Although
astragaloside IV protects from acute
myocardial infarction (AMI)-induced chronic
heart failure (CHF), the underlying mechanism of action is unclear. We determined the potential
therapeutic effect of
astragaloside IV using molecular docking approaches and validated the findings by the
ligation of the left anterior descending (LAD) coronary artery-induced AMI rat model. The interaction between
astragaloside IV and
myeloid differentiation factor 88 (MyD88) was evaluated by SwissDock. To explore the mechanisms underlying the beneficial effects of
astragaloside IV in the LAD coronary artery
ligation-induced AMI model, we administered the rats with
astragaloside IV for 4 weeks. Hemodynamic indexes were used to evaluate the degree of myocardial injury in model rats. The histopathological changes in myocardium were detected by
hematoxylin &
eosin (H&E) staining and Masson's staining. Myocardium homogenate contents of
collagen I and
collagen III were evaluated by ELISA. The level of myocardial
hydroxyproline (HYP) was determined by alkaline hydrolysis. Immunohistochemistry was used to examine
collagen I. Western blotting was used to examine relevant
proteins. As per the molecular docking study results,
astragaloside IV may act on MyD88. Furthermore,
astragaloside IV improved hemodynamic disorders, alleviated pathological changes, and reduced abnormal
collagen deposition and myocardial HYP in vivo.
Astragaloside IV significantly reduced the overexpression of TLR4, MyD88, NF-Κb, and TGF-β, which further validated the molecular docking findings. Hence,
astragaloside IV ameliorates AMI by reducing
inflammation and blocking TLR4/MyD88/NF-κB signaling. These results indicate that
astragaloside IV may alleviate AMI. PRACTICAL APPLICATIONS:
Astragaloside IV, a small active substance extracted from Astragalus membranaceus, has demonstrated potent protective effects against cardiovascular
ischemia/reperfusion,
diabetic nephropathy, and other diseases. Molecular docking experiments showed that
astragaloside IV might act on the
myeloid differentiation factor 88 (MyD88).
Astragaloside IV can effectively reduce the overexpression of TLR4, MyD88, and NF-κB p65, indicating that
astragaloside IV inhibits
inflammation via TLR4/MyD88/NF-κB signaling pathway. These results indicate that
astragaloside IV may alleviate acute
myocardial infarction.