Department of Biochemistry, School of Medicine, Kaohsiung Medical University, Kaohsiung, 807378, Taiwan.
Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, 807378, Taiwan.
Mol Nutr Food Res. 2024 Jul;68(14):e2300685. doi: 10.1002/mnfr.202300685. Epub 2024 Jun 11.
Kaempferol (KMP), a bioactive flavonoid compound found in fruits and vegetables, contributes to human health in many ways but little is known about its relationship with muscle mass. The effect of KMP on C2C12 myoblast differentiation and the mechanisms that might underlie that effect are studied.
This study finds that KMP (1, 10 µM) increases the migration and differentiation of C2C12 myoblasts in vitro. Studying the possible mechanism underlying its effect on migration, the study finds that KMP activates Integrin Subunit Beta 1 (ITGB1) in C2C12 myoblasts, increasing p-FAK (Tyr398) and its downstream cell division cycle 42 (CDC42), a protein previously associated with cell migration. Regarding differentiation, KMP upregulates the expression of myosin heavy chain (MHC) and activates IGF1/AKT/mTOR/P70S6K. Interestingly, pretreatment with an AKT inhibitor (LY294002) and siRNA knockdown of IGF1R leads to a decrease in cell differentiation, suggesting that IGF1/AKT activation is required for KMP to induce C2C12 myoblast differentiation.
Together, the findings suggest that KMP enhances the migration and differentiation of C2C12 myoblasts through the ITG1B/FAK/paxillin and IGF1R/AKT/mTOR pathways. Thus, KMP supplementation might potentially be used to prevent or delay age-related loss of muscle mass and help maintain muscle health.
山奈酚（KMP）是一种存在于水果和蔬菜中的生物活性类黄酮化合物，它以多种方式促进人体健康，但人们对其与肌肉质量的关系知之甚少。本研究旨在探讨 KMP 对 C2C12 成肌细胞分化的影响及其潜在机制。
本研究发现，KMP（1、10μM）可促进 C2C12 成肌细胞的体外迁移和分化。在研究其对迁移的潜在作用机制时，发现 KMP 可激活 C2C12 成肌细胞中的整合素亚基β 1（ITGB1），增加 p-FAK（Tyr398）及其下游细胞分裂周期蛋白 42（CDC42）的表达，CDC42 是一种与细胞迁移相关的蛋白。关于分化，KMP 可上调肌球蛋白重链（MHC）的表达，并激活 IGF1/AKT/mTOR/P70S6K。有趣的是，用 AKT 抑制剂（LY294002）预处理和 IGF1R 的 siRNA 敲低可导致细胞分化减少，表明 IGF1/AKT 的激活是 KMP 诱导 C2C12 成肌细胞分化所必需的。
综上所述，这些发现表明 KMP 通过 ITG1B/FAK/paxillin 和 IGF1R/AKT/mTOR 通路增强 C2C12 成肌细胞的迁移和分化。因此，KMP 的补充可能有助于预防或延缓与年龄相关的肌肉质量损失，并有助于维持肌肉健康。
