ArticleFrontiers in endocrinology2018
Phloretin Prevents Diabetic Cardiomyopathy by Dissociating Keap1/Nrf2 Complex and Inhibiting Oxidative Stress.
Article in Frontiers in endocrinology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 62 citations in OpenAlex.
- Effects of Diet Strategy and Nutrients on the Progression and Prevention of Diabetic Cardiomyopathy: A Narrative Review.Food science & nutrition · 2026Review
- The clinical evaluation value of the NRF2-mediated antioxidant stress mechanism in elderly patients with type 2 diabetes mellitus complicated by osteoporosis.Journal of medical biochemistry · 2026Article
- Phloretin inhibits ferroptosis by restoring the antioxidant capacity of bovine adipose and muscle cells via the AMPK-PPAR signaling pathway.Stress biology · 2025Article
- A comprehensive review on diabetic cardiomyopathy (DCM): histological spectrum, diagnosis, pathogenesis, and management with conventional treatments and natural compounds.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- The role of Nrf2 signaling pathway in diabetic cardiomyopathy: from pathogenesis to traditional Chinese medicine interventions.Frontiers in cardiovascular medicine · 2025Review
- Review
- A Review on the Natural Products in Treatment of Diabetic Cardiomyopathy (DCM).Reviews in cardiovascular medicine · 2024Review
- Phloretamide Protects against Diabetic Kidney Damage and Dysfunction in Diabetic Rats by Attenuating Hyperglycemia and Hyperlipidemia, Suppressing NF-κβ, and Upregulating Nrf2.Pharmaceutics · 2024Article
- Small molecule deoxynyboquinone triggers alkylation and ubiquitination of Keap1 at Cys489 on Kelch domain for Nrf2 activation and inflammatory therapy.Journal of pharmaceutical analysis · 2024Article
- Chronic intermittent hypoxia aggravated diabetic cardiomyopathy through LKB1/AMPK/Nrf2 signaling pathway.PloS one · 2024Article
- Phloretin targets SIRT1 to alleviate oxidative stress, apoptosis, and inflammation in deep venous thrombosis.Toxicological research · 2024Article
- AR/PCC herb pair inhibits osteoblast pyroptosis to alleviate diabetes-related osteoporosis by activating Nrf2/Keap1 pathway.Journal of cellular and molecular medicine · 2023Article
- Esculeoside A Decreases Diabetic Cardiomyopathy in Streptozotocin-Treated Rats by Attenuating Oxidative Stress, Inflammation, Fibrosis, and Apoptosis: Impressive Role of Nrf2.Medicina (Kaunas, Lithuania) · 2023Article
- Review
- Phytochemical activators of Nrf2: a review of therapeutic strategies in diabetes.Acta biochimica et biophysica Sinica · 2022Review
- Design, synthesis and evaluation of novel small molecules acting as Keap1-Nrf2 protein-protein interaction inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2022Article
- [Fucoxanthin regulates Nrf2/Keap1 signaling to alleviate myocardial hypertrophy in diabetic rats].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- Phenols and terpenoids: natural products as inhibitors of NLRP3 inflammasome in cardiovascular diseases.Inflammopharmacology · 2022Review
- The Beneficial Effects of Chinese Herbal Monomers on Ameliorating Diabetic Cardiomyopathy via Nrf2 Signaling.Oxidative medicine and cellular longevity · 2022Review
- Transcriptome and proteome profiling of activated cardiac fibroblasts supports target prioritization in cardiac fibrosis.Frontiers in cardiovascular medicine · 2022Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
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Abstract
Hyperglycemia induces chronic inflammation and oxidative stress in cardiomyocyte, which are the main pathological changes of diabetic cardiomyopathy (DCM). Treatment aimed at these processes may be beneficial in DCM. Phloretin (PHL), a promising natural product, has many pharmacological activities, such as anti-inflammatory, anticancer, and anti-oxidative function. The aim of this study was to investigate whether PHL could ameliorate the high glucose-mediated oxidation, hypertrophy, and fibrosis in H9c2 cells and attenuate the inflammation- and oxidation-mediated cardiac injury. In this study, PHL induced significantly inhibitory effect on the expression of pro-inflammatory, hypertrophy, pro-oxidant, and fibrosis cytokines in high glucose-stimulated cardiac H9c2 cells. Furthermore, PHL decreased the levels of serum lactate dehydrogenase, aspartate aminotransferase, and creatine kinase-MB, and attenuated the progress in the fibrosis, oxidative stress, and pathological parameters via Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor E2-related factor 2 (Nrf2) pathway in diabetic mice. In additional, molecular modeling and immunoblotting results confirmed that PHL might obstruct the interaction between Nrf2 and Keap1 through direct binding Keap1, and promoting Nrf2 expression. These results provided evidence that PHL could suppress high glucose-induced cardiomyocyte oxidation and fibrosis injury, and that targeting Keap1/Nrf2 may provide a novel therapeutic strategy for human DCM in the future.
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