In traditional Chinese medicine, ginsenoside Rb1 (Rb1) is a major active ingredient from ginseng known for its capacity to alleviate oxidative stress, regulate autophagy, and suppress apoptosis. However, its potential influence on the natural aging process has not been fully explored. To examine the effects of Rb1 on natural aging and to uncover the possible underlying molecular mechanisms. Middle-aged (12-month-old) and aged (20-month-old) mice were treated with Rb1 at low (10 mg/kg·d) or high (20 mg/kg·d) doses for eight consecutive weeks. Changes in body weight and spatial learning ability were monitored in relation to aging manifestations. Oxidative stress indicators and nitric oxide (NO) concentrations were measured in hippocampal tissue following treatment, along with evaluation of aging-related biomarkers and associated pathways. Rb1 administration markedly mitigated several physiological signs of aging, such as slowing body weight decline, preventing the deterioration of visuospatial learning and memory, and reducing senescence in brain tissues. Mice receiving Rb1 showed lower serum malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) activity, and decreased production of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Moreover, Rb1 elevated serum NO levels and enhanced Sirtuin 1 (SIRT1) protein expression, indicating that its anti-aging actions are closely linked to modulation of the SIRT1/eNOS/NO signaling axis. Rb1 delays aging progression in mice by regulating the SIRT1/eNOS/NO pathway, which helps reduce oxidative stress and inflammatory responses.
