Key result
Astragaloside IV reduces cardiac hypertrophy and fibrosis while improving LVEF and diastolic function in diabetic mice.
Why the study?
Astragaloside IV alleviates diabetes-induced endothelial dysfunction by inhibiting calpain-1, but whether this mechanism underlies its protective effect against diabetic cardiomyopathy was unknown.
Does Astragaloside IV improve cardiac hypertrophy, fibrosis, and cardiac function in a mouse model of diabetic cardiomyopathy?
Does Astragaloside IV improve cardiac hypertrophy, fibrosis, and cardiac function in a mouse model of diabetic cardiomyopathy?
Astragaloside IV ameliorates diabetic cardiomyopathy in mice by inhibiting the calpain-1/CaMKII pathway, thereby reducing intracellular Ca2+ overload, oxidative stress, and apoptosis.
Answers are grounded in this paper and cite their sources.
Astragaloside IV shows benefit in murine diabetic cardiomyopathy; leaves open translation to human therapy.
Objective Astragaloside IV (AsIV) has been reported to alleviate diabetes-induced endothelial dysfunction by inhibiting calpain-1. This study aimed to determine whether the same mechanism underlies its protective effect against diabetic cardiomyopathy (DCM). Methods At the in vivo level, calpain-1 knockout mice with the genotype Capn1 EK684−/− (Capn1 EK684 knockout mice) were used to establish a type 2 diabetic cardiomyopathy model. At the in vitro level, H9c2 cells and cardiac fibroblasts were stimulated with high glucose to construct corresponding models. Meanwhile, a calpain-1 overexpression lentivirus was constructed to assess the effect of calpain-1 on myocardial cell injury. Different doses of AsIV were then used to intervene in diabetic mice and H9c2 cells. Body weight, blood glucose, myocardial hypertrophy, myocardial fibrosis, cardiac function, Ca 2+ overload and its regulation, myocardial cell apoptosis and oxidative stress were evaluated in the current study. Results AsIV could not completely normalize blood glucose in mice, but could significantly improve cardiac systolic and diastolic function, myocardial hypertrophy and fibrosis. The beneficial effect of calpain-1 gene knockout on diabetic cardiomyopathy was similar to that of AsIV, and calpain-1 knockout did not further enhance the beneficial effect of AsIV. Calpain-1 overexpression abolished the beneficial effect of AsIV on high glucose induced H9c2 cell injury and fibroblast proliferation. In addition, the intracellular Ca 2+ overload, abnormal levels of sarco/endoplasmic reticulum Ca 2+ -ATPase 2a (SERCA2a), phosphorylation of phospholamban (p-PLN) and ryanodine receptor 2 (p-RyR2), apoptosis and oxidative stress associated with DCM were also improved by AsIV or calpain-1 knockout, and AsIV has the capacity to suppress the overactivation of calpain-1 and calcium/calmodulin-dependent protein kinase Ⅱ (CaMKII). Conclusions AsIV could ameliorate intracellular Ca 2+ overload, apoptosis, and oxidative stress by regulating the calpain-1/CaMKII pathway, thereby improving myocardial hypertrophy and fibrosis caused by diabetes mellitus.
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Zhou et al. (2026) studied Male C57BL/6N mice model of type 2 diabetic cardiomyopathy induced by high-fat diet and streptozotocin injection (n=60). Astragaloside IV (AsIV) vs. Vehicle control (0.5% sodium carboxymethyl cellulose solution), metformin (positive control) was evaluated on Cardiac hypertrophy and fibrosis markers and function: heart weight/body weight ratio (HW/BW), cross section area (CAS), fibrosis area, left ventricular ejection fraction (LVEF), fractional shortening (LVFS), left ventricular internal dimensions (LVIDd, LVIDs), mitral valve E/A ratio, heart rate (HR) (p=AsIV groups showed significant improvement versus T2DM controls (p<0.05 for multiple endpoints)). Astragaloside IV at 50-100 mg/kg improved cardiac hypertrophy (cross section area 1.83-fold increased in diabetes reduced by AsIV), fibrosis (fibrosis area 3.96-fold increased reduced by AsIV), and partially reversed systolic dysfunction (increased LVEF, LVFS) and diastolic dysfunction (increased E/A) in diabetic mice after 8 weeks.
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