Astragaloside IV Alleviates H₂O₂-Induced Mitochondrial Dysfunction and Inhibits Mitophagy Via PI3K/AKT/mTOR Pathway

Area of Science:

• Cardiovascular Biology
• Mitochondrial Medicine
• Pharmacology

Background:

• Oxidative stress and mitochondrial dysfunction are key in cardiovascular disease pathology.
• The protective role of Astragaloside IV (As-IV) against mitochondrial damage is not fully understood.

Purpose of the Study:

• To investigate the protective effects of As-IV on H2O2-induced mitochondrial dysfunction in H9c2 cells.
• To elucidate the underlying mechanism of As-IV's action, focusing on mitophagy and the PI3K/AKT/mTOR pathway.

Main Methods:

• H9c2 cells were treated with H2O2 and As-IV.
• Apoptosis and reactive oxygen species (ROS) were measured via flow cytometry.
• Mitochondrial membrane potential (MMP), morphology, autophagosomes, mitochondrial dynamics, and protein expression (PINK1, Parkin, PI3K, AKT, mTOR) were assessed using microscopy and Western blot.

Main Results:

• As-IV reduced H2O2-induced apoptosis and ROS generation.
• As-IV preserved mitochondrial membrane potential and morphology, and regulated mitochondrial dynamics.
• As-IV inhibited mitophagy by decreasing autophagosome formation and PINK1/Parkin expression, while upregulating the PI3K/AKT/mTOR pathway.

Conclusions:

• As-IV exhibits protective effects against H2O2-induced mitochondrial dysfunction in cardiomyocytes.
• As-IV's mechanism involves the inhibition of mitophagy, potentially mediated by the PI3K/AKT/mTOR signaling pathway.