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
Abstract
BackgroundCancer 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.MethodsA 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.ResultsRelative 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.ConclusionIn 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.
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BibTeX
@article{zhu2026reserpineinduced,
title = {{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}},
author = {Shilong Zhu and Yazhou Sang and Yijun Wang and Qingyu Mao and Mengying Lei and Jiapan Lv and Dan Yang and Yulong Chen and Yaosong Wu},
journal = {Frontiers in Oncology},
year = {2026},
month = nov,
doi = {10.3389/fonc.2026.1966810},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1966810},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Shilong Zhu
AU - Yazhou Sang
AU - Yijun Wang
AU - Qingyu Mao
AU - Mengying Lei
AU - Jiapan Lv
AU - Dan Yang
AU - Yulong Chen
AU - Yaosong Wu
PY - 2026
DA - 2026/11/06
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1966810
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1966810
AB - BackgroundCancer 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.MethodsA 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.ResultsRelative 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.ConclusionIn 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.
SN - 2234-943X
ER -