A reserpine-induced spleen-deficiency-like state is associated with aggravated cancer cachexia and metabolic-marker alterations following Liu-Jun-Zi Decoction treatment in mice

Background Cancer cachexia is a fatal complication characterized by systemic energy dysregulation. In traditional Chinese medicine (TCM), spleen deficiency (SD) is a syndrome construct describing impaired digestive, nutritive, and functional states rather than anatomical splenic dysfunction. This study examined whether a reserpine-induced SD-like state was associated with more severe cachexia-related phenotypes in Lewis lung carcinoma-bearing mice and whether Liu-Jun-Zi Decoction (LJZD) treatment was associated with changes in these outcomes. Methods A combined disease-syndrome mouse model of SD-type lung cancer cachexia was established using reserpine combined with Lewis lung carcinoma cell inoculation. Body weight, tumor-free body weight, grip strength, hanging time, and tumor growth were assessed. Histopathological changes in tumor, adipose, and muscle tissues were observed by H&E staining. Selected proteins and transcripts related to tumor glycolysis (c-MYC and HK2), adipose remodeling (UCP1 and HSL), muscle atrophy (MAFbx and MuRF1), and inflammation (LCN2) were assessed by immunohistochemistry, Western blotting, and/or RT-qPCR. Serum levels of norepinephrine (NE), TNF-α, IL-6, and LCN2 were measured by ELISA, and let-7g microRNA expression was assessed by RT-qPCR. Results Relative to the tumor-only (TM) group, mice exposed to both reserpine and tumor challenge (ST) showed lower total and tumor-free body weight, poorer physical performance, and larger tumors. LJZD treatment in the ST background was associated with improvements in these phenotypes and a reduction in tumor burden. The ST group also showed higher c-MYC/HK2, TNF-alpha/IL-6/LCN2, HSL/UCP1, and MAFbx/MuRF1 abundance and lower let-7g microRNA expression than the TM group; these marker changes were attenuated in the LJZD-treated group. Conclusion In this reserpine-based mouse model, the SD-like state was associated with more severe cachexia-related phenotypes and changes in selected glycolysis-associated markers in tumor tissue, systemic inflammation, adipose remodeling, and muscle atrophy. LJZD treatment was associated with partial normalization of these markers.