ArticleAngiogenesis2011
Ginsenoside-Rg1 mediates a hypoxia-independent upregulation of hypoxia-inducible factor-1α to promote angiogenesis.
Article in Angiogenesis, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 67 citations in OpenAlex.
- Yin and Yang of ginsenosides: Molecular mechanisms of bidirectional regulation of angiogenesis.Journal of ginseng research · 2026Review
- A Contemporary Review of Myocardial Infarction with Emphasis on Clinical Trials and Therapeutic Approaches.Current hypertension reviews · 2026Review
- Roles and mechanisms of ginsenoside Rg1 in coronary artery disease: Progress and perspectives.Journal of ginseng research · 2025Review
- Hypoxic niches established via endogenous oxygen production in scaffold under anoxia for enhanced bone regeneration.Regenerative biomaterials · 2025Article
- Panax notoginseng saponins promotes angiogenesis after cerebral ischemia-reperfusion injury.Journal of ginseng research · 2024Article
- Multiple roles for hypoxia inducible factor 1-alpha in airway epithelial cells during mucormycosis.Nature communications · 2024Article
- Bone transport induces the release of factors with multi-tissue regenerative potential for diabetic wound healing in rats and patients.Cell reports. Medicine · 2024Article
- Analysis of the Effects of Ninjin'yoeito on Physical Frailty in Mice.International journal of molecular sciences · 2022Article
- Chinese Herbal Medicine Adjusting Brain Microenvironment via Mediating Central Nervous System Lymphatic Drainage in Alzheimer's Disease.Chinese journal of integrative medicine · 2022Review
- Natural Herbal Medicine as a Treatment Strategy for Myocardial Infarction through the Regulation of Angiogenesis.Evidence-based complementary and alternative medicine : eCAM · 2022Review
- Ginsenoside Rg1 Nanoparticles Induce Demethylation of H3K27me3 in VEGF-A and Jagged 1 Promoter Regions to Activate Angiogenesis After Ischemic Stroke.International journal of nanomedicine · 2022Article
- Mechanisms and Efficacy of Traditional Chinese Medicine in Heart Failure.Frontiers in pharmacology · 2022Review
- Bioactive strontium ions/ginsenoside Rg1-incorporated biodegradable silk fibroin-gelatin scaffold promoted challenging osteoporotic bone regeneration.Materials today. Bio · 2021Article
- Traditional Chinese Medicine ShenZhuGuanXin Granules Mitigate Cardiac Dysfunction and Promote Myocardium Angiogenesis in Myocardial Infarction Rats by Upregulating PECAM-1/CD31 and VEGF Expression.Evidence-based complementary and alternative medicine : eCAM · 2017Article
- Prevention of AMI Induced Ventricular Remodeling: Inhibitory Effects of Heart-Protecting Musk Pill on IL-6 and TNF-Alpha.Evidence-based complementary and alternative medicine : eCAM · 2017Article
- Total saponins of panaxnotoginseng promotes lymphangiogenesis by activation VEGF-C expression of lymphatic endothelial cells.Journal of ethnopharmacology · 2016Article
- Angiogenesis in Ischemic Stroke and Angiogenic Effects of Chinese Herbal Medicine.Journal of clinical medicine · 2016Review
- Ginsenoside Rg1 protects starving H9c2 cells by dissociation of Bcl-2-Beclin1 complex.BMC complementary and alternative medicine · 2016Article
- Rolipram stimulates angiogenesis and attenuates neuronal apoptosis through the cAMP/cAMP-responsive element binding protein pathway following ischemic stroke in rats.Experimental and therapeutic medicine · 2016Article
- Molecular mechanisms governing different pharmacokinetics of ginsenosides and potential for ginsenoside-perpetrated herb-drug interactions on OATP1B3.British journal of pharmacology · 2015Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia-inducible factor (HIF-1) is the key transcription regulator for multiple angiogenic factors and is an appealing target. Ginsenoside-Rg1, a nontoxic saponin isolated from the rhizome of Panax ginseng, exhibits potent proangiogenic activity and has the potential to be developed as a new angiotherapeutic agent. However, the mechanisms by which Rg1 promotes angiogenesis are not fully understood. Here, we show that Rg1 is an effective stimulator of HIF-1α under normal cellular oxygen conditions in human umbilical vein endothelial cells. HIF-1α steady-state mRNA was not affected by Rg1. Rather, HIF-1α protein synthesis was stimulated by Rg1. This effect was associated with constitutive activation of phosphatidylinositol 3-kinase (PI3K)/Akt and its effector p70 S6 kinase (p70(S6K)), but not extracellular-signal regulated kinase 1/2. We further revealed that HIF-1α induction triggered the expression of target genes, including vascular endothelial growth factor (VEGF). The use of small molecule inhibitors LY294002 or rapamycin to inhibit PI3K/Akt and p70(S6K) activities, respectively, resulted in diminished HIF-1α activation and subsequent VEGF expression. RNA interference-mediated knockdown of HIF-1α suppressed Rg1-induced VEGF synthesis and angiogenic tube formation, confirming that the effect was HIF-1α specific. Similarly, the angiogenic phenotype could be reversed by inhibition of PI3K/Akt and p70(S6K). These results define a hypoxia-independent activation of HIF-1α, uncovering a novel mechanism for Rg1 that could play a major role in angiogenesis and vascular remodeling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.