Damage-induced muscle regeneration after exercise in humans: Modulatory effects of ginsenoside Rg1

Exercise-induced focal sarcolemmal disruption in susceptible myofibers results in bone marrow cell infiltration and reduced cellular senescence in skeletal muscle, followed by increases in muscle strength and mass. In contrast, removal of gravitational loading during spaceflight or prolonged bed rest leads to rapid losses of muscle mass and strength, recapitulating features of ageing. Accumulating evidence indicates that this exercise-induced muscle adaptation is driven by damage-evoked immune signaling that mobilizes bone marrow-derived progenitor cells to sites of tissue injury for regeneration. Cross-age transplantation studies further demonstrate that circulating bone marrow-derived cells (i.e., immune and progenitor cells) are key determinants of muscle regenerative capacity. Recent human muscle biopsy studies reveal that infiltrating immune and progenitor cells can fuse with damaged myofibers and contribute mitochondria during recovery. Within this damage-induced regeneration framework, ginsenosides, the bioactive steroidal constituents of Panax species, have emerged as potential modulators of immune activation, stem/progenitor cell mobilization, and cell-state regulation. However, randomized controlled trials using different ginseng extracts have yielded inconsistent outcomes in exercise adaptation, likely due to variability in ginsenoside composition across species, cultivation season, and processing. To date, rigorously controlled, double-blind trials using standardized ginsenoside remain scarce. Rg1 is the only compound supported by human biopsy evidence, associated with reproducible reductions in perceived exertion and senolytic effects following exercise-induced muscle damage. This review reports current evidence on ginsenosides, with a specific focus on Rg1, within an attrition-regeneration framework and proposes a testable mechanistic model to guide future human trials and translation.