白桦脂酸可改善石膏固定的骨骼肌萎缩，但不能改善去神经诱导的骨骼肌萎缩

JCSM rapid communications Pub Date : 2024-04-01 DOI:10.1002/rco2.89

Yuki Enoki, Yuki Kanezaki, Isamu Takahata, Kazuaki Taguchi, Kazuaki Matsumoto

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摘要

背景萜类化合物具有多种生理活性，因此作为骨骼肌萎缩的治疗药物已受到关注。本研究筛选了四种萜类化合物在培养细胞中对肌肉萎缩的治疗潜力，并评估了白桦脂酸在两种废用性肌肉萎缩模型中的有效性。方法在细胞培养实验中使用 C2C12 细胞作为骨骼肌模型。给两种不同的肌肉萎缩小鼠模型（使用坐骨神经去神经和铸造法建立）注射白桦脂酸（100 毫克/千克，每天两次），为期 7 天。结果在肌管实验中，白桦脂酸和熊果酸显著抑制了atrogin-1和myostatin的mRNA表达（P< 0.05）。在 C2C12 肌管的分化阶段，桦木酸可明显提高 myoD 和 myogenin 的 mRNA 表达水平（P < 0.05）。此外，凋亡素和鸢尾素也在白桦脂酸的作用下明显增加（P分别为0.05和0.01）。因此，将白桦脂酸用于上述肌肉萎缩模型。白桦脂酸不能抑制去神经模型中观察到的骨骼肌重量的减少。然而，白桦脂酸却能明显抑制在石膏固定骨骼肌萎缩模型中观察到的胫骨前肌（TA）和趾长伸肌（EDL）重量和握力的下降（TA：Cast + Veh vs. EDL：Cast + Bet = 42.6 ± 2.5 ± 2.5）。铸塑 + Bet = 42.6 ± 1.0 vs. 46.0 ± 0.8 mg，P < 0.01；EDL：铸塑 + Veh vs. 铸塑 + Bet = 9.0 ± 0.4 vs. 11.3 ± 0.5 mg，P < 0.01；握力：铸塑 + Veh vs. 铸塑 + Bet = 9.0 ± 0.4 vs. 11.3 ± 0.5 mg，P < 0.01）：Cast + Veh vs. Cast + Bet = 222 ± 4.8 vs. 245 ± 3.6 g，P < 0.05）。此外，白桦脂酸还能部分抑制骨骼肌横截面积的减少。结论白桦脂酸可缓解石膏模型肌肉萎缩，具有治疗固定失用性骨骼肌萎缩的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Betulinic acid ameliorates cast-immobilized skeletal muscle atrophy but not denervation-induced skeletal muscle atrophy

Background

Terpenoids have gained attention as therapeutic agents for skeletal muscle atrophy owing to their various physiological activities. In this study, we screened four terpenoids for their therapeutic potential against muscle atrophy in cultured cells and evaluated the effectiveness of betulinic acid in two disuse muscle atrophy models.

Methods

C2C12 cells were used as the skeletal muscle model in cell culture experiments. Betulinic acid (100 mg/kg, twice daily) was administered to two different mouse models of muscle atrophy (established using the sciatic denervation and casting methods) for 7 days.

Results

In myotube experiments, the mRNA expression of atrogin-1 and myostatin was significantly suppressed by betulinic and ursolic acids (P < 0.05). In the differentiation phase of C2C12 myotubes, the mRNA expression levels of myoD and myogenin were significantly increased by betulinic acid (P < 0.05). In addition, apelin and irisin were also significantly increased by betulinic acid (P < 0.05 and 0.01, respectively). Consequently, betulinic acid was administered to the aforementioned muscle atrophy models. Betulinic acid did not inhibit the decrease in skeletal muscle weight observed in the denervation model. However, it significantly inhibited the decrease in tibialis anterior (TA) and extensor digitorum longus (EDL) weights and grip strength observed in the cast-immobilized skeletal muscle atrophy model (TA: Cast + Veh vs. Cast + Bet = 42.6 ± 1.0 vs. 46.0 ± 0.8 mg, P < 0.01; EDL: Cast + Veh vs. Cast + Bet = 9.0 ± 0.4 vs. 11.3 ± 0.5 mg, P < 0.01; grip strength: Cast + Veh vs. Cast + Bet = 222 ± 4.8 vs. 245 ± 3.6 g, P < 0.05). In addition, betulinic acid administration partially inhibited the decrease in skeletal muscle cross-sectional area.

Conclusions

Betulinic acid alleviated muscle atrophy in the cast model of muscle atrophy and has therapeutic potential for the treatment of immobilized disuse skeletal muscle atrophy.

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