Ginsenoside Rg1 enhances stem cell abundance in aging human skeletal muscle after resistance exercise

BACKGROUND: Ginsenoside Rg1 enhances senolytic effect of exercise in human skeletal muscle. PURPOSE: To determine the effects of Rg1 on stem cell enrichment and differentiation in skeletal muscle following resistance exercise in women over 60. METHODS: In a randomized, double-blind, placebo-controlled crossover trial, 11 women (60-73 years) completed four sets of seated leg press (70% 1RM) 1 h after ingesting Placebo or Rg1 (10 mg). Muscle biopsies were assessed for activated mesenchymal stem cells (Stro-1⁺/Tom20high), neural progenitors (Nestin⁺), and vascular progenitors (CD34⁺/CD31⁺) at 0 h and 24 h post-exercise. RESULTS: While exercise alone did not alter Stro-1⁺ cells and mitochondrial content (TOM20⁺) in muscle tissues, the high mitochondrial Stro-1⁺ cells was decreased by 45% (p < 0.05). Rg1 supplementation doubled high mitochondrial Stro-1⁺ cells and total mitochondrial content post-exercise (p < 0.05). Concentration gradient between the Stro-1⁺ cells and engaged myofibers is consistent with a potential mitochondrial delivery mechanism from bone marrow stem cells. Exercise reduced CD34⁺ cells (-68%, p < 0.05) and Nestin⁺ neural progenitors (-50%, p < 0.05), whereas Rg1 attenuated CD34⁺ cell depletion and increased Nestin⁺ neural progenitors by twofold (p < 0.05). Vascular endothelial progenitors (CD34⁺/CD31⁺) remained unchanged after exercise. Exercise decreased serum estradiol levels (-43%, p < 0.05), whereas Rg1 supplementation restored estradiol to pre-exercise levels and doubled progesterone concentrations. CONCLUSION: Rg1 supplementation prevents exercise-induced sex steroid depletion and markedly enhances stem cell abundance in skeletal muscle, which contributes to mitochondrial gains following resistance exercise in women over 60.