Preclinical study shows aged garlic extract improves memory and reduces anxiety

By Priyanjana Pramanik, MSc.Reviewed by Susha Cheriyedath, M.Sc.Nov 16 2025

New findings show that aged garlic extract reshapes brain pathways tied to memory and emotion, revealing a promising multi-target strategy for supporting cognitive resilience as the brain ages.

Study: Supplementation of aged garlic extract attenuates age-associated memory impairment and cognitive decline: Involvement of molecular pathways in the cortex and hippocampus. Image Credit: New Africa / Shutterstock

In a recent study in the journal Biomedical Reports, researchers at the University of Missouri investigated whether consuming aged garlic extract can improve long-term behavioral and cognitive outcomes in mice.

They found that supplementing mice diets with aged garlic extract produced significant changes in the hippocampus and measurable though smaller changes in the cortex, and improved anxiety-related responses, exploratory behavior, memory, and learning.

The authors note that while these findings are promising, translation to human therapies remains uncertain and requires further research.

Neurobiological Risks in Aging Populations

The aging adult population in the United States is experiencing rising rates of comorbidities closely tied to age-related brain changes. Aging is associated with reduced volumes in regions such as the frontal lobe and hippocampus, increased reactive oxygen species, myelin deterioration, mitochondrial dysfunction, and calcium imbalance.

These processes contribute to cognitive decline, sensorimotor impairments, and increased susceptibility to neurodegenerative diseases like Alzheimer’s and Parkinson’s disease. 

However, effective preventive strategies for these conditions remain limited. Because these disorders involve multiple overlapping pathways, holistic or multi-target approaches may hold promise.

Bioactive Properties of Aged Garlic Extract

For centuries, people have utilized garlic for both culinary and medicinal purposes, primarily due to its sulfur-containing compounds. Aged garlic extract is an odorless, stable preparation enriched in bioactive components with established antioxidant and anti-inflammatory properties. 

Extensive research in humans and animals shows that aged garlic extract can improve cardiovascular health, reduce inflammation, enhance arterial elasticity, and slow the progression of atherosclerosis. 

Its components have also been shown to protect against oxidative stress, improve metabolism, and modulate neuroinflammatory pathways. Short-term animal studies suggest that aged garlic extract may enhance learning and memory and reduce neuropathology. 

Building on this evidence, researchers evaluated the long-term molecular and neurological effects of chronic aged garlic extract supplementation during natural aging in mice using a male C57BL/6J cohort and an AIN-93G diet supplemented with 40 percent aqueous aged garlic extract.

Experimental Design Using Long-Term Supplementation

The study used 48 male mice aged 42 weeks, housed under controlled environmental conditions. After a one-week acclimation period, mice were randomly assigned to receive either a standard diet or the same diet supplemented with aged garlic extract for 40 weeks. Food intake and body weight were monitored regularly.

Behavioral Test Battery Assessing Cognition and Anxiety

After the feeding period, mice were transitioned to a reverse light/dark cycle and underwent a comprehensive battery of behavioral tests to assess sensorimotor function, exploratory behavior, anxiety-like responses, sociability, recognition memory, and spatial learning.

These tests included the inverted screen test, the simple neuro-assessment of asymmetric impairment test, light-dark transition test, open-field test, novel object recognition task, emergence test, elevated plus maze, zero maze, Barnes maze, and three-chamber sociability test. Behavioral data were analyzed using analysis of variance or unpaired t-tests.

Proteomics Workflow for Brain-Region Analysis

A subset of ten mice was euthanized for proteomic analyses. Cortical and hippocampal tissues were collected, homogenized, and processed for label-free global proteomics using tandem mass spectrometry.

Proteins were extracted, reduced, alkylated, digested with trypsin, and analyzed to create a spectral library and quantify protein expression. These data were later used for machine-learning-based bioinformatic analyses.

Behavioral Outcomes Showing Reduced Anxiety

Across 40 weeks, aged mice fed aged garlic extract showed no differences in food intake, body weight, mortality, or general health compared with controls. Sensorimotor assessments, including coordination and grip strength, also remained unchanged. However, aged garlic extract supplementation produced clear behavioral benefits in anxiety- and neophobia-related domains.

In the light-dark transition test, supplemented mice entered the dark zone less often and spent more time in the light zone, indicating reduced anxiety. 

Similar reductions in neophobia were observed in the emergence test, where supplemented mice spent less time sheltered, explored the arena more, travelled farther, and were less immobile. 

As reported in the study, no effects were detected in the open field, elevated plus maze, or zero maze.

Cognitive Improvements in Memory and Learning

Cognitive performance improved with the use of aged garlic extract. In the novel object recognition test, supplemented mice showed a higher discrimination index and greater engagement with the novel object, suggesting enhanced learning and recognition memory. 

In the Barnes maze, a larger proportion of supplemented mice located the escape box, and during reversal learning, they showed shorter latencies, particularly early in training. Social interaction measures were unchanged.

Proteomic Signatures in Hippocampus and Cortex

Proteomic analyses revealed substantial changes in protein expression induced by aged garlic extract, especially in the hippocampus, where 336 differentially expressed proteins were identified, and 90 in the cortex. 

Key shared changes included reduced Selenbp1 and increased Pdyn in both brain regions. Pathway modeling predicted effects on synaptic signaling, apoptosis regulation, cognition, memory, and anxiety-related behaviors. 

The authors also identified changes involving tau, amyloid precursor protein, presenilin 1, and brain-derived neurotrophic factor, which may be relevant to neurodegenerative pathways.

Interpretation Supporting Neuroprotective Potential

The study supports the idea that aged garlic extract can counter age-related cognitive decline by mechanisms that are suggested but not definitively demonstrated here, such as antioxidant, anti-inflammatory, and neuroprotective actions, based on prior literature and pathway analyses.

Behavioral improvements in anxiety, memory, and learning are consistent with earlier animal studies and likely reflect modulation of neuroplasticity, stress-response pathways, and apoptosis. 

Proteomic and pathway analyses further suggest region-specific molecular effects, especially within the hippocampus.

Study Strengths and Translational Limitations

Strengths of this analysis include the long supplementation period, the broad behavioral test battery, and integration of proteomics with behavioral outcomes. Limitations include reliance on a single animal model, lack of mechanistic validation for predicted pathways, male-only sampling, and uncertain relevance to humans.

Despite these constraints, the findings suggest that long-term supplementation with aged garlic extract may enhance cognitive resilience and reduce anxiety-like behavior in aging; however, the translational significance for humans remains speculative and requires further mechanistic and clinical studies.