Laboratory of Traditional Chinese Medicine Research and Development of Hebei Province, Institute of Traditional Chinese Medicine, Chengde Medical University, Chengde 067000, China.
Department of Pathogen Biology, Chengde Medical University, Chengde 067000, China.
Molecules. 2024 Sep 19;29(18):4448. doi: 10.3390/molecules29184448.
Compound was previously identified by our team as a glycogen phosphorylase (GP) inhibitor with glucose-lowering activity and demonstrated to have protective effects against myocardial and cerebral ischemia. However, its impact on muscle function has not been clarified. This study is the first to evaluate the long-term effects of GP inhibitors on muscle function and metabolism. After a 28-day administration of Compound , we performed assays to assess muscle function and biochemical parameters in rats. We observed reductions in peak holding force, duration, tetanic contraction force, single-contraction force, and electromyographic signals under 20 s and 10 min contraction stimuli. The metabolic analysis showed no significant effects on muscle glycogen, ATP, lactic acid, and uric acid levels at low doses. In contrast, medium to high doses resulted in increased glycogen, decreased ATP, and reduced lactic acid (only at high doses), without affecting uric acid. These findings suggest that Compound may adversely affect muscle function in rats, potentially due to the glycogen inhibition effects of GP inhibitors. This study provides crucial safety data and insights into the long-term effects of GP inhibitors on rat muscles, which will guide future developments and applications.
该化合物先前由我们的团队鉴定为一种糖原磷酸化酶 (GP) 抑制剂，具有降低血糖的活性，并已被证明对心肌和脑缺血具有保护作用。然而，其对肌肉功能的影响尚未阐明。本研究首次评估了 GP 抑制剂对肌肉功能和代谢的长期影响。在给予化合物 28 天后，我们对大鼠进行了肌肉功能和生化参数的检测。我们观察到在 20 秒和 10 分钟收缩刺激下，峰值保持力、持续时间、强直收缩力、单次收缩力和肌电图信号降低。代谢分析显示低剂量对肌肉糖原、ATP、乳酸和尿酸水平没有显著影响。相比之下，中高剂量导致糖原增加，ATP 减少，乳酸减少（仅在高剂量时），尿酸不受影响。这些发现表明，化合物可能会对大鼠的肌肉功能产生不利影响，这可能是由于 GP 抑制剂对糖原的抑制作用。本研究为 GP 抑制剂对大鼠肌肉的长期影响提供了关键的安全性数据和见解，将指导未来的开发和应用。
