Research Center of Traditional Chinese Medicine, Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China.
Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, China.
Phytomedicine. 2024 Nov;134:155964. doi: 10.1016/j.phymed.2024.155964. Epub 2024 Aug 15.
High glucose levels are a primary cause of diabetes-associated cellular dysfunction and tissue damage. Muscles are the key insulin target organ and therefore, have a high level of sensitivity to hyperglycemia. Our previous study revealed that 20(S)-ginsenoside Rg3 (S-Rg3) is a monomer with a good myogenic differentiation effect in ginsenoside. Furthermore, it can alleviate dexamethasone-induced muscle atrophy by protecting mitochondrial function. However, whether S-Rg3 is effective for diabetic-induced muscle atrophy has not been reported.
This study aimed to investigate the protective effect of S-Rg3 on diabetic-induced muscle atrophy.
C2C12 myoblasts, Drosophila, and mice were used as model systems, and the protective effect of S-Rg3 on diabetes was evaluated by assessing the levels of glucose and lipids. Furthermore, H&E, toluidine blue, Giemsa, and immunofluorescence staining were performed to detect the effects of S-Rg3 on muscle atrophy and myogenic differentiation. Moreover, the effects of S-Rg3 on mitochondrial morphology and function were also evaluated by electron microscopy, flow cytometry, and Seahorse. In addition, the underlying pathways of S-Rg3 effects were detected by Western blot. The related inhibitors and gene mutations in Drosophila were used for validation.
The analysis of diabetic mice model fed with a high-fat diet (HFD) and high glucose (HG) revealed that in the injured C2C12 myoblasts, S-Rg3 treatment significantly reduced the levels of triglycerides and glucose. Furthermore, it promoted the differentiation of myoblasts and inhibited mitochondrial dysfunction. In the Drosophila HG and HFD diabetic model, S-Rg3 reduced triglyceride and trehalose levels, increased climbing distance values, promoted myoblasts differentiation, preserved mitochondrial function, and inhibited muscle atrophy. Mechanistically, the beneficial effects of S-Rg3 were at least partially associated with the phosphorylation of AMPK and FoxO3 together with the inhibition of Smad3 phosphorylation, this pathway was validated by the UAS-AMPKα-RNAi Drosophila model.
In summary, this study revealed mechanistic insights into how S-Rg3 protects against diabetes-associated muscle atrophy in cells, Drosophila, and mice.
高血糖是糖尿病相关细胞功能障碍和组织损伤的主要原因。肌肉是胰岛素的主要靶器官，因此对高血糖非常敏感。我们之前的研究表明，20(S)-人参皂苷 Rg3（S-Rg3）是一种单体，在人参皂苷中具有良好的成肌分化作用。此外，它可以通过保护线粒体功能来缓解地塞米松诱导的肌肉萎缩。然而，S-Rg3 是否对糖尿病引起的肌肉萎缩有效尚未报道。
本研究旨在探讨 S-Rg3 对糖尿病引起的肌肉萎缩的保护作用。
使用 C2C12 成肌细胞、果蝇和小鼠作为模型系统，通过评估葡萄糖和脂质水平来评估 S-Rg3 对糖尿病的保护作用。此外，通过 H&E、甲苯胺蓝、吉姆萨和免疫荧光染色来检测 S-Rg3 对肌肉萎缩和成肌分化的影响。此外，还通过电子显微镜、流式细胞术和 Seahorse 评估了 S-Rg3 对线粒体形态和功能的影响。此外，通过 Western blot 检测 S-Rg3 作用的相关途径，并用果蝇中的相关抑制剂和基因突变进行验证。
对高脂肪饮食（HFD）和高葡萄糖（HG）喂养的糖尿病小鼠模型的分析表明，在受损的 C2C12 成肌细胞中，S-Rg3 处理可显著降低甘油三酯和葡萄糖水平。此外，它促进成肌细胞分化并抑制线粒体功能障碍。在果蝇 HG 和 HFD 糖尿病模型中，S-Rg3 降低了甘油三酯和海藻糖水平，增加了攀爬距离值，促进了成肌细胞分化，维持了线粒体功能，并抑制了肌肉萎缩。在机制上，S-Rg3 的有益作用至少部分与 AMPK 和 FoxO3 的磷酸化以及 Smad3 磷酸化的抑制有关，该途径通过 UAS-AMPKα-RNAi 果蝇模型得到验证。
总之，本研究揭示了 S-Rg3 如何在细胞、果蝇和小鼠中防止与糖尿病相关的肌肉萎缩的机制见解。
