Application of Network Toxicology for Toxicity Assessment of Food: A Case Study on 4-methoxypyridoxine
Abstract
toxicity and epileptic seizures is essential for evaluating the broader effects of medicinal foods. This study employs a network toxicology approach to unravel the complex molecular pathways involved in MPN-induced seizures. Using computational tools and an extensive database,
the study identifies and analyzes potential targets and pathways affected by MPN, offering insights into the health risks associated with white
fruit consumption. Databases such as HERB, ETCM, and GeneCards were used to identify 23 potential targets associated with MPN and epilepsy. The interactions among these targets were analyzed using STRING, followed by Gene Ontology (GO) and KEGG pathway enrichment
analyses to elucidate the biological processes involved, including neuroactive ligand-receptor interactions, the calcium signaling pathway, and
the cGMP-PKG signaling pathway. This study provides valuable insights into the molecular mechanisms by which white fruit consumption
can induce seizures in epileptic patients. The application of network toxicology methods has uncovered these mechanisms and offers a robust
framework for studying other toxicants. Future research should focus on developing targeted interventions to mitigate the health risks associated with poisoning from white fruit consumption.
Keywords
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[1] W. Wang, M. Wang, Y. Ruan, J. Tan, H. Wang, T. Yang, J. Li, Q. Zhou, Ginkgolic Acids Impair Mitochondrial Function by Decreasing
Mitochondrial Biogenesis and Promoting FUNDC1-Dependent Mitophagy, J Agric Food Chem 67 (2019) 10097-10106. 10.1021/acs.
jafc.9b04178.
[2] X. Cui, W. Li, J. Wei, Y. Qi, R. Li, Y. Yang, Y. Shi, X. Meng, Y. Mi, T. Huot, W. Sun, X. Zheng, Assessing the Identity of Commercial
Herbs From a Cambodian Market Using DNA Barcoding, Front Pharmacol 11 (2020) 244. 10.3389/fphar.2020.00244.
[3] Y. Gao, M. Xu, Z. Zheng, Y. Wan, S. Wu, C. Li, Preparation of ZIF-8 and Its Application in Determination of Pyridoxine and Pyridoxal
in Ginkgo Seeds by Ultra-Performance Liquid Chromatography, Foods 11 (2022). 10.3390/foods11142014.
[4] H.S. Jang, S.Y. Roh, E.H. Jeong, B.S. Kim, M.K. Sunwoo, Ginkgotoxin Induced Seizure Caused by Vitamin B6 Deficiency, J Epilepsy
Res 5 (2015) 104-106. 10.14581/jer.15018.
[5] G.H. Lee, S.Y. Sung, W.N. Chang, T.T. Kao, H.C. Du, T.H. Hsiao, M.K. Safo, T.F. Fu, Zebrafish larvae exposed to ginkgotoxin exhibit
seizure-like behavior that is relieved by pyridoxal-5-phosphate, GABA and anti-epileptic drugs, Dis Model Mech 5 (2012) 785-795.
10.1242/dmm.009449.
[6] M. Hong, S. Li, N. Wang, H.Y. Tan, F. Cheung, Y. Feng, A Biomedical Investigation of the Hepatoprotective Effect of Radix salviae
miltiorrhizae and Network Pharmacology-Based Prediction of the Active Compounds and Molecular Targets, Int J Mol Sci 18 (2017).
10.3390/ijms18030620.
[7] X. Yi, F. Wang, Y. Feng, J. Zhu, Y. Wu, Danhong injection attenuates doxorubicin-induced cardiotoxicity in rats via suppression of apoptosis: network pharmacology analysis and experimental validation, Front Pharmacol 13 (2022) 929302. 10.3389/fphar.2022.929302.
[8] M.H. Hernandez, V. Bote, L.A. Serra, M. Cendros, J. Salazar, C. Mestres, S. Guijarro, A. Alvarez, C. Lamborena, I. Mendez, B.
Sanchez, A. Hervas, M.J. Arranz, CES1 and SLC6A2 Genetic Variants As Predictors of Response To Methylphenidate in Autism Spectrum Disorders, Pharmgenomics Pers Med 15 (2022) 951-957. 10.2147/pgpm.S377210.
[9] Z.D. Cen, F. Xie, J.F. Xiao, W. Luo, Rational search for genes in familial cortical myoclonic tremor with epilepsy, clues from recent advances, Seizure 34 (2016) 83-89. 10.1016/j.seizure.2015.12.004.
[10] B. Li, Q. Sun, F. Ding, Q. Xu, N. Kang, Y. Xue, A. Ladron-de-Guevara, H. Hirase, P. Weikop, S. Gong, N. Smith, M. Nedergaard, Antiseizure effects of norepinephrine-induced free fatty acid release, Cell Metab 37 (2025) 223-238.e225. 10.1016/j.cmet.2024.10.011.
[11] S. Li, X. Zhang, Q. Fang, J. Zhou, M. Zhang, H. Wang, Y. Chen, B. Xu, Y. Wu, L. Qian, Y. Xu, Ginkgo biloba extract improved cognitive and neurological functions of acute ischaemic stroke: a randomised controlled trial, Stroke Vasc Neurol 2 (2017) 189-197. 10.1136/
svn-2017-000104.
[12] J. Yang, Y. Sun, J. Chen, Y. Cheng, H. Zhang, T. Gao, F. Xu, S. Pan, Y. Tao, J. Lu, Fermentation of ginkgo biloba kernel juice using
Lactobacillus plantarum Y2 from the ginkgo peel: Fermentation characteristics and evolution of phenolic profiles, antioxidant activities
in vitro, and volatile flavor compounds, Front Nutr 9 (2022) 1025080. 10.3389/fnut.2022.1025080.
[13] I.D. Boateng, A critical review of current technologies used to reduce ginkgotoxin, ginkgotoxin-5-glucoside, ginkgolic acid, allergic
glycoprotein, and cyanide in Ginkgo biloba L. seed, Food Chem 382 (2022) 132408. 10.1016/j.foodchem.2022.132408.
[14] A.S. Granger, Ginkgo biloba precipitating epileptic seizures, Age Ageing 30 (2001) 523-525. 10.1093/ageing/30.6.523.
[15] Z. Shen, S. Pu, X. Cao, M. Tang, S. Wang, D. Bai, G. Jiang, Bioinformatics and network pharmacology analysis of drug targets and
mechanisms related to the comorbidity of epilepsy and migraine, Epilepsy Res 189 (2023) 107066. 10.1016/j.eplepsyres.2022.107066.
[16] O.K. Steinlein, Calcium signaling and epilepsy, Cell Tissue Res 357 (2014) 385-393. 10.1007/s00441-014-1849-1.
[17] S.P. Kelly, M.G. Risley, L.E. Miranda, K. Dawson-Scully, Contribution of a natural polymorphism in protein kinase G modulates electroconvulsive seizure recovery in Drosophila melanogaster, J Exp Biol 221 (2018). 10.1242/jeb.179747.
DOI: http://dx.doi.org/10.70711/frim.v3i2.6018
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