ScholarWorks@숙명여자대학교

초록

Purpose: Muscle atrophy is a prevalent complication among cancer patients undergoing chemotherapy, often resulting in treatment interruption and a decline in the quality of life. Chemotherapeutic agents, such as FOLFIRI (a combination of 5-fluorouracil, leucovorin, and irinotecan), disrupt muscle homeostasis by impairing protein synthesis, increasing proteolysis, and inducing mitochondrial damage. This study investigated the potential protective effects of kuraridinol, a flavonoid compound derived from Sophora flavescens, against chemotherapy-induced muscle atrophy and mitochondrial dysfunction. Methods: C2C12 myoblasts were induced to differentiate in media supplemented with kuraridinol (0, 0.01, 0.1, and 1 ng/mL), without or with FOLFIRI. Myogenic differentiation was assessed by immunostaining with an anti-myosin heavy chain (MHC) antibody, and the number of multinucleated MHC-positive myotubes was quantified. The expression levels of myogenic markers and protein degradation-related genes were measured using quantitative reverse transcriptase polymerase chain reaction and western blot analysis. The in vivo efficacy was evaluated by exposing wild-type AB* zebrafish embryos to FOLFIRI alone or with kuraridinol, followed by immunostaining to visualize slow and fast muscle fibers. In addition, Tg (Xla.Eef1a1:mito-EGFP) zebrafish expressing mitochondria-targeted EGFP were used to examine the mitochondrial morphology. Results: Kuraridinol significantly promoted MHC-positive multinucleated myotubes and upregulated key myogenic markers, including myogenic differentiation 1 (myoD), myogenic factor 4 (myogenin), and MHC isoforms (Myh1, Myh2, Myh4, and Myh7). Furthermore, using FOLFIRI-induced muscle atrophy models in zebrafish and C2C12 cells, kuraridinol restored the muscle structure and mitochondrial integrity damaged by chemotherapy, while attenuating muscle protein degradation through suppression of the nuclear factor-κB, forkhead box O1, and p38 mitogen-activated protein kinase signaling pathways. Conclusion: Kuraridinol protects against chemotherapy-induced muscle atrophy by enhancing myogenesis, suppressing proteolysis, and maintaining mitochondrial integrity. Kuraridinol is a potential nutritional candidate for preventing or mitigating chemotherapy-induced muscle wasting. © 2025 The Korean Nutrition Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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