Artemisinin, an anti-malarial agent, inhibits rat cardiac hypertrophy via inhibition of NF-κB signaling.

The nuclear factor (NF)-κB signaling pathway is an important intracellular mediator of cardiac hypertrophy. Recent studies have indicated that the anti-malarial agent artemisinin has the ability to inhibit NF-κB activation. We hypothesized that artemisinin would suppress cardiac hypertrophy by inhibiting NF-κB signal pathways. We tested this hypothesis using primary cultured rat cardiac myocytes and well-established rat models of cardiac hypertrophy. Artemisinin blocked angiotensin II-induced cardiac hypertrophy in vitro in a concentration-dependent manner. Furthermore, artemisinin protected against rat cardiac hypertrophy induced by transaortic constriction (TAC), as assessed by heart weight/body weight and lung weight/body weight ratios, echocardiographic parameters, and gene expression of hypertrophic markers. Electrophoretic mobility shift assays revealed increased NF-κB binding activity in cardiac nuclear extracts of banded rats that was prevented by artemisinin treatment. Banded rats treated with oral artemisinin, compared with untreated rats, showed significantly decreased the levels of IL-6, TNF-α and MCP-1 mRNA expression and increased protein levels of IκB-α, which forms a cytoplasmic inactive complex with the p65-p50 heterodimeric complex. The effect of artemisinin on cardiac hypertrophy was blocked after IκB-α was silenced by transfection of cardiomyocytes with IκB-α siRNA. Our results indicate that artemisinin inhibits cardiomyocyte growth by interfering with NF-κB signaling.