ReferenceID 5973
Phloretin ameliorates diabetes-induced endothelial injury through AMPK-dependent anti-EndMT pathway
Pharmacol Res
Diabetic cardiovascular complications contribute more than half of diabetes mortality. Endothelial damage and subsequent pathological changes play a key role in this process. Phloretin, a plant-derived dihydrochalcone co
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Record Fields
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- Reference Id
- 5973
- Evidence Id
- 22563
- Core Evidence Id
- 22563
- Source Reference Id
- 5210
- Herb2 Reference Id
- HBREF006007
- Subject Paper Key
- HBIN039576_35381340
- Pubmed Id
- 35381340
- Doi
- 10.1016/j.phrs.2022.106205
- Paper Title
- Phloretin ameliorates diabetes-induced endothelial injury through AMPK-dependent anti-EndMT pathway
- Paper Abstract
- Diabetic cardiovascular complications contribute more than half of diabetes mortality. Endothelial damage and subsequent pathological changes play a key role in this process. Phloretin, a plant-derived dihydrochalcone compound, was reported to have the activities in regulating metabolism homeostasis and anti-inflammation. However, its effects and the mechanism on early stage endothelial injury caused by diabetes are not clear yet. In our present study, human umbilical vein endothelial cells (HUVECs) were stimulated by high glucose or advanced glycation end products (AGEs) to induce endothelial damage, and streptozotocin (STZ) -induced diabetes mouse model was used for in vivo study. Our results showed that phloretin effectively reduced endothelial damage marker monocyte chemotactic protein-1 (MCP1) as well as pro-calcification factors bone morphogenetic protein-2 (BMP2) and receptor activator of NF-κB ligand (RANKL) expression, reversed the increased vimentin and decreased CD31 dose-dependently in vitro and in vivo. Phloretin had no effect on blood glucose level. However, it ameliorated endothelial injury and vascular fibrosis in diabetic mice. Further experiments revealed that phloretin could enhance AMP activated protein kinase (AMPK) activation and upregulate peroxidase proliferator activated receptor-gamma coactivator-lα (PGC1α) level, and inhibit the activation of TGFβ-Smad2-Snail signalling pathway which was abrogated by AMPK inhibitor, providing a rational mechanism that AMPK activation was required for the effects of phloretin on endothelial injury and endothelial-mesenchymal transformation (EndMT). Our data reveal a new role of phloretin in protection of diabetic endothelial damage via AMPK-dependent anti-EndMT activation, and also provide a potential therapeutic way for diabetic endothelial damage and its subsequent cardiovascular complications.
- Journal
- Pharmacol Res
- Publish Year
- 2022
- Experiment Subject
- mouse; human; human umbilical vein endothelial cells; huvecs
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Vascular Fibrosis; Endothelial Injury; Diabetic Endothelial Damage; Diabetic Cardiovascular Complications; Diabetic; Diabetes
- Paper Title Cn
- Paper Title En
- Phloretin ameliorates diabetes-induced endothelial injury through AMPK-dependent anti-EndMT pathway
- Bilingual Status
- semi_complete