Frontiers in pharmacology · 2026
Ginsenoside Rb1 ameliorates stress urinary incontinence by upregulating SIRT1 to preserve mitochondrial homeostasis and MAM integrity.
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Chen Liying, Li Lingyun, Chen Mao, Xiao Ya, Li Hanyue, Tian Xiaoyu, Hong Li, Tang Jianming
Аннотация
INTRODUCTION: Stress urinary incontinence (SUI) is a prevalent pelvic floor disorder characterized by impaired connective tissue integrity. Oxidative stress-induced mitochondrial dysfunction has been implicated in pelvic floor degeneration. Ginsenoside Rb1 (Rb1), a bioactive component of ginseng, exhibits antioxidant properties; however, its therapeutic effects and underlying mechanisms in SUI remain unclear.
METHODS: A vaginal distension (VD)-induced mouse model of SUI and an H2O2-induced oxidative stress model in L929 cells were established to investigate the effects of Rb1. Urodynamic evaluation, histological analysis, mitochondrial functional assays, and SIRT1 inhibition/knockdown experiments were performed to explore the molecular mechanisms.
RESULTS: Rb1 significantly improved bladder leak point pressure, preserved collagen organization, and reduced apoptosis in the anterior vaginal wall of VD mice. Rb1 alleviated oxidative stress by reducing ROS accumulation and restoring mitochondrial homeostasis. Mechanistically, Rb1 upregulated SIRT1 and enhanced mitochondrial biogenesis-associated signaling through the PGC-1α/NRF1/TFAM pathway, while promoting PINK1/Parkin-associated mitophagic signaling. Furthermore, Rb1 maintained mitochondria-associated membrane (MAM) integrity by regulating GRP75 acetylation, thereby reducing excessive ER-mitochondrial calcium transfer, mitochondrial calcium overload, and mtROS accumulation. SIRT1 inhibition or knockdown attenuated these protective effects.
CONCLUSION: Ginsenoside Rb1 protects against SUI by promoting SIRT1-associated mitochondrial quality control and preserving MAM homeostasis through regulation of GRP75 acetylation. These findings identify the SIRT1-GRP75/MAM axis as a potential therapeutic target for preventing oxidative stress-induced pelvic floor tissue dysfunction.
METHODS: A vaginal distension (VD)-induced mouse model of SUI and an H2O2-induced oxidative stress model in L929 cells were established to investigate the effects of Rb1. Urodynamic evaluation, histological analysis, mitochondrial functional assays, and SIRT1 inhibition/knockdown experiments were performed to explore the molecular mechanisms.
RESULTS: Rb1 significantly improved bladder leak point pressure, preserved collagen organization, and reduced apoptosis in the anterior vaginal wall of VD mice. Rb1 alleviated oxidative stress by reducing ROS accumulation and restoring mitochondrial homeostasis. Mechanistically, Rb1 upregulated SIRT1 and enhanced mitochondrial biogenesis-associated signaling through the PGC-1α/NRF1/TFAM pathway, while promoting PINK1/Parkin-associated mitophagic signaling. Furthermore, Rb1 maintained mitochondria-associated membrane (MAM) integrity by regulating GRP75 acetylation, thereby reducing excessive ER-mitochondrial calcium transfer, mitochondrial calcium overload, and mtROS accumulation. SIRT1 inhibition or knockdown attenuated these protective effects.
CONCLUSION: Ginsenoside Rb1 protects against SUI by promoting SIRT1-associated mitochondrial quality control and preserving MAM homeostasis through regulation of GRP75 acetylation. These findings identify the SIRT1-GRP75/MAM axis as a potential therapeutic target for preventing oxidative stress-induced pelvic floor tissue dysfunction.