Astragaloside IV prevents acute myocardial infarction by inhibiting the TLR4/MyD88/NF‐κB signaling pathway

Abstract

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.

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“…As previously mentioned, the model of AMI in rats was constructed by ligating the left anterior descending (LAD) coronary artery [ 29 ]. Briefly, all rats were anesthetized with isoflurane and equipped with respirators to reduce the pain.…”

Kaempferol‐3‐ O ‐rutinoside exerts cardioprotective effects through NF‐ κ B/NLRP3/Caspase‐1 pathway in ventricular remodeling after acute myocardial infarction

“…The rat model of AMI was established by ligation of the left anterior descending artery (LAD) coronary artery as previously described (Shi et al, 2021). Briefly, rats were anesthetized with isoflurane and equipped with a respirator to reduce the pain.…”

“…Left ventricular myocardium containing myocardial infarction area was collected, fixed with 4% paraformaldehyde, and paraffin‐embedded tissue was prepared into a 5 μm thick tissue sections (Shi et al, 2021). Hematoxylin–eosin (HE) staining and Masson staining were used to observe the pathological changes, collagen deposition in the myocardial interstitium, and collagen volume fraction (CVF).…”

“…Thirty minutes after the last gavage of the corresponding solution, the rats were anesthetized with sodium pentobarbital, and polystyrene was catheterized through the right carotid artery into the left ventricle of the heart (Shi et al, 2021). Hemodynamic indicators including LVSP, LVEDP, +dp/dtmax, and -dp/dtmax were detected by PowerLab instrument.…”