SEARCHOTHERpreclinical research, biomedical research

other·preclinical research, biomedical research, oncology, nutrition, micronutrients·PMC10497166

The combination of quercetin and leucine synergistically improves grip strength by attenuating muscle atrophy by multiple mechanisms in mice exposed to cisplatin

PLOS ONE · 9 authors, 6 centres

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TL;DR

This preclinical mouse study tested the combination of quercetin and leucine against cisplatin-induced muscle atrophy. The combination treatment synergistically improved grip strength and attenuated muscle loss more than either supplement alone.

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This study investigated the effects of combining quercetin and leucine on cisplatin (CDDP)-induced muscle atrophy and cancer-related fatigue (CRF) in male BALB/c mice. Mice were treated for 9 weeks with CDDP and various combinations of quercetin and two dietary leucine levels. The central result was that quercetin combined with leucine synergistically improved maximum grip strength and additively increased body, fat, and muscle weights. Mechanistically, the combination decreased activation of the Akt/FoxO1/atrogin-1/MuRF1 protein degradation pathway and increased activation of the mTOR and E2F-1 protein synthesis and cell growth pathways in muscle tissue. The study had limitations, including the use of an animal model with indirect human relevance and the need for further cellular studies to confirm mechanisms like E2F-1 signaling. The implication is that this nutritional combination may help mitigate chemotherapy-induced muscle weakness without compromising anticancer efficacy.

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other

SPECIALTY

preclinical research

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ORIGINAL PAPER

PMC10497166

The combination of quercetin and leucine synergistically improves grip strength by attenuating muscle atrophy by multiple mechanisms in mice exposed to cisplatin

PLOS ONE

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ABSTRACT

Both quercetin and leucine have been shown to exert moderately beneficial effects in preventing muscle atrophy induced by cancers or chemotherapy. However, the combined effects of quercetin and leucine, as well as the possible underlying mechanisms against cisplatin (CDDP)-induced muscle atrophy and cancer-related fatigue (CRF) remain unclear. To investigate the issues, male BALB/c mice were randomly assigned to the following groups for 9 weeks: Control, CDDP (3 mg/kg/week), CDDP+Q (quercetin 200 mg/kg/day administrated by gavage), CDDP+LL (a diet containing 0.8% leucine), CDDP+Q+LL, CDDP+HL (a diet containing 1.6% leucine), and CDDP+Q+HL. The results showed that quercetin in combination with LL or HL synergistically or additively attenuated CDDP-induced decreases in maximum grip strength, fat and muscle mass, muscle fiber size and MyHC level in muscle tissues. However, the combined effects on locomotor activity were less than additive. The combined treatments decreased the activation of the Akt/FoxO1/atrogin-1/MuRF1 signaling pathway (associated with muscle protein degradation), increased the activation of the mTOR and E2F-1 signaling pathways (associated with muscle protein synthesis and cell cycle/growth, respectively). The combined effects on signaling molecules present in muscle tissues were only additive or less. In addition, only Q+HL significantly increased glycogen levels compared to the CDDP group, while the combined treatments considerably decreased CDDP-induced proinflammatory cytokine and MCP-1 levels in the triceps muscle. Using tumor-bearing mice, we demonstrated that the combined treatments did not decrease the anticancer effect of CDDP. In conclusion, this study suggests that the combination of quercetin and leucine enhanced the suppressed effects on CDDP-induced muscle weakness and CRF through downregulating muscle atrophy and upregulating the glycogen level in muscle tissues without compromising the anticancer effect of CDDP. Multiple mechanisms, including regulation of several signaling pathways and decrease in proinflammatory mediator levels in muscles may contributed to the enhanced protective effect of the combined treatments on muscle atrophy.

CITATION EXPORT

Te-Hsing Hsu, Ting-Jian Wu, Yu-An Tai et al.. The combination of quercetin and leucine synergistically improves grip strength by attenuating muscle atrophy by multiple mechanisms in mice exposed to cisplatin. PLOS ONE. (2023). https://doi.org/10.1371/journal.pone.0291462

AUTHORS

9 · 6 CENTRES

Te-Hsing Hsu, Ting-Jian Wu, Yu-An Tai, Chin-Shiu Huang, Jiunn-Wang Liao, Shu-Lan Yeh, Hiroshi Kaji, Hiroshi Kaji, Hiroshi Kaji

1 Department of Nutritional Science, Chung Shan Medical University, Taichung, Taiwan
2 Institute of medicine, Chung Shan Medical University, Taichung, Taiwan
3 Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan
4 Graduate Institute of Veterinary Pathology, College of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan
5 Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan
Kindai University Faculty of Medicine, JAPAN

EDITOR / REVIEWER

Hiroshi Kaji