Oroxin B Resembles Bisoprolol in Attenuating Beta1‐Adrenergic Receptor Autoantibody‐Induced Atrial Remodelling via the PTEN/AKT/mTOR Signalling Pathway

ABSTRACT Beta1‐adrenergic receptor autoantibodies (β1‐AAbs) promote atrial remodelling and ultimately lead to the development of atrial fibrillation (AF). Oroxin B is a natural flavonoid glycoside with a variety of biological activities, including anti‐inflammatory and autophagy‐promoting effects, and has therapeutic benefits for a variety of diseases. The aim of this study was to investigate the potential therapeutic role of Oroxin B in the development of β1‐AAb‐induced atrial fibrillation and to elucidate the underlying mechanisms involved. We established a rat model of β1‐AAb‐induced atrial fibrillation via active immunisation. The first stage was divided into three groups: the control group, the β1‐AAb group and the β1‐AAb + bisoprolol group. The second stage was divided into three groups: the control group, the β1‐AAb group and the β1‐AAb + Oroxin B group. Serum levels of β1‐AAbs, atrial tissue levels of cyclic monophosphate (cAMP), atrial electrophysiological parameters, cardiac structure and function, mitochondrial structure, autophagy levels, cardiomyocyte apoptosis and myocardial fibrosis were examined. The results showed that bisoprolol, a β1‐blocker, improved β1‐AAb‐induced atrial electrical remodelling, reduced atrial collagen deposition, ameliorated the increase in LAD and regulated the balance of autophagy and apoptosis in atrial myocytes through the PTEN/AKT/mTOR signalling pathway. Oroxin B, a PTEN agonist, can improve the impairment of autophagy homeostasis and apoptosis in atrial tissue by activating the PTEN/AKT/mTOR signalling pathway, thereby improving atrial structure and electrical remodelling. Moreover, Oroxin B may play a therapeutic role in β1AAb‐induced atrial fibrillation. In conclusion, our results demonstrate the potential therapeutic role of Oroxin B in β1AAb‐induced atrial fibrillation and the underlying mechanisms, suggesting that Oroxin B may be an effective antiarrhythmic medication.