Astragaloside IV Alleviates Myocardial Fibrosis After Myocardial Infarction through SIRT3/β-catenin/PPARγ Signaling Pathway

Abstract

Background: Myocardial fibrosis following myocardial infarction (MI) is linked to decreased cardiac function and heart failure. Astragaloside IV (AST IV), a component of traditional Chinese medicine, has shown promise in animal studies for improving cardiac function.Objectives: This study intends to investigate the role of AST IV in MI and its correlation with the sirtuin-3 (SIRT3)/β- catenin/peroxisome proliferator-activated receptor gamma (PPARγ) signaling pathway.Materials and Methods: After the establishment of an animal model of MI, 60 rats were divided into a control group, model group (MI group), positive control group (sham group), low-dose AST IV group (0.8 mg/100 g), and high-dose AST IV group (3 mg/100 g). The animals were injected once a day for 4 consecutive weeks. To further investigate the mechanism of action of AST IV, another nine rats from the model group were randomly divided into the 3TYP group (5 mg/100 g), SKL2001 group (20 μmol/L, 10 mL/kg), and T0070907 group (0.15 mg/100 g), with three rats in each group. The rats in each group were intervened once a day by intraperitoneal injection and once a day by gavage for 4 consecutive weeks. Hemodynamics, cardiac function, ventricular weight, and infarct area were assessed at 1, 2, and 4 weeks post-surgery. Myocardial collagen content in the non-infarcted area was measured, the expression rate of transforming growth factor-beta and ED-positive cells was calculated, and reverse transcription polymerase chain reaction was used to detect SIRT3, β-catenin, and PPARγ mRNA expression.Results: The left ventricular ejection fraction, short-axis shortening rate, and left ventricular mass in the model group were decreased obviously. AST IV treatment decreased systolic blood pressure, +dp/dtmax, –dp/dtmax, and left ventricular enddiastolic pressure, as well as reduced myocardial collagen deposition in rat hearts (p < 0.05). AST IV inhibited the SIRT3/β- catenin/PPARγ signaling pathway when alleviating myocardial fibrosis. Intervention with SIRT3 blocker 3-TYP, β-catenin agonist SKL2001, and PPARγ blocker T0070907 reversed the inhibitory effect of AST IV on the signaling pathway.Conclusion: AST IV exhibits significant anti-fibrotic effects, effectively reducing collagen deposition in the MI model, improving cardiac function parameters, and decreasing markers such as creatine kinase-MB. It significantly regulates SIRT3, β-catenin, and PPARγ to exert cardioprotective effects. The key mechanism involves inhibiting the SIRT3/β-catenin/PPARγ, offering an innovative strategy for post-MI treatment.

Keywords: Astragaloside IV; myocardial infarction; myocardial fibrosis; SIRT3/β-catenin/PPARγ