Jin Hengzhe, Seo Hyoung Sig, Shin Jinyoung, Lee Kyung-Jin, Kim Su Jung, Jung Seung Hyo, Kim Bokyung
Department of Physiology, School of Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, South Korea.
Research Institute of KSB TUGEN Inc., Gwangjin-gu, Seoul, 05029, South Korea.
Eur J Pharmacol. 2025 Mar 5;990:177265. doi: 10.1016/j.ejphar.2025.177265. Epub 2025 Jan 10.
Andrographis paniculata (AGPA) is known for its wide-ranging biological activities, including antiviral, antipyretic, and anticancer properties. However, its effects on muscle atrophy have not been well understood. This study investigates the impact of andrographolide (AD) and dehydroandrographolide succinate (DAS), key components of AGPA, on skeletal muscle atrophy using in vitro and in vivo models. We employed dexamethasone (DEX)-treated mice and C2C12 myotubes as models of skeletal muscle atrophy. While DAS and AD did not reverse the DEX-induced reduction in body weight, both compounds significantly restored grip strength in DEX-treated mice. Notably, DAS treatment, but not AD, markedly improved running speed, endurance time, and distance. Both DAS and AD enhanced lean muscle mass in the whole body, tibialis anterior (TA), and gastrocnemius (GS) muscles, as well as increased TA thickness, with DAS demonstrating superior efficacy compared to AD. In C2C12 myotubes treated with DEX, DAS and AD increased ATP production and myotube diameter. Mechanistically, both compounds upregulated phosphorylation of Akt and GSK3β and downregulated MuRF-1 expression. These results indicate that DAS and AD mitigate muscle atrophy via the Akt/GSK3β and MuRF-1 pathways, with DAS showing greater anti-atrophy efficiency. Thus, DAS emerges as a promising therapeutic candidate for the prevention of skeletal muscle atrophy.
穿心莲（AGPA）以其广泛的生物活性而闻名，包括抗病毒、解热和抗癌特性。然而，其对肌肉萎缩的影响尚未得到充分了解。本研究使用体外和体内模型，研究穿心莲内酯（AD）和脱水穿心莲内酯琥珀酸半酯（DAS）这两种AGPA的关键成分对骨骼肌萎缩的影响。我们采用地塞米松（DEX）处理的小鼠和C2C12肌管作为骨骼肌萎缩模型。虽然DAS和AD并未逆转DEX诱导的体重减轻，但这两种化合物均显著恢复了DEX处理小鼠的握力。值得注意的是，DAS处理而非AD处理显著提高了跑步速度、耐力时间和距离。DAS和AD均增加了全身、胫前肌（TA）和腓肠肌（GS）的瘦肌肉质量，以及增加了TA的厚度，与AD相比，DAS显示出更高的疗效。在用DEX处理的C2C12肌管中，DAS和AD增加了ATP生成和肌管直径。从机制上讲，这两种化合物均上调了Akt和GSK3β的磷酸化，并下调了MuRF-1的表达。这些结果表明，DAS和AD通过Akt/GSK3β和MuRF-1途径减轻肌肉萎缩，其中DAS显示出更高的抗萎缩效率。因此，DAS有望成为预防骨骼肌萎缩的治疗候选药物。
