Li-ginseng powder alleviates cancer cachexia in mice by regulating the ubiquitin-proteasome pathway and reducing inflammation.

Background: As a debilitating syndrome, cancer cachexia (CC) manifests as ongoing weight reduction and skeletal muscle atrophy, which severely compromise patients' well-being and life expectancy, with no approved treatment available to date. Rare ginsenosides such as Rh2, Rg5, Rk1, and Rh4 have been reported to modulate Nuclear factor kappa-B (NF-κB) and Signal Transducer and Activator of Transcription 3 (STAT3) activity and attenuate inflammatory signaling pathways implicated in CC progression. Li-Ginseng powder (LGP), a specially processed Methods: The anti-cachexia effects of LGP were evaluated in a BALB/c mouse model of CC and in a cellular CC model using mouse myoblast C2C12 cells. Body weight, skeletal muscle atrophy, and histopathological analyses were performed to assess Results: LGP treatment significantly attenuated body weight loss and skeletal muscle atrophy in CC mice. Mechanistically, LGP suppressed activation of the ubiquitin-proteasome pathway in the gastrocnemius muscle and reduced systemic and local inflammatory responses. Network pharmacology analysis identified NF-κB and STAT3 signaling as major targets of LGP, which was further confirmed in both muscle tissues and C2C12 cells. Consistently, LGP alleviated myotube atrophy and inhibited UPP, NF-κB, and STAT3 activation in vitro. Conclusion: These findings demonstrate that LGP exerts protective effects against CC by modulating muscle proteolysis and inflammation-related signaling pathways, highlighting its potential as a ginseng-based therapeutic strategy for CC.