Neobavaisoflavone Protects H9c2 Cells Against H₂O₂-Induced Mitochondrial Dysfunction Through ALOX15/PGC1-α Axis

Area of Science:

• Cardiovascular Biology
• Oxidative Stress Research
• Natural Product Pharmacology

Background:

• Oxidative stress is a key factor in myocardial injury.
• Hydrogen peroxide (H2O2) is a common inducer of oxidative stress in cardiomyocytes.
• Natural antioxidants offer potential therapeutic benefits for heart conditions.

Purpose of the Study:

• To investigate the protective effects of Neobavaisoflavone (NBIF) against H2O2-induced oxidative stress in H9c2 cardiomyocytes.
• To elucidate the underlying molecular mechanisms, focusing on mitochondrial function and specific signaling pathways.

Main Methods:

• H9c2 cells were exposed to H2O2, with or without NBIF treatment.
• Cell viability was assessed using Cell Counting Kit-8.
• Mitochondrial membrane potential, lipid radicals, 12- and 15-hydroxyeicosatetraenoic acids (HETE), ALOX15, PGC-1α, and caspase-3 were measured.

Main Results:

• H2O2 induced significant lipid peroxidation, mitochondrial dysfunction, and apoptosis in H9c2 cells.
• NBIF treatment reversed these effects, decreasing lipid radicals and restoring mitochondrial membrane potential.
• NBIF downregulated ALOX15 expression and the production of 12- and 15-HETE, while upregulating PGC-1α and Nrf1, thereby inhibiting caspase-3 activation.

Conclusions:

• NBIF demonstrates significant cardioprotective effects against H2O2-induced oxidative injury.
• The protective mechanism involves the inhibition of the ALOX15 pathway and the enhancement of mitochondrial biogenesis via PGC-1α.
• NBIF represents a promising therapeutic agent for mitigating oxidative stress-related myocardial damage.