Tectochrysin alleviates Ang II-induced pathological cardiac hypertrophy by binding to STING and inhibiting...

Angiotensin II (Ang II)-induced cardiac inflammation plays a pivotal role in the pathogenesis of pathological cardiac hypertrophy and hypertension-related heart failure. Tectochrysin (Tec) is a flavonoid natural compound exhibiting significant anti-inflammatory activity. However, the role of Tec in hypertensive heart failure and its molecular targets remain unclear.

The therapeutic efficacy of Tec was assessed in the Ang II-induced mouse model using echocardiography, histopathological staining, and serological tests. Its anti-hypertrophic effect was further examined in vitro by phalloidin staining. Investigate the mechanism of action of Tec through transcriptome sequencing. The interaction of Tec with STING was detected by DARTS, CETSA, and SPR assays. Western blotting assay detected the effect of Tec on Ang II-induced activation of the STING/NFκB pathway. The functional dependency of Tec on STING was demonstrated using the STING inhibitor H151.

In vivo experiments confirmed that Tec alleviates Ang II-induced myocardial inflammation, pathological hypertrophy, myocardial fibrosis, and cardiac dysfunction. Further in vitro studies revealed the efficacy of Tec in inhibiting cardiomyocyte hypertrophy. Mechanistically, Tec significantly suppressed Ang II-induced activation of the STING/NFκB signalling pathway by targeting STING. Crucially, administration of the STING inhibitor H151 alleviates pathological myocardial hypertrophy, however its use diminishes the therapeutic effect of Tec.

Our findings confirmed that Tec may represent a promising lead compound targeting STING for pathological cardiac hypertrophy.