubule formation of HUVECs. The matrigel plug assay further confirmed its pro-angiogenic potential. Invivo, QDZ-treated mice displayed enhanced vascular distribution and faster blood flow recovery post-ischemia-reperfusion. Chemical analysis identified 49 compounds in QDZ, with 16 absorbed prototypes detected in rat plasma. Mechanistic investigations through network pharmacology, transcriptomics, and proteomics suggested that QDZ's pro-angiogenic effects were mediated through the VEGFA/PI3K-Akt signaling pathway, with increased phosphorylation of angiogenesis-related proteins such as PI3K, Akt, FAK, and Src.</p><p><strong>Conclusions: </strong>This study demonstrates that QDZ promotes angiogenesis via activating the VEGFA and its downstream PI3K-Akt signaling pathway, shedding light on the mechanisms that underpin its traditional medicinal use in vascular health.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119222"},"PeriodicalIF":4.8000,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of ethnopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jep.2024.119222","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Ethnopharmacological relevance: Quan-du-zhong capsule (QDZ), derived from the whole plant extract of Eucommiaulmoides Oliv., is a traditional Chinese herbal medicine used in treating vascular-related diseases, including hypertension and osteoporosis. Despite its established uses, its pro-angiogenic effects and underlying mechanisms require further investigation.
Aim of this study: This study aims to investigate the pro-angiogenic effects of QDZ and explore the underlying mechanisms.
Materials and methods: The chemical compositions of QDZ, including its absorbed prototypes in rats, were analyzed using UHPLC-Q Exactive-Orbitrap-MS. The pro-angiogenic activities of QDZ were evaluated in human umbilical vein endothelial cells (HUVECs) through various assays, including CCK-8, migration, scratch, tubule formation, and 3D sprouting assays. Additionally, the pro-angiogenic effects of QDZ were further assessed invivo through the matrigel plug assay and a hindlimb ischemia-reperfusion model, with three-dimensional blood flow visualized via micro-CT. A comprehensive approach involving network pharmacology, molecular docking, transcriptomics, and proteomics was utilized to explore the pro-angiogenic mechanism of QDZ, with validation by Western blot analysis.
Results: QDZ significantly promoted the proliferation, migration, and tubule formation of HUVECs. The matrigel plug assay further confirmed its pro-angiogenic potential. Invivo, QDZ-treated mice displayed enhanced vascular distribution and faster blood flow recovery post-ischemia-reperfusion. Chemical analysis identified 49 compounds in QDZ, with 16 absorbed prototypes detected in rat plasma. Mechanistic investigations through network pharmacology, transcriptomics, and proteomics suggested that QDZ's pro-angiogenic effects were mediated through the VEGFA/PI3K-Akt signaling pathway, with increased phosphorylation of angiogenesis-related proteins such as PI3K, Akt, FAK, and Src.
Conclusions: This study demonstrates that QDZ promotes angiogenesis via activating the VEGFA and its downstream PI3K-Akt signaling pathway, shedding light on the mechanisms that underpin its traditional medicinal use in vascular health.
期刊介绍：
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.
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