Luteolin for Alzheimer's disease and related cognitive impairment: a systematic review and meta-analysis of efficacy and molecular mechanisms.
- 1College of Integrated Traditional Chinese and Western Medicine, Changchun University of Chinese Medicine, Changchun, Jilin Province, China.
- 2Department of Cardiology, The Third Affiliated Clinical Hospital of Changchun University of Chinese Medicine, Changchun, Jilin Province, China.
- 3Department of Neurology, The Third Affiliated Clinical Hospital of Changchun University of Chinese Medicine, Changchun, Jilin Province, China.
Abstract
The multifactorial pathogenesis of Alzheimer's disease (AD) renders conventional single-target therapies largely ineffective. Luteolin, a natural flavonoid, has demonstrated promising pleiotropic neuroprotective potential. This study aims to systematically evaluate the preclinical efficacy and multi-target mechanisms of luteolin in rodent models of AD and associated cognitive impairment. Eight major electronic databases were systematically searched from January 1, 2000 to June 1, 2026. In vivo preclinical studies evaluating luteolin monotherapy in AD-specific and general cognitive impairment rodent models were included. Methodological quality was assessed using the SYRCLE risk of bias tool. Standardized mean differences and 95% confidence intervals were calculated using a random-effects model. Fifteen eligible studies were included. Meta-analysis revealed that luteolin significantly ameliorated cognitive and memory impairments in both AD-specific and non-AD cognitive impairment models. Mechanistically, luteolin significantly restored redox homeostasis and suppressed neuroinflammatory cascades at both transcriptional and translational levels. Subgroup analyses indicated that oral administration and prolonged interventions were associated with significant efficacy; however, these observations are heavily influenced by study-level confounding and cannot conclusively establish pharmacokinetic superiority. Furthermore, the certainty of evidence is limited by predominantly unclear risks of bias, substantial statistical heterogeneity, and potential publication bias. Current preclinical evidence suggests that luteolin is a promising multi-target neuroprotective candidate for AD and related cognitive impairments, highlighted by its anti-inflammatory and antioxidant properties. However, given the substantial methodological limitations and extremely large pooled effect sizes, these findings must be interpreted with caution. Future research must prioritize rigorous preclinical designs, advanced brain-targeted delivery systems, and GLP-compliant toxicological profiling before clinical translation.
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BibTeX
@article{xin2026luteolin,
title = {{Luteolin for Alzheimer's disease and related cognitive impairment: a systematic review and meta-analysis of efficacy and molecular mechanisms.}},
author = {Jixuan Xin and Xilai Teng and Hongyan Su and Xiancheng Wang and Mingquan Li},
journal = {Frontiers in medicine},
year = {2026},
month = oct,
doi = {10.3389/fmed.2026.1976119},
url = {https://europepmc.org/article/MED/42953065},
note = {CC BY},
}
RIS
TY - JOUR
TI - Luteolin for Alzheimer's disease and related cognitive impairment: a systematic review and meta-analysis of efficacy and molecular mechanisms.
AU - Jixuan Xin
AU - Xilai Teng
AU - Hongyan Su
AU - Xiancheng Wang
AU - Mingquan Li
PY - 2026
DA - 2026/10/14
JO - Frontiers in medicine
DO - 10.3389/fmed.2026.1976119
UR - https://europepmc.org/article/MED/42953065
AB - The multifactorial pathogenesis of Alzheimer's disease (AD) renders conventional single-target therapies largely ineffective. Luteolin, a natural flavonoid, has demonstrated promising pleiotropic neuroprotective potential. This study aims to systematically evaluate the preclinical efficacy and multi-target mechanisms of luteolin in rodent models of AD and associated cognitive impairment. Eight major electronic databases were systematically searched from January 1, 2000 to June 1, 2026. In vivo preclinical studies evaluating luteolin monotherapy in AD-specific and general cognitive impairment rodent models were included. Methodological quality was assessed using the SYRCLE risk of bias tool. Standardized mean differences and 95% confidence intervals were calculated using a random-effects model. Fifteen eligible studies were included. Meta-analysis revealed that luteolin significantly ameliorated cognitive and memory impairments in both AD-specific and non-AD cognitive impairment models. Mechanistically, luteolin significantly restored redox homeostasis and suppressed neuroinflammatory cascades at both transcriptional and translational levels. Subgroup analyses indicated that oral administration and prolonged interventions were associated with significant efficacy; however, these observations are heavily influenced by study-level confounding and cannot conclusively establish pharmacokinetic superiority. Furthermore, the certainty of evidence is limited by predominantly unclear risks of bias, substantial statistical heterogeneity, and potential publication bias. Current preclinical evidence suggests that luteolin is a promising multi-target neuroprotective candidate for AD and related cognitive impairments, highlighted by its anti-inflammatory and antioxidant properties. However, given the substantial methodological limitations and extremely large pooled effect sizes, these findings must be interpreted with caution. Future research must prioritize rigorous preclinical designs, advanced brain-targeted delivery systems, and GLP-compliant toxicological profiling before clinical translation.
SN - 2296-858X
ER -