Research Center of Traditional Chinese Medicine, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin 130021, P.R. China.
Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, Jilin 130021, P.R. China.
Mol Med Rep. 2021 May;23(5). doi: 10.3892/mmr.2021.11945. Epub 2021 Mar 2.
Muscle atrophy, a side effect from administration of the anti‑inflammatory medication dexamethasone (DEX), is preventable by concomitant administration of the major monomeric constituent of C.A. Meyer, 20(S)‑ginsenoside Rg3 (S‑Rg3). Putative S‑Rg3‑associated prevention of DEX‑induced muscle atrophy may involve S‑Rg3 mitigation of DEX‑induced mitochondrial dysfunction. In the present study, MTT assays revealed enhanced cell viability following S‑Rg3 treatment of DEX‑injured C2C12 myotubes. Subsequent PCR and western blotting results demonstrated S‑Rg3‑induced reduction of expression of muscle atrophy F‑box protein (atrogin‑1) and muscle RING‑finger protein‑1, proteins previously linked to muscle atrophy. Additionally, S‑Rg3 treatment of DEX‑injured myotubes led to aggregation of Rg3 monomers in cells and dose‑dependent increases in cellular mitochondrial basal respiratory oxygen consumption rate and intracellular ATP levels compared with their levels in untreated DEX‑injured myotubes. In addition, S‑Rg3 treatment significantly reversed DEX‑induced reductions of expression of key mitochondrial respiratory electron transport chain subunits of protein complexes II, III and V in DEX‑injured myotube cells. Furthermore, S‑Rg3 alleviation of mitochondrial dysfunction associated with DEX‑induced injury of C2C12 myotubes was linked to S‑Rg3‑associated decreases in both forkhead box O3 (FoxO3) protein expression and phosphorylation of AMP‑activated protein kinase (AMPK). Collectively, these results implicate S‑Rg3 modulation of signaling within the AMPK‑FoxO3 pathway as a putative mechanism underlying S‑Rg3 alleviation of DEX‑induced muscle atrophy.
肌肉萎缩是一种由抗炎药物地塞米松（DEX）引起的副作用，可以通过同时给予 C.A. Meyer 的主要单体成分 20(S)-人参皂苷 Rg3（S-Rg3）来预防。推测 S-Rg3 预防 DEX 诱导的肌肉萎缩可能涉及 S-Rg3 减轻 DEX 诱导的线粒体功能障碍。在本研究中，MTT 分析显示 S-Rg3 处理 DEX 损伤的 C2C12 肌管后细胞活力增强。随后的 PCR 和 Western blot 结果表明，S-Rg3 诱导的肌肉萎缩 F-框蛋白（atrogin-1）和肌肉 RING 指蛋白-1 表达减少，这两种蛋白先前与肌肉萎缩有关。此外，与未处理的 DEX 损伤肌管相比，S-Rg3 处理 DEX 损伤的肌管导致 Rg3 单体在细胞中聚集，细胞内基础呼吸耗氧量和细胞内 ATP 水平呈剂量依赖性增加。此外，S-Rg3 处理显著逆转了 DEX 诱导的 DEX 损伤肌管中蛋白质复合物 II、III 和 V 的关键线粒体呼吸电子传递链亚基的表达减少。此外，S-Rg3 缓解与 DEX 诱导的 C2C12 肌管损伤相关的线粒体功能障碍与 S-Rg3 相关的叉头框 O3（FoxO3）蛋白表达和 AMP 激活蛋白激酶（AMPK）磷酸化减少有关。总之，这些结果表明 S-Rg3 调节 AMPK-FoxO3 通路中的信号转导可能是 S-Rg3 缓解 DEX 诱导的肌肉萎缩的潜在机制。
