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Treatment of chemotherapy-induced cachexia with BST204: a multimodal validation study

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Abstract

Introduction

Chemotherapy is a major etiology of cachexia. Ginseng products are known to have various anti-cachectic and health-promoting effects, such as inhibiting inflammation and promoting energy production. In particular, BST204, purified ginseng dry extract, contains multiple ginsenosides that can reduce chemotherapy-related fatigue and toxicity.

Objectives

To investigate the effects of BST204 on the alleviation of chemotherapy-induced cachexia using a multimodal approach.

Methods

In a CT26 mouse syngeneic colon cancer model, cachexia was predominantly induced by chemotherapy with 5-fluorouracil (5-FU) than by tumor growth. BST204 at a dose of 100 or 200 mg/kg was administered to 5-FU-treated mice.

Results

BST204 significantly mitigated the decrease in tumor-excluded body weight (change in 5-FU group and BST204 groups: − 13% vs. − 6% on day 7; − 30% vs. − 20% on day 11), muscle volume (− 19% vs. − 11%), and fat volume (− 91% vs. − 56%). The anti-cachectic effect of BST204 was histologically demonstrated by an improved balance between muscle regeneration and degeneration and a decrease in muscle cross-sectional area reduction.

Conclusion

Chemotherapy-induced cachexia was biochemically and metabolically characterized by activated inflammation, enhanced oxidative stress, increased protein degradation, decreased protein stabilization, reduced glucose-mediated energy production, and deactivated glucose-mediated biosynthesis. These adverse effects were significantly improved by BST204 treatment. Overall, our multimodal study demonstrated that BST204 could effectively alleviate chemotherapy-induced cachexia.

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Acknowledgements

We thank the metabolomics core at the convergence medicine research center, asan medical center, for their support and instrumentation.

Funding

This study was supported by grants from the Asan Institute of Life Sciences, Asan Medical Center, Republic of Korea (2017IL0540, 2018IL0540); from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2017R1A2B3007567); from the Industrial Core Technology Development Program (10063475) funded by the Ministry of Trade, Industry and Energy (Korea); and by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea (HI14C1090).

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Authors

Contributions

HK: performed study design, animal experiments, sample preparation, data acquisition and analysis, and wrote the manuscript. SJK: acquired/interpreted the LC/MS–MS data. CW and SK: acquired/interpreted MRI data. ML, SKP, and JK: performed data analysis and edited the manuscript. HJY, DW, and JKK: oversaw all aspects of the research project and co-wrote the manuscript.

Corresponding authors

Correspondence to Hyun Ju Yoo, Dong-Cheol Woo or Jeong Kon Kim.

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All authors declare that he/she has no conflict of interest.

Ethical approval

This study was reviewed and approved by the Institutional Animal Care and Use Committee of the Asan Medical Institute of Convergence Science and Technology, Seoul, Korea (IACUC number: 2017-01-050). All procedures were performed according to the relevant guidelines of the National Cancer Institute.

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Kim, Hj., Kim, S.J., Woo, CW. et al. Treatment of chemotherapy-induced cachexia with BST204: a multimodal validation study. Metabolomics 17, 36 (2021). https://doi.org/10.1007/s11306-021-01781-8

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