Juyuanjian通过Akt/FoxO1和SIRT1/PGC-1α通路的双重调节，减轻肌肉减少症

Abstract

Background Sarcopenia, an age-related degenerative disease, corresponds to “Qi Xu” syndrome in traditional Chinese medicine. Juyuanjian (JYJ), a classical Qi-tonifying formula, has shown potential against muscle atrophy and functional decline, but its molecular mechanisms are not well understood. Purpose : To investigate whether JYJ protects against sarcopenia and to elucidate its underlying mechanisms. Study Design : Caenorhabditis elegans ( C. elegans ) RW1596, C2C12 myotube cells and senescence-accelerated mouse prone 8 (SAMP8) transgenic mice were used to explore the alleviative effect of JYJ on sarcopenia and the molecular mechanism in vivo and in vitro . Methods : This study systematically evaluated the therapeutic effects of JYJ using multiple biological models. Ultra-high performance liquid chromatography-high-resolution mass spectrometry (UPLC-MS) was employed to characterize its chemical constituents, followed by network pharmacology to predict potential targets and pathways. These mechanisms were further validated through molecular biology experiments. Additionally, molecular docking and molecular dynamics simulations were conducted to elucidate the interactions and binding stability between key bioactive components and target proteins. Results : JYJ significantly alleviated muscle fiber damage in C. elegans RW1596 and mitigated the decline in skeletal muscle mass and strength in SAMP8 mice. Furthermore, JYJ inhibited chronic low-grade inflammation by reducing tumor necrosis factor-α (TNF-α) and interleukin-6(IL-6) levels, decreasing macrophage infiltration, and suppressing nuclear factor-kappa B (NF-κB) activation. Network pharmacology analysis indicated that mitochondrial biogenesis and proteasome-mediated ubiquitin-dependent processes were the main biological processes, with protein kinase B (Akt), forkhead box O1 (FoxO1), sirtuin 1 (SIRT1), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) as key targets. Cons