Centella asiatica attenuates hippocampal mitochondrial dysfunction and improves memory and executive function in...

Area of Science:

• Neuroscience
• Pharmacology
• Biochemistry

Background:

• Centella asiatica is a medicinal herb traditionally used for memory enhancement.
• Previous studies demonstrated that Centella asiatica water extract (CAW) mitigates spatial memory deficits and improves neuronal health in mice with beta-amyloid (Aβ) accumulation.
• The effects of CAW on broader cognitive functions and its in vivo mechanisms against Aβ-related cognitive impairment remain largely unexplored.

Purpose of the Study:

• To investigate the effects of CAW on learning, memory, and executive function in the 5xFAD mouse model of Aβ accumulation.
• To explore the impact of CAW on mitochondrial function and antioxidant responses in vivo.
• To elucidate the underlying mechanisms by which CAW ameliorates Aβ-related cognitive impairment.

Main Methods:

• Seven-month-old 5xFAD female mice received CAW (2 mg/mL) in their drinking water for two weeks.
• Cognitive functions were assessed using the object location memory (OLM), conditioned fear response (CFR), and odor discrimination reversal learning (ODRL) tests.
• Mitochondrial function was analyzed using the Seahorse XF platform, and hippocampal and cortical tissues were examined for protein and gene expression related to mitochondria, antioxidants, and synapses.

Main Results:

• CAW treatment significantly improved performance in all behavioral tests (OLM, CFR, ODRL) in 5xFAD mice, with no effect observed in wild-type (WT) animals.
• CAW administration enhanced hippocampal mitochondrial function and increased the expression of mitochondrial genes in the hippocampus and cortex of 5xFAD mice.
• CAW treatment upregulated the transcription factor NRF2 and its antioxidant target enzymes in both WT and 5xFAD mice, and reduced hippocampal Aβ-plaque burden in 5xFAD mice.

Conclusions:

• Centella asiatica water extract (CAW) effectively improves multiple cognitive domains, including learning, memory, and executive function, in a mouse model of Alzheimer's disease.
• CAW administration attenuates hippocampal mitochondrial dysfunction and enhances the antioxidant response, partly through NRF2 activation.
• The findings suggest that CAW has potentially broad therapeutic applications for cognitive impairments associated with mitochondrial dysfunction and oxidative stress, extending beyond Alzheimer's disease.