ArticlePloS one2016
Coordinated Activation of VEGF/VEGFR-2 and PPARδ Pathways by a Multi-Component Chinese Medicine DHI Accelerated Recovery from Peripheral Arterial Disease in Type 2 Diabetic Mice.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 14 citations in OpenAlex.
- Effects of Danhong Injection () on Peri-Procedural Myocardial Injury and Microcirculatory Resistance in Patients with Unstable Angina Undergoing Elective Percutaneous Coronary Intervention: A Pilot Randomized Study.Chinese journal of integrative medicine · 2021Trial
- Chinese Herbal Medicines for Diabetic Cardio-Cerebrovascular Diseases: Key Bioactive Metabolites and Action Mechanisms.Journal of nutrition and metabolism · 2026Review
- Integrated metabolomics and transcriptomics analysis reveals the mechanism of Tangbi capsule for diabetic lower extremities arterial disease.Frontiers in microbiology · 2024Article
- Challenges and Perspectives in Target Identification and Mechanism Illustration for Chinese Medicine.Chinese journal of integrative medicine · 2023Review
- Differential action of pro-angiogenic and anti-angiogenic components of Danhong injection in ischemic vascular disease or tumor models.Chinese medicine · 2022Article
- Downregulation of miRNA‑328 promotes the angiogenesis of HUVECs by regulating the PIM1 and AKT/mTOR signaling pathway under high glucose and low serum condition.Molecular medicine reports · 2020Article
- A Defined Combination of Four Active Principles From the Danhong Injection Is Necessary and Sufficient to Accelerate EPC-Mediated Vascular Repair and Local Angiogenesis.Frontiers in pharmacology · 2019Article
- Acute and chronic effects of exercise on mRNA expression in the skeletal muscle of two mouse models of peripheral artery disease.PloS one · 2017Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetic mellitus (DM) patients are at an increased risk of developing peripheral arterial disease (PAD). Danhong injection (DHI) is a Chinese patent medicine widely used for several cardiovascular indications but the mechanism of action is not well-understood. We investigated the therapeutic potential of DHI on experimental PAD in mice with chemically induced as well as genetic (KKAy) type 2 DM and the overlapping signaling pathways regulating both therapeutic angiogenesis and glucose homeostasis. Compared with normal genetic background wild type (WT) mice, both DM mice showed impaired perfusion recovery in hind-limb ischemia (HLI) model. DHI treatment significantly accelerated perfusion recovery, lowered blood glucose and improved glucose tolerance in both DM models. Bioluminescent imaging demonstrated a continuous ischemia-induced vascular endothelial growth factor receptor 2 (VEGFR-2) gene expressions with a peak time coincident with the maximal DHI stimulation. Flow cytometry analysis showed a DHI-mediated increase in endothelial progenitor cell (EPC) mobilization from bone marrow to circulating peripheral blood. DHI administration upregulated the expression of vascular endothelial growth factor A (VEGF-A) and VEGF receptor-2 (VEGFR-2) in ischemic muscle. A cross talk between ischemia-induced angiogenesis and glucose tolerance pathways was analyzed by Ingenuity Pathway Analysis (IPA) which suggested an interaction of VEGF-A/VEGFR-2 and peroxisome proliferator-activated receptor δ (PPARδ)/peroxisome proliferator-activated receptor γ (PPARγ) genes. We confirmed that upregulation of VEGF-A/VEGFR-2 by DHI promoted PPARδ gene expression in both type 2 diabetic mice. Our findings demonstrated that a multi-component Chinese medicine DHI effectively increased blood flow recovery after tissue ischemia in diabetic mice by promoting angiogenesis and improving glucose tolerance through a concomitant activation of VEGF-A/VEGFR-2 and PPARδ signaling pathways.
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