Andrographolide protects against atrial fibrillation by alleviating oxidative stress injury and promoting impaired mitochondrial bioenergetics / 浙江大学学报(英文版)(B辑:生物医学和生物技术)
Journal of Zhejiang University. Science. B
; (12): 632-649, 2023.
Artículo
en Inglés
| WPRIM (Pacífico Occidental)
| ID: wpr-982404
Biblioteca responsable:
WPRO
ABSTRACT
Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia seen in clinical settings, which has been associated with substantial rates of mortality and morbidity. However, clinically available drugs have limited efficacy and adverse effects. We aimed to investigate the mechanisms of action of andrographolide (Andr) with respect to AF. We used network pharmacology approaches to investigate the possible therapeutic effect of Andr. To define the role of Andr in AF, HL-1 cells were pro-treated with Andr for 1 h before rapid electronic stimulation (RES) and rabbits were pro-treated for 1 d before rapid atrial pacing (RAP). Apoptosis, myofibril degradation, oxidative stress, and inflammation were determined. RNA sequencing (RNA-seq) was performed to investigate the relevant mechanism. Andr treatment attenuated RAP-induced atrial electrophysiological changes, inflammation, oxidative damage, and apoptosis both in vivo and in vitro. RNA-seq indicated that oxidative phosphorylation played an important role. Transmission electron microscopy and adenosine triphosphate (ATP) content assay respectively validated the morphological and functional changes in mitochondria. The translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus and the molecular docking suggested that Andr might exert a therapeutic effect by influencing the Keap1-Nrf2 complex. In conclusions, this study revealed that Andr is a potential preventive therapeutic drug toward AF via activating the translocation of Nrf2 to the nucleus and the upregulation of heme oxygenase-1 (HO-1) to promote mitochondrial bioenergetics.
Texto completo:
Disponible
Contexto en salud:
ODS3 - Meta 3.4 Reducir las muertes prematuras por enfermedades no transmisibles
Problema de salud:
Enfermedad Cardiovascular
Base de datos:
WPRIM (Pacífico Occidental)
Asunto principal:
Fibrilación Atrial
/
Transducción de Señal
/
Estrés Oxidativo
/
Metabolismo Energético
/
Hemo-Oxigenasa 1
/
Factor 2 Relacionado con NF-E2
/
Simulación del Acoplamiento Molecular
/
Proteína 1 Asociada A ECH Tipo Kelch
/
Inflamación
/
Mitocondrias
Límite:
Animales
Idioma:
Inglés
Revista:
Journal of Zhejiang University. Science. B
Año:
2023
Tipo del documento:
Artículo