Protective Effects of Ganoderma Triterpenoids Supplementation Against Myocardial Injury in Exhaustion Exercise Mice via Regulation of the Keap1/Nrf2/ <scp>HO</scp> ‐1 Pathway

Exhaustive physical exercise, while promoting cardiovascular fitness, can paradoxically lead to excessive oxidative stress, systemic fatigue, and myocardial injury. Despite increasing awareness of exhaustion exercise myocardial damage, effective preventive strategies remain limited. Natural bioactive compounds with antioxidant and antiapoptotic properties have gained attention as potential interventions. Among them, triterpenoids derived from <i>Ganoderma lucidum</i> triterpenoids (GLTs) are notable for their potent free radical scavenging and cytoprotective effects. However, their cardioprotective potential under conditions of exhaustion exercise oxidative stress has not been fully elucidated. This study explores the antifatigue potential of GLTs and elucidates their underlying mechanisms through the establishment of a mouse model of exhaustion exercise via exhaustive treadmill running. This study showed that GLTs significantly alleviated exhaustion exercise by reducing serum fatigue biomarkers (CK, BUN, and LDH) and improving myocardial histopathological conditions. GLTs enhanced antioxidant capacity by decreasing MDA levels, increasing SOD and CAT activities, and elevating GSH content, thereby mitigating oxidative stress. Additionally, GLTs regulated apoptosis by downregulating Bax and Caspase-3 expression, upregulating Bcl-2 levels, and reducing the Bax/Bcl-2 ratio. Mechanistically, these effects were associated with activation of the Keap1/Nrf2/HO-1 signaling pathway. Collectively, this study provides new insights into the context-specific role of GLTs in protecting against exhaustion exercise myocardial injury. Our findings highlight the therapeutic potential of GLTs as a natural antioxidant strategy for mitigating oxidative stress, delaying fatigue, and preserving cardiac function under conditions of intensive physical exertion.