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

Journal of Ginseng Research

Available online 26 June 2025

Journal of Ginseng ResearchAuthor links open overlay panel, , , , , , , , , , , , Highlights•

Rb 1 may ameliorate aging-associated cognitive decline.

Rb 1 can reduce oxidative stress and inflammation in senescent cells and brain tissue in middle-aged and aged mice.

The SIRT 1 / eNOS axis has an important role in the anti-aging effects of Rb 1.

Rb1 can delay age-related cellular aging by inhibiting inflammation and regulating the SIRT1/eNOS signaling pathway in vivo.

AbstractBackground

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 used metabolomics analysis to investigate aging-related metabolite changes in the mice's hippocampal tissue after Rb1 treatment and detected 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 Nitric oxide (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 inhibits the SIRT1/eNOS/NO axis, which is linked to reducing oxidative stress and inflammatory reactions, hence delaying the aging process in mice.

Graphical abstractImage 1Download: Download high-res image (241KB)Download: Download full-size imageKey words

Ginsenoside Rb1

Aged mice

cognitive impairment

oxidative stress

SIRT1/eNOS/NO axis

© 2025 The Korean Society of Ginseng. Publishing services by Elsevier B.V.

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