Ginsenoside Rb1 Ameliorates Age-Related Cognitive Impairment Potentially by Modulating the NF-κB Signaling Pathway

Age-related cognitive impairment affects the quality of life of the elderly, contributing to a substantial healthcare burden. Ginsenoside Rb1 (Rb1), an active component of ginseng, has been shown to possess various biological functions, including antisenescence, anti-inflammatory, and neuroprotection effects. This study investigated whether Rb1 attenuates age-related cognitive impairment and aimed to elucidate the relevant molecular mechanism.

Female C57BL/6J mice (aged 2 and 18 months) received daily intraperitioneal injections of either Rb1 or vehicle for 3 months. Subsequently, their cognitive ability was assessed using the Morris water maze (MWM) test. Pathological changes in hippocampal neurons were investigated using hematoxylin and eosin (HE) staining and Nissl staining. In addition, Western blot and immunohistochemistry were employed to examine proteins relevant to cellular senescence (cyclin-dependent kinase inhibitor 1A [p21^Cip1] and cyclin-dependent kinase inhibitor 2A‌ [p16^INK4a]), inflammation (interleukin-6 [IL-6] and tumor necrosis factor-α [TNF-α]), and markers indicating nuclear factor-kappa B (NF-κB) pathway activation in hippocampus tissue.

In the MWM test, Rb1 treatment significantly ameliorated cognitive dysfunction in aging mice compared to controls. Results from HE staining and Nissl staining showed marked neuronal loss, neurodegeneration, and uneven cytoplasm distribution of Nissl bodies in the hippocampus of aging mice, all of which were alleviated by Rb1 treatment. Immunohistochemistry and Western blot analyses demonstrated a pronounced increase in p21^Cip1, ‌p16^INK4a, IL-6, and TNF-α expression levels in the CA1 and CA3 regions of the hippocampus, along with enhanced phosphorylation of NF-κB, inhibitor of NF-κB (IκB) kinase (IKKβ) and IκBα in the aging mice. However, Rb1 treatment significantly downregulated p21^Cip1, p16^INK4a, IL-6, and TNF-α expression levels, indicating that Rb1 alleviated cellular senescence and neuroinflammation in the hippocampus. Furthermore, Rb1 administration evidently repressed the phosphorylation of NF-κB, IKKβ, and IκBα in the aging mice.

Rb1 may alleviate aging-related cognitive impairment by suppressing hippocampal inflammation, potentially through modulation of the NF-κB signaling pathway.