Evidence map›Paper›PMID 40600525›Full record

ArticleCombinatorial chemistry & high throughput screening2026

Apigenin Regulating PI3K/AKT Pathway to Improve Depressive Behavior in Epileptic Rats.

Zhanfang Xie, Yang Zhao, Yanhong Wang, Weijuan Song, Ganggang Li

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Article in Combinatorial chemistry & high throughput screening, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Zhanfang XieDepartment of Pharmacy, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Yang ZhaoDepartment of Pharmacy, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Yanhong WangDepartment of Pharmacy, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Weijuan SongDepartment of Pharmacy, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Ganggang LiDepartment of Pharmacy, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.ORCID 0000-0002-2357-9866

Funding

Key Research and Development Program of Henan Province of China 242102311279Research Project of Henan Science and Technology Think Tank HNKJZK-2025-105BSpecial Project for Traditional Chinese Medicine Research of Henan Province 2025ZY3149Youth Cultivation Plan Project of the Fifth Affiliated Hospital of Zhengzhou University YQ2024016
6 · The paper itself

Abstract

introductionDepression is a common comorbidity in epilepsy, significantly impacting patients' quality of life. The hippocampus, linked to depression and neurodegeneration, is vulnerable in epilepsy. Epileptogenesis involves inflammation, oxidative stress, and neuronal damage, with the PI3K/AKT pathway playing a key role. Apigenin (API), a flavonoid in fruits and vegetables, shows neuroprotective, anti-inflammatory, and anti-apoptotic effects. This study investigates API's mechanisms in a LiCl-pilocarpine epileptic rat model, focusing on hippocampal neurogenesis and PI3K/AKT signaling as potential therapeutic targets.

methodsWe studied the effects of API and valproate (VPA) on depressive behavior and astrocytes in Lithium chloride (LiCl)-pilocarpine-induced epileptic rats. Additionally, we predicted the potential molecular targets of API for treating epilepsy using network pharmacology. Finally, we conducted in vivo experiments to validate the predicted mechanism.

resultsIn the API and VPA groups, there was a reduction in seizure frequency and seizure severity compared with the control group. The model group showed more depressive behavior than the control (CON) group, and these behaviors improved significantly after VPA and API treatment. HE staining showed that both API and VPA treatment improved LiCl-pilocarpine-induced nuclear contraction and cell swelling. Nissl staining demonstrated that Nissl vesicles in the CA3 region of the hippocampus were decreased in the model group, but the neurons were larger, more abundant, and more neatly arranged after API and VPA treatment. In the model group, the p-PI3K/PI3K and p-AKT/AKT protein ratios and PI3K, AKT mRNA expression were reduced, while brain-derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) were markedly increased. API and VPA treatment effectively reversed these changes. DISCUSSION: API reduces seizures and depressive behaviors in LiCl-pilocarpine-induced epileptic rats, comparable to VPA API mitigates hippocampal neuronal damage, preserves Nissl bodies, and suppresses astrocyte activation via the PI3K/AKT pathway, suggesting neuroprotective and anti-inflammatory effects. While API shows promise as an antiepileptic and antidepressant agent, further studies are needed to confirm its direct modulation of PI3K/AKT and efficacy in other epilepsy models.

conclusionOur study suggests that API improves depression in rats and has anti-epilepsy activity, which may be involved in activating the PI3K/AKT pathway to protect astrocytes.

Indexed as

Antidepressive AgentsApigeninDepressionEpilepsyPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktAnimalsDisease Models, AnimalHippocampusLithium ChlorideMalePilocarpineRatsRats, Sprague-DawleySignal TransductionAntidepressive AgentsApigeninLithium ChloridePhosphatidylinositol 3-KinasesPilocarpineProto-Oncogene Proteins c-aktapigeninastrocytedepressive behaviorEpilepsyhippocampalPI3K/AKT

Identifiers

PMID40600525

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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 OpenQuestion graph.