Ginseng alleviates fatigue by inhibiting autophagy via activation of the PI3K/AKT/mTOR signaling pathway.

BACKGROUND

Panax ginseng C. A. Mey. (PG) is a commonly used traditional Chinese medicine to relieve fatigue-related symptoms. However, the underlying mechanisms by which PG alleviates fatigue are still not fully understood. This study aims to elucidate the anti-fatigue mechanism of PG in a hyperammonemia induced fatigue mouse model.

METHODS

The therapeutic effects of PG on hyperammonemia-induced fatigue mice were evaluated using behavioral assessments, including rotarod, open field, grip strength, and tail suspension tests, along with serum biochemical analysis and hematoxylin-eosin (HE) staining. To investigate the molecular mechanisms, an integrated approach combining transcriptomics, proteomics, network pharmacology, immunohistochemistry, immunofluorescence, and Western blot was employed.

RESULTS

PG significantly enhanced the exercise tolerance of hyperammonemia-induced fatigue mice, ameliorated skeletal muscle fiber atrophy, and restored the serum ammonia, creatine kinase, blood urea nitrogen, lactate dehydrogenase, and blood glucose levels. Comprehensive analysis of transcriptomics, proteomics and network pharmacology indicated that the mechanism of anti-fatigue of PG may be mediated by regulating autophagy via the PI3K/AKT signaling pathway. In addition, immunohistochemistry, Western blot, and immunofluorescence analysis confirmed that PG protected against fatigue by activating the PI3K/AKT/mTOR pathway to restore dysregulated autophagy in skeletal muscle under hyperammonemia conditions.

CONCLUSIONS

PG may alleviate fatigue by inhibiting excessive autophagy via the PI3K/AKT/mTOR pathway and restoring the protein balance within skeletal muscle.