Dehydrocostus lactone attenuates hyperthyroidism-induced myocardial remodeling and injury via modulation of the oxidative stress-autophagy-inflammation axis with involvement of mTOR signaling.

Hyperthyroidism-induced myocardial remodeling and dysfunction are common cardiovascular complications of excess thyroid hormone, yet effective targeted interventions remain limited. This study aimed to investigate the protective effect and underlying mechanism of dehydrocostus lactone (DHL) against hyperthyroidism-induced myocardial injury. C57BL/6 J mice were intraperitoneally injected with triiodothyronine (T3) to induce myocardial remodeling, with or without daily DHL administration. T3-exposed AC16 cardiomyocytes and pharmacological inhibitors were applied for in vitro mechanistic validation. DHL significantly ameliorated T3-induced cardiac structural abnormalities and systolic dysfunction in mice, and decreased serum levels of cardiac injury markers, without altering serum thyroid hormone levels. Meanwhile, DHL suppressed the expression of inflammatory effector molecules, including IL-6, TNF-α and ICAM-1 both in vitro and in vivo. Moreover, DHL attenuated cardiomyocyte oxidative stress and restored impaired autophagic flux. Notably, rapamycin functional validation indicated that the autophagy-regulating effect of DHL is associated with the mTOR signaling pathway. In conclusion, DHL is a promising adjunctive candidate for hyperthyroid myocardial remodeling and injury, which exerts cardioprotective effects by regulating the oxidative stress-autophagy-inflammation axis with mTOR pathway involvement.