ReferenceID 5525
Novel preventive effect of isorhamnetin on electrical and structural remodeling in atrial fibrillation
Clin Sci (Lond)
Isorhamnetin, a natural flavonoid, has strong antioxidant and antifibrotic effects, and a regulatory effect against Ca2+-handling. Atrial remodeling due to fibrosis and abnormal intracellular Ca2+ activities contributes
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Record Fields
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- Reference Id
- 5525
- Evidence Id
- 22115
- Core Evidence Id
- 22115
- Source Reference Id
- 4285
- Herb2 Reference Id
- HBREF005082
- Subject Paper Key
- HBIN031114_36540030
- Pubmed Id
- 36540030
- Doi
- 10.1042/CS20220319
- Paper Title
- Novel preventive effect of isorhamnetin on electrical and structural remodeling in atrial fibrillation
- Paper Abstract
- Isorhamnetin, a natural flavonoid, has strong antioxidant and antifibrotic effects, and a regulatory effect against Ca2+-handling. Atrial remodeling due to fibrosis and abnormal intracellular Ca2+ activities contributes to initiation and persistence of atrial fibrillation (AF). The present study investigated the effect of isorhamnetin on angiotensin II (AngII)-induced AF in mice. Wild-type male mice (C57BL/6J, 8 weeks old) were assigned to three groups: (1) control group, (2) AngII-treated group, and (3) AngII- and isorhamnetin-treated group. AngII (1000 ng/kg/min) and isorhamnetin (5 mg/kg) were administered continuously via an implantable osmotic pump for two weeks and intraperitoneally one week before initiating AngII administration, respectively. AF induction and electrophysiological studies, Ca2+ imaging with isolated atrial myocytes and HL-1 cells, and action potential duration (APD) measurements using atrial tissue and HL-1 cells were performed. AF-related molecule expression was assessed and histopathological examination was performed. Isorhamnetin decreased AF inducibility compared with the AngII group and restored AngII-induced atrial effective refractory period prolongation. Isorhamnetin eliminated abnormal diastolic intracellular Ca2+ activities induced by AngII. Isorhamnetin also abrogated AngII-induced APD prolongation and abnormal Ca2+ loading in HL-1 cells. Furthermore, isorhamnetin strongly attenuated AngII-induced left atrial enlargement and atrial fibrosis. AngII-induced elevated expression of AF-associated molecules, such as ox-CaMKII, p-RyR2, p-JNK, p-ERK, and TRPC3/6, was improved by isorhamnetin treatment. The findings of the present study suggest that isorhamnetin prevents AngII-induced AF vulnerability and arrhythmogenic atrial remodeling, highlighting its therapeutic potential as an anti-arrhythmogenic pharmaceutical or dietary supplement.
- Journal
- Clin Sci (Lond)
- Publish Year
- 2022
- Experiment Subject
- mouse; hl-1 cells
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Atrial Fibrillation; Atrial Fibrosis; Left Atrial Enlargement; Fibrosis
- Paper Title Cn
- Paper Title En
- Novel preventive effect of isorhamnetin on electrical and structural remodeling in atrial fibrillation
- Bilingual Status
- semi_complete