Prediction of novel traditional Chinese medicine preparations for epilepsy treatment based on GEO database and reverse network pharmacology_Journal of Epilepsy

Authors：

YOU Xiyou , WANG Zhuo , ZHANG Qinqin , LI Yuying , YIN Wenmin ,  ZHAO Luqing ,  YANG Jianzhong

Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University, Taiyuan 030000, China;

Corresponding?author：

ZHAO Luqing, Email: zhaoluqing_shanxi@163.com; YANG Jianzhong, Email: 1595021181@qq.com

Keywords：

Epilepsy; Reverse network pharmacology; GEO database; Traditional Chinese medicine; Multi-target

DOI：

10.7507/2096-0247.202605012

Video：

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Objective To explore the pathogenesis of epilepsy (EP) and predict traditional Chinese medicine (TCM) prescriptions based on the concept of reverse network pharmacology. Methods Differentially expressed genes (DEGs) in EP were screened from the Gene Expression Omnibus (GEO) database. A weighted gene co-expression network analysis (WGCNA) was constructed to identify genes with the highest expression variability, which were then compared with EP target genes obtained from databases including GeneCards, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD). Core targets were screened using the STRING platform. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to elucidate the pathogenesis and signaling pathways of EP. After converting core targets using the UniProt database, active ingredients and corresponding TCM herbs were reversely collected from relevant databases. Cytoscape software was used for visualization and construction of the core target-active ingredient-TCM herb network. Molecular docking verification between core targets and core ingredients was conducted using CB-DOCK2 software, and TCM herbs with high degree values were finally determined. Results A total of 131 EP targets were obtained, and 30 key targets were selected based on degree values. GO enrichment analysis yielded 30 main entries, and KEGG enrichment analysis identified 10 signaling pathways. Seven blood-absorbable ingredients and 20 TCM herbs were matched from the Comparative Toxicogenomics Database (CTD) based on degree values. Molecular docking verification was performed between 6 core target proteins and 7 core ingredients with high degree values, and the results were stable and favorable. A total of 20 TCM herbs were screened out, including Corydalis Rhizoma, Daturae Flos, Bruceae Fructus, and Corydalis Decumbentis Rhizoma. Conclusion The application of reverse network pharmacology thinking and molecular docking technology to predict targets, pathways, ingredients, and TCM prescriptions for epilepsy provides new ideas and theoretical basis for clinical treatment and research.

Citation： YOU Xiyou, WANG Zhuo, ZHANG Qinqin, LI Yuying, YIN Wenmin, ZHAO Luqing, YANG Jianzhong. Prediction of novel traditional Chinese medicine preparations for epilepsy treatment based on GEO database and reverse network pharmacology. Journal of Epilepsy, 2026, 12(4): 281-291. doi: 10.7507/2096-0247.202605012 Copy

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15.	Pu Z, Bao X, Xia S, et al. Serpine1 regulates peripheral neutrophil recruitment and acts as potential target in ischemic stroke. J Inflamm Res, 2022, 15: 2649-2663.
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18.	湯景翔, 王青, 雷鵬. 東莨菪堿的中樞藥理機制研究進展. 南京醫科大學學報(自然科學版), 2023, 43(8): 1161-1171.
19.	吁誠銘, 李金平, 胡先明. 茯苓皮提取物抑制癲癇活性作用. 中成藥, 2017, 39(6): 1288-1290.
20.	Shi Z, Han L, Yang H, et al. From traditional remedy to modern therapy: a comprehensive review of palmatine's multi-target mechanisms and ethnopharmacological potential. Front Pharmacol, 2025, 16: 1624353.
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23.	王文敏, 吳佳輝, 石凌鈺, 等. 鴉膽子中苦木素類成分及其抗炎機制的研究進展. 中國野生植物資源, 2024, 43(9): 88-95.
24.	Jivad N, Heidari-Soureshjani S, Bagheri HS, et al. Anti-seizure effects and mechanisms of berberine: a systematic review. Curr Pharm Biotechnol, 2024, 25(17): 2253-2265.
25.	Meller S, K?ufer C, Gailus B, et al. Scopolamine prevents aberrant mossy fiber sprouting and facilitates remission of epilepsy after brain injury. Neurobiol Dis, 2021, 158: 105446.

1. Bandopadhyay R, Singh T, Ghoneim MM, et al. Recent developments in diagnosis of epilepsy: scope of microRNA and technological advancements. Biology (Basel), 2021, 10(11): 1097.
2. 李志強, 張鴻. 耐藥性癲癇的研究進展. 癲癇雜志, 2022, 8(4): 342-347.
3. 王薇薇, 吳遜. 腦網絡理論在癲癇臨床中的意義及應用. 癲癇雜志, 2024, 10(1): 66-72.
4. Tao F, Cai Y, Deng C, et al. A narrative review on traditional Chinese medicine prescriptions and bioactive components in epilepsy treatment. Ann Transl Med, 2023, 11(2): 129.
5. Tabassum S, Shorter S, Ovsepian SV. Analysis of the action mechanisms and targets of herbal anticonvulsants highlights opportunities for therapeutic engagement with refractory epilepsy. J Mol Med (Berl), 2024, 102(6): 761-771.
6. Lin CH, Hsieh CL. Chinese Herbal Medicine for Treating Epilepsy. Front Neurosci, 2021, 15: 682821.
7. 袁旭, 李政, 王曉天, 等. 中藥及其有效成分在抗癲癇中的作用與機制. 中國中藥雜志, 2019, 44(1): 9-18.
8. Dai P. Protective effects of curcumin on epileptic rodent models by alleviating oxidative stress and inflammation: a meta-analysis and mechanism exploration. Front Pharmacol, 2025, 16: 1602716.
9. 宋雨檬, 趙克明, 楊闖, 等. 基于逆向網絡藥理學及分子對接探討人偏肺病毒感染的發病機制及中藥組方預測. 實用中醫內科雜志, 2026, 40(1): 37-40+159-166.
10. 周文文, 司麗君, 郭君婷, 等. 基于網絡藥理學與體內外模型探討癲癇合劑抗癲癇的作用機制. 中藥藥理與臨床, 2026, 42(2): 25-35.
11. 劉錚楷, 艾進偉, 陳雙舟, 等. 整合加權基因共表達網絡分析與人工神經網絡的骨關節炎-類風濕性關節炎線粒體關鍵基因預測模型構建及靶向中藥預測. 中國藥學雜志, 2026, 61(5): 536-551.
12. Du X, Wang Y, Wang X, et al. Neural circuit mechanisms of epilepsy: maintenance of homeostasis at the cellular, synaptic, and neurotransmitter levels. Neural Regeneration Research, 2026, 21(2): 455–465.
13. 郭鴻儒, 陳燕惠. 炎癥免疫與癲癇. 癲癇雜志, 2021, 7(5): 426-430.
14. Arisi GM, Foresti ML, Katki K, et al. Increased CCL2, CCL3, CCL5, and IL-1β cytokine concentration in piriform cortex, hippocampus, and neocortex after pilocarpine-induced seizures. J Neuroinflammation, 2015, 2(12): 129.
15. Pu Z, Bao X, Xia S, et al. Serpine1 regulates peripheral neutrophil recruitment and acts as potential target in ischemic stroke. J Inflamm Res, 2022, 15: 2649-2663.
16. Qi Y, Cheng H, Wang Y, et al. Revealing the precise role of calretinin neurons in epilepsy: we are on the way. Neurosci Bull, 2022, 38(2): 209-222.
17. Zakharova ET, Sokolov AV, Pavlichenko NN, et al. Erythropoietin and Nrf2: key factors in the neuroprotection provided by apo-lactoferrin. Biometals, 2018, 31(3): 425-443.
18. 湯景翔, 王青, 雷鵬. 東莨菪堿的中樞藥理機制研究進展. 南京醫科大學學報(自然科學版), 2023, 43(8): 1161-1171.
19. 吁誠銘, 李金平, 胡先明. 茯苓皮提取物抑制癲癇活性作用. 中成藥, 2017, 39(6): 1288-1290.
20. Shi Z, Han L, Yang H, et al. From traditional remedy to modern therapy: a comprehensive review of palmatine's multi-target mechanisms and ethnopharmacological potential. Front Pharmacol, 2025, 16: 1624353.
21. Karancsi Z. The impact of quercetin and its methylated derivatives 3-o-methylquercetin and rhamnazin in lipopolysaccharide-induced inflammation in porcine intestinal cells. Antioxidants (Basel, Switzerland), 2022, 11: 1265.
22. Li X, Ji J, Li J, et al. Gut microbiota-bile acid metabolic disorder involved in the cognitive impairments in epilepsy through HO-1 dependent ferroptosis. J Pharm Anal, 2025, 15(11): 101291.
23. 王文敏, 吳佳輝, 石凌鈺, 等. 鴉膽子中苦木素類成分及其抗炎機制的研究進展. 中國野生植物資源, 2024, 43(9): 88-95.
24. Jivad N, Heidari-Soureshjani S, Bagheri HS, et al. Anti-seizure effects and mechanisms of berberine: a systematic review. Curr Pharm Biotechnol, 2024, 25(17): 2253-2265.
25. Meller S, K?ufer C, Gailus B, et al. Scopolamine prevents aberrant mossy fiber sprouting and facilitates remission of epilepsy after brain injury. Neurobiol Dis, 2021, 158: 105446.

Journal of Epilepsy

Prediction of novel traditional Chinese medicine preparations for epilepsy treatment based on GEO database and reverse network pharmacology

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