Zhang Yunxia, Wu Xiaoxiao, Li Ruoqi, Sui Mengru, Li Guoyin, Fan Shuhua, Yang Mingsheng, Liu Qiuping, Liu Xiaomeng, Wu Changjing, Li Lili
Institute of Translational Medicine, College of Life Science and Agronomy, Zhoukou Normal University, Zhoukou, Henan, China.
Dancheng Green Agriculture Observation and Research Station of Henan Province, Zhoukou Normal University, Zhoukou, China.
Front Pharmacol. 2024 Oct 22;15:1467620. doi: 10.3389/fphar.2024.1467620. eCollection 2024.
Sodium Danshensu (SDSS) is extracted from and has many pharmacological effects. However, little is known about its effects on muscle fiber formation and metabolism. Here, we aimed to investigated the role and molecular mechanisms of SDSS in modulating the formation of skeletal muscle fiber. C2C12 cells were incubated in differentiation medium with or without SDSS for 4 days. C57BL/6 mice were orally administered SDSS by gavage once a day for 8 weeks. Grip strength, treadmill, muscle weight, western blotting, qPCR, immunofluorescence staining and H&E staining were performed. SDSS target proteins were searched through drug affinity responsive target stability (DARTS) and mass spectrometry analysis. Furthermore, molecular docking was carried out for Pyruvate kinase M1 (PKM1). The effect of PKM1 on myosin heavy chain () gene expression was verified by knockdown of PKM1 experiment. SDSS induced oxidative muscle fiber-related gene expression, and inhibited glycolytic fiber-related gene expression in C2C12 cells. Muscle mass, the percentage of slow oxidative fibers, succinic dehydrogenase activity, muscle endurance, glucose tolerance, and the expression of the and genes increased while expression, lactate dehydrogenase activity, and the percentage of glycolytic muscle fibers decreased in SDSS-treated mice. Mechanistically, SDSS bound to the pyruvate kinase PKM1 and significantly repressed its activity. PKM1 inhibited C1 and a expression but promoted expression. SDSS also significantly attenuated the effects of PKM1 on muscle fiber-related gene expression in C2C12 cells. Our findings indicate that SDSS promotes muscle fiber transformation from the glycolytic type to the oxidative type by inhibiting PKM1 activity, which provide a new idea for treating muscle atrophy, muscle metabolism diseases and improving animal meat production.
丹参素钠（SDSS）是从[具体来源未提及]中提取的，具有多种药理作用。然而，其对肌纤维形成和代谢的影响却知之甚少。在此，我们旨在研究SDSS在调节骨骼肌纤维形成中的作用及分子机制。将C2C12细胞在含或不含SDSS的分化培养基中培养4天。C57BL/6小鼠每天经口灌胃给予SDSS，持续8周。进行握力、跑步机运动测试、肌肉重量测量、蛋白质免疫印迹法、定量聚合酶链反应、免疫荧光染色和苏木精-伊红染色。通过药物亲和反应靶点稳定性（DARTS）和质谱分析寻找SDSS的靶蛋白。此外，对丙酮酸激酶M1（PKM1）进行分子对接。通过PKM1基因敲低实验验证PKM1对肌球蛋白重链（[具体基因未提及]）基因表达的影响。SDSS诱导C2C12细胞中氧化型肌纤维相关基因表达，并抑制糖酵解型纤维相关基因表达。在经SDSS处理的小鼠中，肌肉质量、慢氧化型纤维百分比、琥珀酸脱氢酶活性、肌肉耐力、葡萄糖耐量以及[具体基因未提及]和[具体基因未提及]基因的表达增加，而[具体基因未提及]表达、乳酸脱氢酶活性和糖酵解型肌纤维百分比降低。机制上，SDSS与丙酮酸激酶PKM1结合并显著抑制其活性。PKM1抑制[具体基因未提及]和[具体基因未提及]表达，但促进[具体基因未提及]表达。SDSS还显著减弱了PKM1对C2C12细胞中肌纤维相关基因表达的影响。我们的研究结果表明，SDSS通过抑制PKM1活性促进肌纤维从糖酵解型向氧化型转变，这为治疗肌肉萎缩、肌肉代谢疾病以及提高动物肉产量提供了新思路。
