Ginsenoside Rg5 Improves Radiation-Induced Heart Injury via PPARG/PDK1/AKT1 Pathway.

Area of Science:

• Cardiovascular Research
• Radiation Oncology
• Pharmacology

Background:

• Radiation therapy can cause significant cardiac damage, leading to radiation-induced heart injury (RIHI).
• The therapeutic potential of Ginsenoside Rg5 (G-Rg5), a ginseng extract, for RIHI remains largely unexplored.
• Understanding the molecular mechanisms underlying G-Rg5's effects is crucial for its clinical application.

Purpose of the Study:

• To investigate the protective effects of G-Rg5 against radiation-induced heart injury.
• To elucidate the underlying molecular mechanisms and key molecular targets of G-Rg5 in mitigating RIHI.
• To explore the role of the PPARG/PDK1/AKT1 pathway in G-Rg5's cardioprotective action.

Main Methods:

• Employed in vivo and in vitro studies to assess G-Rg5's impact on radiation-induced cardiac damage.
• Utilized network pharmacology to identify potential therapeutic targets and pathways.
• Validated the involvement of the peroxisome proliferator activated receptor gamma (PPARG)/phosphoinositide-dependent protein kinase 1 (PDK1)/AKT serine/threonine kinase 1 (AKT1) pathway through various experimental assays, including chromatin immunoprecipitation and luciferase reporter assays.

Main Results:

• G-Rg5 treatment significantly alleviated radiation-induced cardiomyocyte apoptosis and cardiac functional impairment.
• G-Rg5 upregulated peroxisome proliferator activated receptor gamma (PPARG) expression, which suppressed phosphoinositide-dependent protein kinase 1 (PDK1) transcription.
• This modulation enhanced AKT serine/threonine kinase 1 (AKT1) phosphorylation, demonstrating a protective effect that was dependent on PPARG activity.

Conclusions:

• Ginsenoside Rg5 (G-Rg5) exhibits significant cardioprotective effects against radiation-induced heart injury.
• The mechanism involves the upregulation of PPARG, leading to enhanced AKT1 phosphorylation and subsequent mitigation of apoptosis and functional decline.
• G-Rg5 demonstrates considerable potential as a therapeutic agent for preventing or treating radiation-induced heart injury.