Evidence map›Paper›PMID 42338596›Full record

ArticleFrontiers in immunology2026

TPPU protects against seizures and seizure-associated comorbidities by inhibiting the Akt/mTOR signaling pathway in KA-induced convulsant mice.

Rong Tang, Banglian Hu, Sulan Xie, Yijun Shen, Ziwei Wang, Xingyi Wang, Xiaohua Huang, Guoqiang Fei, Weifeng Peng, Honghua Zheng and 2 more

Abstract read
In one paragraph

Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Rong Tang *Department of Neurology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China.
Banglian Hu *Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, China.
Sulan XieFujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, China.
Yijun ShenDepartment of Neurology, Shanghai Geriatric Medical Center, Shanghai, China.
Ziwei WangFujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, China.
Xingyi WangFujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, China.
Xiaohua HuangBasic Medical Sciences, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Guoqiang FeiDepartment of Neurology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China.
Weifeng PengDepartment of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China.
Honghua ZhengFujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, China.
Jing DingDepartment of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China.
Xin WangDepartment of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Shared pathophysiological mechanisms exist between epilepsy and its associated comorbidities, with neuroinflammation playing a key role. 1-Trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) is a soluble epoxide hydrolase (sEH) inhibitor that exhibits potent, broad-spectrum anti-inflammatory effects by preventing the hydrolysis of epoxyeicosatrienoic acids (EETs). However, the potential anti-epileptic and comorbidity-alleviating effects of TPPU, along with the underlying molecular mechanisms, remain to be elucidated. Methods: Electroencephalogram (EEG) recordings and Racine score were used to monitor seizures. Behavioral tests were employed to assess seizure-associated cognitive and anxiety-like comorbidities in mice. Whole-cell patch-clamp recordings were used to evaluate synaptic function. RNA-sequencing was conducted to elucidate the molecular mechanisms underlying the neuroprotective effects of TPPU in the KA-induced chronic epileptic model. Results: Behavioral assessments, EEG monitoring, and whole-cell patch-clamp recordings revealed that TPPU significantly mitigated seizure severity and anxiety/depressive-like behaviors, and enhanced cognitive function in kainic acid (KA)-induced chronic epileptic mice. TPPU exhibited neuroprotective properties by reducing neuronal apoptosis and neuroinflammation. Bulk RNA-sequencing analysis indicated that TPPU protected against neuroinflammation during epileptogenesis. Mechanistic investigations revealed that TPPU suppresses Akt/mTOR pathway activation. Conclusions: Our findings establish the Akt/mTOR axis as a critical pathway mediating the protective actions of TPPU against epilepsy and its comorbidities in murine models. This work not only advances our understanding of epilepsy pathophysiology but also identifies novel targets for the development of comprehensive therapeutic strategies.

Indexed as

Neuroprotective AgentsProto-Oncogene Proteins c-aktSeizuresTOR Serine-Threonine KinasesAnimalsAnticonvulsantsComorbidityDisease Models, AnimalEpoxide HydrolasesKainic AcidMaleMiceMice, Inbred C57BLPhenylurea CompoundsPiperidinesSignal Transduction1-trifluoromethoxyphenyl-3-(1-propionylpiperidine-4-yl)ureaAnticonvulsantsEpoxide HydrolasesKainic AcidmTOR protein, mouseNeuroprotective AgentsPhenylurea CompoundsPiperidinesProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesAkt/mTOR axisastrocytescomorbiditiesepilepsyneuroinflammationTPPU

Identifiers

PMID42338596
PMCPMC13283869

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.