Stem cell research & therapy · 2026
Awakening endogenous repair: salidroside boosts mitophagy in NPMSCs via SIRT1/FOXO3 to combat intervertebral disc degeneration.
СтатьяНазвание и аннотация: Перевод в очереди
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Li Zhengguang, Wu Yiming, Hua Benkui, Sun Hua, Wu Huofeng, Zai Shuangjia, Liu Chen, Zhang Yongbo, Li Zhaoyu, You Xuan, Huang Yufeng, Lu Xuhua, Yin Guoyong, Zhang Liang
Аннотация
BACKGROUND: Intervertebral disc degeneration (IVDD) is a major cause of low back pain, characterized by mitochondrial dysfunction and impaired mitophagy in nucleus pulposus-derived mesenchymal stem cells (NPMSCs). Sirtuin 1 (SIRT1), a key regulator of mitochondrial quality control, is downregulated in degenerated discs. Salidroside (Sal), a natural compound from Rhodiola rosea, has shown potential in enhancing mitophagy, but its mechanism in IVDD remains unclear.
METHODS: Using network pharmacology, molecular docking, and dynamics simulations, we identified SIRT1 as a key target of Sal. Human and rat NPMSCs were isolated and treated with tert-butyl hydroperoxide (TBHP) to induce degeneration. In vitro assays included CCK-8, EdU, SA-β-Gal, JC-1, Western blot, immunofluorescence, and transmission electron microscope (TEM). An in vivo rat IVDD model was established via needle puncture and treated with Sal and/or the autophagy inhibitor 3-MA. Histological, immunohistochemical, and imaging analyses were performed to evaluate IVDD.
RESULTS: Sal bound stably to SIRT1 and activated SIRT1/FOXO3 pathway, promoting mitophagic flux, reducing reactive oxygen species accumulation, and suppressing apoptosis in NPMSCs. SIRT1 knockdown or 3-MA treatment abolished Sal's protective effects. In vivo, Sal treatment preserved disc height, reduced apoptosis, and enhanced mitophagy, while 3-MA exacerbated degeneration.
CONCLUSIONS: Sal attenuates IVDD by activating SIRT1/FOXO3-mediated mitophagy, restoring mitochondrial homeostasis, and reducing NPMSCs apoptosis. These results suggest that the activation of the SIRT1/FOXO3-mitophagy axis may represent a potential therapeutic strategy for mitigating IVDD.
METHODS: Using network pharmacology, molecular docking, and dynamics simulations, we identified SIRT1 as a key target of Sal. Human and rat NPMSCs were isolated and treated with tert-butyl hydroperoxide (TBHP) to induce degeneration. In vitro assays included CCK-8, EdU, SA-β-Gal, JC-1, Western blot, immunofluorescence, and transmission electron microscope (TEM). An in vivo rat IVDD model was established via needle puncture and treated with Sal and/or the autophagy inhibitor 3-MA. Histological, immunohistochemical, and imaging analyses were performed to evaluate IVDD.
RESULTS: Sal bound stably to SIRT1 and activated SIRT1/FOXO3 pathway, promoting mitophagic flux, reducing reactive oxygen species accumulation, and suppressing apoptosis in NPMSCs. SIRT1 knockdown or 3-MA treatment abolished Sal's protective effects. In vivo, Sal treatment preserved disc height, reduced apoptosis, and enhanced mitophagy, while 3-MA exacerbated degeneration.
CONCLUSIONS: Sal attenuates IVDD by activating SIRT1/FOXO3-mediated mitophagy, restoring mitochondrial homeostasis, and reducing NPMSCs apoptosis. These results suggest that the activation of the SIRT1/FOXO3-mitophagy axis may represent a potential therapeutic strategy for mitigating IVDD.