Ginsenoside Rb1 attenuates age-associated cognitive impairment by modulating oxidative stress and the SIRT1/eNOS/NO axis.

Background: In traditional Chinese medicine ginseng, ginsenoside Rb1 (Rb1) is an active compound that has been shown to alleviate oxidative stress, modulate autophagy, and inhibit apoptosis. However, its role in the natural aging process remains unknown. Aim: Investigate the role of Rb1 in natural aging and potential molecular mechanisms. Methods: During eight weeks of treatment with Rb1, we administered low-dose (10 mg/kg·d) or high-dose (20 mg/kg·d) Rb1 to middle-aged (12-month-old) and aged (20-month-old) mice, and observed how changes in body weight and spatial learning were related to aging symptoms. Further, we measured oxidative stress-related markers and nitric oxide (NO) levels in the mice's hippocampal tissue after Rb1 treatment, and identified aging-related biomarkers and pathways. Results: Treatment with Rb1 greatly reduced the physiological changes associated with aging, such as the weight loss slowing, the inhibition of the loss of visuospatial learning and memory ability, and the senescence of brain tissues. Mice treated with Rb1 had lower serum levels of malondialdehyde (MDA) and higher superoxide dismutase (SOD) activity, along with a reduction in the release of pro-inflammatory markers such tumor necrosis factor-α (TNF-α) and Interleukin-6 (IL-6). Furthermore, Rb1 therapy raised serum NO levels and improved Sirtuin 1 (SIRT1) protein expression, indicating that its anti-aging benefits are connected to the control of the SIRT1/eNOS/NO axis. Conclusions: Rb1 modulates the SIRT1/eNOS/NO axis, which is linked to reducing oxidative stress and inflammatory reactions, hence delaying the aging process in mice.