Astragaloside IV Reduces Sorafenib-Induced Cardiotoxicity by Inhibiting Apoptosis Through the STAT3/HIF-1α/Bcl-2...

Area of Science:

• Cardiovascular Pharmacology
• Natural Product Chemistry
• Oncology Drug Safety

Background:

• Sorafenib, a tyrosine kinase inhibitor, is vital for cancer treatment but causes significant cardiotoxicity.
• Astragaloside IV, a natural compound, exhibits known cardiovascular protective properties.
• Developing strategies to mitigate chemotherapy-induced cardiotoxicity is crucial for patient outcomes.

Purpose of the Study:

• To investigate the protective effects of Astragaloside IV against sorafenib-induced cardiotoxicity.
• To elucidate the underlying molecular mechanisms of Astragaloside IV's cardioprotective action.
• To identify novel therapeutic targets for preventing chemotherapy-related cardiac injury.

Main Methods:

• Network pharmacology and human proteome microarray screening identified key pathways and targets.
• Molecular docking and dynamics simulations assessed binding stability of Astragaloside IV.
• In vivo mouse models and in vitro cellular experiments evaluated Astragaloside IV's efficacy and mechanism.

Main Results:

• Astragaloside IV significantly improved cardiac function and reduced myocardial fibrosis, oxidative damage, and apoptosis in a mouse model.
• Mechanistically, Astragaloside IV inhibited signal transducer and activator of transcription 3 (STAT3) and hypoxia-inducible transcription factor-1α (HIF-1α) expression, while increasing B-cell lymphoma 2 (Bcl-2) expression.
• Astragaloside IV protected HL-1 cardiomyocytes from sorafenib-induced cytotoxicity and apoptosis via the STAT3/HIF-1α/Bcl-2 pathway.

Conclusions:

• Astragaloside IV effectively alleviates sorafenib-induced cardiotoxicity by inhibiting cardiomyocyte apoptosis.
• The cardioprotective mechanism involves targeting the STAT3/HIF-1α/Bcl-2 signaling pathway.
• Astragaloside IV presents a promising therapeutic strategy for preventing chemotherapy-related cardiac injury.