@article{Li2026, 
author = {Ming Li and Jiabin Zong and Yu Zhang and Minghua Zou and Fu Lu and Songqing Pan and Lily Zhang and Liu Yang and Heyang Qin and Zhouhua Li and Haiyan Wen and Wanbin Huang and Zheman Xiao},
title = {Urolithin A pretreatment protects against seizures through IGF-1R Tyr1166/1167 phosphorylation inhibition and enhances the antiseizure effect of valproic acid},
year = {2026},
journal = {Food Science and Human Wellness},
keywords = {urolithin A, epilepsy, combination therapy, IGF-1R},
url = {https://www.sciopen.com/article/10.26599/FSHW.2026.9251341},
doi = {10.26599/FSHW.2026.9251341},
abstract = {Urolithin A (UA), a metabolite derived from gut microbiota that originates from ellagitannins found in pomegranate, berries, and walnuts, has emerged as a promising postbiotic exhibiting mitophagy-inducing and neuroprotective properties. This study examined the antiseizure effects of UA pretreatment and its potential to enhance the efficacy of valproic acid (VPA), a first-line antiseizure medication, using a pilocarpine-induced status epilepticus (SE) rat model. UA significantly reduced seizure stage, prolonged latency, shortened duration, and decreased incidence of seizures, while alleviating SE-induced behavioral and cognitive impairments. Network pharmacology revealed insulin-like growth factor 1 receptor (IGF-1R) as a critical target of UA. Subsequent experiments demonstrated that UA exerts its therapeutic effects by inhibiting the phosphorylation of IGF-1R. Importantly, the combination of UA and VPA yielded enhanced antiseizure effects compared to either treatment alone in mitigating seizures and behavioral comorbidities. These findings suggest that UA may serve as a valuable adjuvant to conventional antiseizure therapy. Additionally, this study elucidates the antiseizure potential of UA as a pomegranate-derived postbiotic, providing experimental evidence from an animal model to support a UA-VPA combination strategy aimed at improving the efficacy of epilepsy treatment.}
}