Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026
Juyuanjian attenuates sarcopenia through dual regulation of the Akt/FoxO1 and SIRT1/PGC-1α pathways.
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Yan Yibing, Liu Xihong, Zhao Peiyuan, Zhang Xiaowei, Ma Huifen, Cao Bing, Yang Peiyan, Gao Gai, Xie Zhishen, Zhang Zhenqiang
Аннотация
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 (MD) 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. Consistent with this, JYJ enhanced the phosphorylation of Akt and FoxO1 both in vitro and in vivo, while downregulating the expression of muscle atrophy-related E3 ubiquitin ligases muscle ring finger 1 (MuRF1) and muscle atrophy F-box (MAFbx); it also upregulated the expression of SIRT1 and PGC-1α, promoting mitochondrial biogenesis and adenosine triphosphate (ATP) production. Molecular docking and 100-nanosecond MD simulations showed stable interactions between the bioactive components of JYJ and Akt/SIRT1, supported by favorable binding free energy and stable conformational dynamics.
CONCLUSIONS: JYJ exerts anti-sarcopenic effects by dual regulation of protein degradation (Akt/FoxO1) and mitochondrial biogenesis (SIRT1/PGC-1α), providing a phytotherapeutic for sarcopenia.
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 (MD) 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. Consistent with this, JYJ enhanced the phosphorylation of Akt and FoxO1 both in vitro and in vivo, while downregulating the expression of muscle atrophy-related E3 ubiquitin ligases muscle ring finger 1 (MuRF1) and muscle atrophy F-box (MAFbx); it also upregulated the expression of SIRT1 and PGC-1α, promoting mitochondrial biogenesis and adenosine triphosphate (ATP) production. Molecular docking and 100-nanosecond MD simulations showed stable interactions between the bioactive components of JYJ and Akt/SIRT1, supported by favorable binding free energy and stable conformational dynamics.
CONCLUSIONS: JYJ exerts anti-sarcopenic effects by dual regulation of protein degradation (Akt/FoxO1) and mitochondrial biogenesis (SIRT1/PGC-1α), providing a phytotherapeutic for sarcopenia.