HHQ16, an orally active derivative of Astragaloside IV, effectively reverses infarction-induced hypertrophy and heart failure by targeting and degrading lnc4012/lnc9456 and antagonizing their effects on G3BP2/NF-κB signaling [1].

HHQ16 (100 nM, 6 hours) binds with high affinity to lnc9456 and induces its degradation in HL-1 mouse cardiomyocytes [1].

HHQ16, administered orally via gavage at doses ranging from 1 to 100 mg/kg daily for four weeks, effectively reverses heart function deterioration and structural remodeling in mice caused by left anterior descending coronary artery ligation (LADL) [1]. At a dose of 10 mg/kg orally for two weeks, HHQ16 reduces high levels of lnc9456 in the hearts of AAV-lnc9456 mice and mitigates remodeling-associated changes [1]. In the LADL-induced heart failure mouse model [1], HHQ16 improves cardiac function by increasing left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), while decreasing heart size and the heart weight to body surface area ratio (HW/BSA). It counteracts hypertrophy by reducing cell volume and aligning myocytes, and lowers levels of ANP, BNP, β-MHC, along with their hypertrophic expression.