Baicalin Prevents Chronic β‐<scp>AR</scp> Agonist‐Induced Heart Failure via Preventing Oxidative Stress and Overactivation of the <scp>NADPH</scp> Oxidase <scp>NOX2</scp>

Heart failure (HF) remains the leading cause of mortality worldwide. Although various drugs are currently used in the treatment of HF, including angiotensin receptor blockers, angiotensin-converting enzyme inhibitors and beta blockers, none of these drugs can reverse the physiological remodelling of the heart associated with HF. Therefore, discovering novel drugs that can limit the extent of HF or prevent the structural dysfunction of the heart during HF progression is urgently needed. Baicalin is a natural flavonoid widely used in Traditional Chinese Medicine for its anti-inflammatory and anti-oxidative effects; however, the role of baicalin in chronic HF, in particular its underlying mechanisms of action, remains largely unelucidated. Murine models of beta-adrenergic receptor agonist (β-AR)-induced HF were induced via chronic induction with isoproterenol (ISO) for 4 weeks. Furthermore, we examined the effects and mechanisms of baicalin in protecting against ISO-induced cardiac impairment and HF. Daily administrations of baicalin robustly protected against chronic ISO-induced pathophysiological changes of the heart, including cardiac hypertrophy, reduced ejection fraction, fibrosis and remodelling. Baicalin also strongly inhibited the production of reactive oxygen and nitrogen species in the heart by preventing overactivation of the NADPH oxidase NOX2. Hence, the cardioprotective effects of baicalin in preventing chronic β-AR-induced HF were due to preventing the overactivation of NOX2 and generation of excessive oxidative stress. Our findings provide new mechanistic insight and suggest the therapeutic potential of baicalin as a novel drug in the treatment of chronic HF.