Biotechnology Research Laboratories, Pharma & Supplemental Nutrition Solutions Vehicle, Kaneka Corporation, 1-8 Miyamae-cho, Takasago-cho, Takasago 676-8688, Japan.
Unit of Biotechnology, Hiroshima Research Center for Healthy Aging (HiHA), Graduate School of Integrated Sciences for Life, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8530, Japan.
Nutrients. 2022 Mar 4;14(5):1078. doi: 10.3390/nu14051078.
Sarcopenia is an age-related skeletal muscle atrophy. Exercise is effective in improving sarcopenia via two mechanisms: activation of skeletal muscle satellite cells (SCs) and stimulation of muscle protein synthesis. In contrast, most nutritional approaches for improving sarcopenia focus mainly on muscle protein synthesis, and little is known about SC activation. Here, we investigated the effect of lemon myrtle extract (LM) on SC activation both in vitro and in vivo. Primary SCs or myoblast cell lines were treated with LM or its derived compounds, and incorporation of 5-bromo-2′-deoxyuridine, an indicator of cell cycle progression, was detected by immunocytochemistry. We found that LM significantly activated SCs (p < 0.05), but not myoblasts. We also identified casuarinin, an ellagitannin, as the active compound in LM involved in SC activation. The structure−activity relationship analysis showed that rather than the structure of each functional group of casuarinin, its overall structure is crucial for SC activation. Furthermore, SC activation by LM and casuarinin was associated with upregulation of interleukin-6 mRNA expression, which is essential for SC activation and proliferation. Finally, oral administration of LM or casuarinin to rats showed significant activation of SCs in skeletal muscle (p < 0.05), suggesting that LM and casuarinin may serve as novel nutritional interventions for improving sarcopenia through activating SCs.
肌肉减少症是一种与年龄相关的骨骼肌萎缩。运动通过两种机制有效改善肌肉减少症：激活骨骼肌卫星细胞（SCs）和刺激肌肉蛋白合成。相比之下，大多数改善肌肉减少症的营养方法主要侧重于肌肉蛋白合成，而对于 SC 激活知之甚少。在这里，我们研究了柠檬桉提取物（LM）对体外和体内 SC 激活的影响。用 LM 或其衍生化合物处理原代 SC 或成肌细胞系，并通过免疫细胞化学检测细胞周期进程的指示剂 5-溴-2'-脱氧尿苷的掺入。我们发现 LM 可显著激活 SC（p<0.05），但不能激活成肌细胞。我们还鉴定出 casuarinin，一种鞣花单宁，是参与 SC 激活的 LM 中的活性化合物。构效关系分析表明， casuarinin 的整体结构对于 SC 激活至关重要，而不是其每个功能基团的结构。此外，LM 和 casuarinin 对 SC 的激活与白细胞介素-6 mRNA 表达的上调有关，这对于 SC 的激活和增殖至关重要。最后，LM 或 casuarinin 的口服给药显示大鼠骨骼肌中 SC 的显著激活（p<0.05），表明 LM 和 casuarinin 可作为通过激活 SC 改善肌肉减少症的新型营养干预措施。
