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Vitamin D Relieves Epilepsy Symptoms and Neuroinflammation in Juvenile Mice by Activating the mTOR Signaling Pathway via RAF1: Insights from Network Pharmacology and Molecular Docking Studies

文献类型：期刊论文

作者Lu, Tiantian6,7; Chen, Xiuling5; Zhang, Qin4; Shang, Kun3; Yang, Xiaogui6; Xiang, Wei1,2,7
刊名NEUROCHEMICAL RESEARCH
出版日期2024-06-05
页码14
关键词Epilepsy Neuroinflammation Vitamin D RAF1 mTOR signaling pathway Network pharmacology Molecular docking
ISSN号0364-3190
DOI10.1007/s11064-024-04176-y
英文摘要Epilepsy is a common neurological disorder, and the exploration of potential therapeutic drugs for its treatment is still ongoing. Vitamin D has emerged as a promising treatment due to its potential neuroprotective effects and anti-epileptic properties. This study aimed to investigate the effects of vitamin D on epilepsy and neuroinflammation in juvenile mice using network pharmacology and molecular docking, with a focus on the mammalian target of rapamycin (mTOR) signaling pathway. Experimental mouse models of epilepsy were established through intraperitoneal injection of pilocarpine, and in vitro injury models of hippocampal neurons were induced by glutamate (Glu) stimulation. The anti-epileptic effects of vitamin D were evaluated both in vivo and in vitro. Network pharmacology and molecular docking analysis were used to identify potential targets and regulatory pathways of vitamin D in epilepsy. The involvement of the mTOR signaling pathway in the regulation of mouse epilepsy by vitamin D was validated using rapamycin (RAPA). The levels of inflammatory cytokines (TNF-alpha, IL-1 beta, and IL-6) were assessed by enzyme-linked immunosorbent assay (ELISA). Gene and protein expressions were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) staining was used to analyze the apoptosis of hippocampal neurons. In in vivo experiments, vitamin D reduced the Racine scores of epileptic mice, prolonged the latency of epilepsy, and inhibited the production of TNF-alpha, IL-1 beta, and IL-6 in the hippocampus. Furthermore, network pharmacology analysis identified RAF1 as a potential target of vitamin D in epilepsy, which was further confirmed by molecular docking analysis. Additionally, the mTOR signaling pathway was found to be involved in the regulation of mouse epilepsy by vitamin D. In in vitro experiments, Glu stimulation upregulated the expressions of RAF1 and LC3II/LC3I, inhibited mTOR phosphorylation, and induced neuronal apoptosis. Mechanistically, vitamin D activated the mTOR signaling pathway and alleviated mouse epilepsy via RAF1, while the use of the pathway inhibitor RAPA reversed this effect. Vitamin D alleviated epilepsy symptoms and neuroinflammation in juvenile mice by activating the mTOR signaling pathway via RAF1. These findings provided new insights into the molecular mechanisms underlying the anti-epileptic effects of vitamin D and further supported its use as an adjunctive therapy for existing anti-epileptic drugs.
WOS关键词RAF/MEK/ERK PATHWAY ; DRUG-RESISTANCE ; HIPPOCAMPUS ; SENSITIVITY ; PROGRESSION ; APOPTOSIS ; CHILDREN ; SEIZURE ; SYSTEM ; CORTEX
资助项目Hainan Provincial Health Industry Research Project
WOS研究方向Biochemistry & Molecular Biology ; Neurosciences & Neurology
语种英语
WOS记录号WOS:001242325200004
出版者SPRINGER/PLENUM PUBLISHERS
资助机构Hainan Provincial Health Industry Research Project
源URL[http://ir.idsse.ac.cn/handle/183446/11566]  
专题深海科学研究部_深海生物学研究室_深海微生物活性物质研究组
通讯作者Xiang, Wei
作者单位1.Hainan Med Univ, Natl Hlth Commiss NHC Key Lab Trop Dis Control, Haikou 570216, Peoples R China
2.Hainan Med Univ, Hainan Women & Childrens Med Ctr, Haikou 570312, Peoples R China
3.Chinese Acad Sci, Inst Deep sea Sci & Engn, Sanya 572000, Peoples R China
4.Hainan Women & Childrens Med Ctr, Dept Neurosurg, Haikou 570312, Peoples R China
5.Cent South Univ, Dept Pediat Med, Xiangya Sch Med, Affiliated Haikou Hosp, Haikou 570208, Peoples R China
6.Haikou Maternal & Child Hlth Hosp, Dept Neonatol, Haikou 570203, Peoples R China
7.Hainan Med Univ, Sch Pediat, Haikou 571199, Peoples R China
推荐引用方式
GB/T 7714		 Lu, Tiantian,Chen, Xiuling,Zhang, Qin,et al. Vitamin D Relieves Epilepsy Symptoms and Neuroinflammation in Juvenile Mice by Activating the mTOR Signaling Pathway via RAF1: Insights from Network Pharmacology and Molecular Docking Studies[J]. NEUROCHEMICAL RESEARCH,2024:14.
APA Lu, Tiantian,Chen, Xiuling,Zhang, Qin,Shang, Kun,Yang, Xiaogui,&Xiang, Wei.(2024).Vitamin D Relieves Epilepsy Symptoms and Neuroinflammation in Juvenile Mice by Activating the mTOR Signaling Pathway via RAF1: Insights from Network Pharmacology and Molecular Docking Studies.NEUROCHEMICAL RESEARCH,14.
MLA Lu, Tiantian,et al."Vitamin D Relieves Epilepsy Symptoms and Neuroinflammation in Juvenile Mice by Activating the mTOR Signaling Pathway via RAF1: Insights from Network Pharmacology and Molecular Docking Studies".NEUROCHEMICAL RESEARCH (2024):14.

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来源：深海科学与工程研究所

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