Byun Mi Ran, Kim Sou Hyun, Woo RanJu, Noh Seung Jun, Joo Sang Hoon, Jung Young-Suk, Choi Joon-Seok
Department of Pharmacy, Daegu Catholic University, 13-13 Hayang-ro, Hayang-eup, Gyeongsan-Si, Gyeongbuk 38430 Republic of Korea.
Department of Pharmacy, College of Pharmacy, Research Institute for Drug Development, Pusan National University, Busan, 46241 Republic of Korea.
Toxicol Res. 2024 Dec 13;41(1):81-90. doi: 10.1007/s43188-024-00273-w. eCollection 2025 Jan.
Sarcopenia is a disease characterized by decreased muscle fibers and mass. Although it mainly affects the older adults, it can also occur in various age groups as a secondary effect of medications used for treating certain diseases, such as cancer and diabetes. With population aging, sarcopenia has drawn significant attention owing to its increasing prevalence. However, its pathogenesis remains unclear, and no specific treatment is available. Natural products containing bioactive compounds have long been used as therapeutic agents and are crucial sources for drug development. However, the use of drugs derived from natural extracts is limited because of their ambiguous mechanisms of action and potential side effects. Therefore, a systematic analysis of the potential effects of using natural products is required. In this study, we investigated the effects of the antimalarial drug quinine on myogenic differentiation. Our findings revealed that quinine significantly inhibited the expression of marker genes and proteins associated with myogenic differentiation and markedly impaired muscle regeneration following injury. Furthermore, this reduction occurred when quinine selectively decreased the AKT signaling activity. Quinine reduced muscle protein and gene expression by modulating AKT signaling and inhibiting myogenic differentiation and muscle regeneration. Therefore, quinine may cause sarcopenia, and this risk should be considered when using quinine for treatment.
肌肉减少症是一种以肌纤维和肌肉质量减少为特征的疾病。虽然它主要影响老年人，但作为用于治疗某些疾病（如癌症和糖尿病）的药物的次要作用，它也可能发生在各个年龄组。随着人口老龄化，肌肉减少症因其患病率不断上升而备受关注。然而，其发病机制仍不清楚，且尚无特效治疗方法。含有生物活性化合物的天然产物长期以来一直被用作治疗药物，并且是药物开发的重要来源。然而，由于其作用机制不明确和潜在的副作用，源自天然提取物的药物的使用受到限制。因此，需要对使用天然产物的潜在影响进行系统分析。在本研究中，我们研究了抗疟药物奎宁对肌生成分化的影响。我们的研究结果表明，奎宁显著抑制与肌生成分化相关的标记基因和蛋白质的表达，并显著损害损伤后的肌肉再生。此外，当奎宁选择性降低AKT信号活性时，这种减少就会发生。奎宁通过调节AKT信号传导、抑制肌生成分化和肌肉再生来降低肌肉蛋白质和基因表达。因此，奎宁可能会导致肌肉减少症，在使用奎宁进行治疗时应考虑这种风险。
