Xinlikang capsule ameliorates cancer-related fatigue in Lewis lung carcinoma tumor-bearing mice: association with inhibition of oxidative stress and attenuation of JNK activation and bone marrow apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Cisplatin (DDP)-exacerbated cancer-related fatigue (CRF) and myelosuppression impair patients' quality of life, and effective interventions remain limited. Xinlikang Capsule (XLK), a proprietary Chinese medicine used as adjunctive oncology therapy, has unclear effects on CRF.

AIM OF THE STUDY: To investigate the effects of XLK on CRF in Lewis lung carcinoma (LLC) tumor-bearing mice and explore its mechanisms.

MATERIALS AND

METHODS

LLC tumor-bearing mice received control, model, DDP, or DDP plus XLK low-, medium-, and high-dose treatments. Fatigue behaviors, blood counts, bone marrow histology, and bone marrow cell populations were assessed. Enzyme-linked immunosorbent assay (ELISA) measured hematopoietic factors and cytokines. Network pharmacology predicted core targets, and apoptosis, oxidative stress, mitochondrial function, and JNK/NF-κB signaling were evaluated by histological, flow cytometric, immunofluorescence, and Western blot.

RESULTS

XLK ameliorated fatigue-like behaviors, ncreased blood counts, improved marrow histology, elevated bone marrow cell populations, and modulated serum levels of hematopoietic factors and cytokines. Network pharmacology indicated apoptosis as a key pathway. XLK reduced bone marrow cell apoptosis and oxidative stress, restored mitochondrial function, downregulated apoptosis-related proteins (p-MKK4/7, p-JNK, Bax, and cleaved caspase-3), upregulated Bcl-2, inhibited NF-κB p65/IκBα phosphorylation, and reduced the co-localization of p-JNK and cleaved caspase-3.

CONCLUSION

XLK alleviates DDP-exacerbated CRF and myelosuppression in LLC tumor-bearing mice. These effects are associated with suppressing of oxidative stress, restoring of mitochondrial function, attenuation of JNK activation, reduction of bone marrow apoptosis, and concomitant inhibition of NF-κB. However, direct causal validation of JNK signaling was not performed.