Long-Term Bergamot Essential Oil Inhalation Alleviates Prolonged Exercise-Induced Fatigue in Rats Through the Modulation of Skeletal Muscle Inflammation, Oxidative Stress, and Regeneration-Related Signaling

Excessive exercise without adequate recovery can induce prolonged fatigue, accompanied by skeletal muscle inflammation, oxidative stress, and impaired repair. Bergamot essential oil (BEO), a citrus-derived volatile essential oil, has been reported to have anti-inflammatory and antioxidant activities, but its effects on exercise-induced prolonged fatigue remain unclear. This study investigated the fatigue-relieving effects of long-term inhalation of BEO and its major constituents in a rat model of prolonged exercise-induced fatigue, with emphasis on skeletal muscle regulation. Rats were subjected to progressive exercise loading and exposed daily to BEO or its main components, followed by behavioral, biochemical, histological, transcriptional, and protein analyses. BEO inhalation significantly improved swimming endurance and alleviated fatigue-related physiological disturbances. In skeletal muscle, BEO reduced IL-1β and IL-6 levels, attenuated transcriptional changes in NF-κB/NLRP3-related inflammatory markers, decreased MDA accumulation, and enhanced GSH-Px activity. BEO also modulated muscle repair-related markers by reversing the abnormal elevation of Myod1 and restoring Myog mRNA expression. These effects were accompanied by increased Igf1 expression, restored PI3K protein expression, enhanced PI3K phosphorylation, and increased inhibitory phosphorylation of GSK3β. Overall, BEO alleviated prolonged exercise-induced fatigue by attenuating skeletal muscle inflammation, oxidative stress, and repair-related dysregulation, supporting its potential as a non-oral aromatic intervention for fatigue recovery.