ReferenceID 5513
Isoginkgetin, a bioactive constituent from Ginkgo Biloba, protects against obesity-induced cardiomyopathy via enhancing Nrf2/ARE signaling
Redox Biol
Obesity-induced metabolic cardiomyopathy (MC), characterized by lipotoxicity and excessive oxidative stress, emerges as the leading cause of heart failure in the obese patients. Yet, its therapy remains very limited. Her
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Record Fields
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- Reference Id
- 5513
- Evidence Id
- 22103
- Core Evidence Id
- 22103
- Source Reference Id
- 4272
- Herb2 Reference Id
- HBREF005069
- Subject Paper Key
- HBIN030767_36162256
- Pubmed Id
- 36162256
- Doi
- 10.1016/j.redox.2022.102485
- Paper Title
- Isoginkgetin, a bioactive constituent from Ginkgo Biloba, protects against obesity-induced cardiomyopathy via enhancing Nrf2/ARE signaling
- Paper Abstract
- Obesity-induced metabolic cardiomyopathy (MC), characterized by lipotoxicity and excessive oxidative stress, emerges as the leading cause of heart failure in the obese patients. Yet, its therapy remains very limited. Here, we demonstrated that isoginkgetin (IGK), a bioactive biflavonoid isolated from medicinal herb Ginkgo Biloba, protected against obesity-induced cardiac diastolic dysfunction and adverse remodeling. Transcriptomics profiling revealed that IGK activated Nrf2 signaling in the heart tissues of the obese mice. Consistent with this observation, IGK treatment increased the nuclear translocation of Nrf2, which in turn trigger the activation of its downstream target genes (e. g. HO-1 and NQO1). In addition, IGK significantly rejuvenated mitochondrial defects in obese heart tissues as evidenced by enhancing mitochondrial respiratory capacity and resisting the collapse of mitochondrial potential and oxidative stress both in vitro and in vivo. Mechanistically, IGK stabilized Nrf2 protein via inhibiting the proteasomal degradation, independent of transcription regulation. Moreover, molecular docking and dynamics simulation assessment demonstrated a good binding mode between IGK and Nrf2/Keap1. Of note, the protective effects conferred by IGK against obesity-induced mitochondrial defects and cardiac dysfunction was compromised by Nrf2 gene silencing both in vitro and in vivo, consolidating a pivotal role of Nrf2 in IGK-elicited myocardial protection against MC. Thus, the present study identifies IGK as a promising drug candidate to alleviate obesity-induced oxidative stress and cardiomyocyte damage through Nrf2 activation, highlighting the therapeutic potential of IGK in ameliorating obesity-induced cardiomyopathy.
- Journal
- Redox Biol
- Publish Year
- 2022
- Experiment Subject
- mouse; patient
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Obesity; Cardiomyopathy; Cardiac Dysfunction; Obesity-induced Metabolic Cardiomyopathy; Heart Failure; Cardiac Diastolic Dysfunction; Mitochondrial Defects; Obese; Lipotoxicity
- Paper Title Cn
- Paper Title En
- Isoginkgetin, a bioactive constituent from Ginkgo Biloba, protects against obesity-induced cardiomyopathy via enhancing Nrf2/ARE signaling
- Bilingual Status
- semi_complete