Jiuzhuan Huangjing Pills alleviate fatigue by preventing energy metabolism dysfunctions in mitochondria

Fatigue exerts a profound impact on human health. Jiuzhuan Huangjing Pills (JHP), comprising two functional foods, exhibits homology of medicine and food. In this study, we found that JHP improved fatigue in both in vivo and in vitro models by protecting against structural damage and functional disorders of mitochondria through the reduction of oxidative stress, thereby preventing cell death and enhancing energy metabolism. By investigating metabolomes in serum, skeletal muscle (SM), and SM mitochondria, JHP primarily mitigated oxidative stress by modulating the abundances of organic acids and lipids at multiple levels. Furthermore, we identified the anti-fatigue ingredients derived from JHP and conducted experimental verification to confirm that their pharmacodynamic effects were similar to those of JHP. Our findings suggested that JHP can serve as a candidate dietary supplement to improve fatigue by maintaining mitochondrial homeostasis through its antioxidant properties to enhance overall energy production in the body.