Objective:

To systematically synthesize preclinical evidence on the effects of thymol (and thymol-rich preparations) on cognition and Alzheimer’s disease–related pathophysiology in animal and neuronal cell models, and to evaluate underlying mechanisms by which thymol exerts these effects. 

Background:

Alzheimer’s disease (AD) involves progressive cognitive decline driven by amyloid-β accumulation causing oxidative stress, synaptic dysfunction, and neuroinflammation. Thymol, a bioactive monoterpenoid phenol derived from thyme species, has demonstrated neuroprotective properties in experimental studies. However, evidence on its efficacy across preclinical AD models has not been systematically synthesized. 

Design/Methods:

We conducted a systematic search of PubMed, Scopus, and Web of Science in accordance with PRISMA guidlines for controlled in vivo and in vitro studies evaluating thymol in Alzheimer’s-relevant models. Reviewers independently screened abstracts and full texts using predefined inclusion and exclusion criteria; after screening, nine studies met eligibility. Data were extracted into a pre-specified table recording study design, sample size, intervention details, outcomes, and key results. Risk of bias was evaluated using SYRCLE criteria, with independent scoring and consensus-based resolution of disagreements.

Results:

Out of the nine included studies, two were in vivo and seven were in vitro. Animal experiments administered thymol at 0.5–80 mg/kg and assessed cognition using the Morris water maze, Passive avoidance, Radial arm maze, and Novel object recognition tests; thymol consistently improved spatial learning, memory retention, and behavioral performance. Mechanistic data indicated reduced oxidative stress and Aβ-induced neurotoxicity, preservation of synaptic plasticity, increased acetylcholine availability, and modulation of PKC and MAPK/Nrf2 signaling. In vitro studies corroborated these effects, showing increased cell viability, decreased ROS production, and restored cholinergic function.

Conclusions:

Thymol demonstrates consistent neuroprotective and cognition-enhancing effects across preclinical AD models, acting through multiple mechanisms relevant to AD pathogenesis. These findings support thymol as a promising therapeutic candidate; however, clinical trials are required to determine its applicability in humans.