Polygonatum polysaccharide improves cognitive function in senescence-accelerated mice by regulating ferroptosis...

Area of Science:

• Neuroscience
• Pharmacology
• Aging Research

Background:

• Cognitive decline is a hallmark of aging and neurodegenerative diseases.
• Polygonatum odoratum, a traditional Chinese medicine, contains Polygonatum polysaccharide (POP), known for antioxidant and anti-aging properties.
• Neuronal ferroptosis is implicated in cognitive impairment, presenting a therapeutic target.

Purpose of the Study:

• To investigate the mechanism by which POP inhibits ferroptosis and improves cognitive function.
• To elucidate POP's role in the cAMP/PKA/CREB signaling pathway in rapidly aging mice.

Main Methods:

• Administration of POP to 6-month-old SAMP8 mice.
• Assessment of cognitive function using the water maze.
• Histopathological analysis, transcriptomics, and in vivo experiments to validate the mechanism.

Main Results:

• POP significantly improved cognitive function in SAMP8 mice, reducing latency and increasing target quadrant dwell time.
• POP decreased Acsl4 expression and increased Slc7A11 expression, key markers in ferroptosis.
• POP activated the cAMP/PKA/CREB pathway, reducing Fe2+ and MDA, and increasing GSH and SOD, thereby inhibiting ferroptosis.

Conclusions:

• POP ameliorates age-related cognitive decline in SAMP8 mice.
• The mechanism involves POP-mediated inhibition of ferroptosis through the cAMP/PKA/CREB pathway.
• POP demonstrates potential as a therapeutic agent for cognitive impairment.