Diffusion MRI Biomarkers of White Matter Damage in Traumatic Brain Injury

Ly, Maria; Ji, Samuel S.; Yassa, Michael A.

doi:10.1007/978-1-4614-9123-1_5

Cited by 1 publication

(1 citation statement)

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“…Densefruit pittany root-bark has antibacterial, anti-in ammatory, antiallergic, and immunomodulatory properties and can be used to treat dermatoses such as tinea pedis, skin itching, and psoriasis [8,9]. Furthermore, a toxicological study of densefruit pittany root-bark [10][11][12]indicates that long-term administration may cause organ toxicity. However, its precise toxic components and toxic mechanism remain unknown.…”

Section: Introductionmentioning

confidence: 99%

A Study to Explore the Substance Basis and Mechanism of Action of the Potential Intestinal-Hepatic-Brain Toxicity of Densefruit Pittany Root-Bark Based on Toxicological Evidence Chain (TEC)

Xu,

Sun,

Wang

et al. 2023

Preprint

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Background Densefruit pittany root-bark is derived from the dried root bark of rutaceae Baixian, a traditional Chinese medicine widely used to treat eczema, psoriasis, and other skin diseases in China. However, in recent years, there have been an increasing number of reports about its negative effects. The potential toxic components and targets of densefruit pittany root-bark intestinal-liver-brain toxicity were screened in this study using pharmacochemistry and network drug/toxicology, molecular docking and molecular dynamics simulation, and were verified by evidence of adverse outcome (AOE).Methods HPLC was used to characterise the densefruit pittany root-bark.TCMSP, TCM-ID, TCM@Taiwan, and CTD databases are used to filter Densefruit pittany root-bark. PharmMapper, SwissTargetPrediction, GeneCards, DisGeNET, and OMIM databases were used to predict the targets of Dense Fruit Root-Bark-induced intestinal-liver-brain tissue damage, and the intersecting targets were chosen for PPI protein interaction analysis, KEGG pathway analysis, and GO enrichment analysis. To depict the core regulatory network, a "drug-compound-toxic target-pathway" map was created using Cytoscape software. The binding affinity and reliability were investigated using molecular docking and molecular dynamics simulation. Finally, HPLC, HE staining, immunohistochemistry, and WB were used to confirm AOE.Results Three compounds in densefruit pittany root-bark were tested, and 125 targets were found to be related to the intestinal-liver-brain toxicity caused by Dense fruit pittance root-bark. The primary targets, according to PPI network analysis, were AKT1, JUN, RELA, SRC, and TP53.Furthermore, GO/KEGG enrichment analysis revealed that densefruit pittany root-bark may modulate Lipid and atherosclerosis, fluid shear stress and atherosclerosis, and the TNF signalling pathway to cause intestinal-liver-brain tissue injury. According to the "herb-compound-toxic target-pathway-organ damage" network, dictamine, obakunone, and fraxinone may be therapeutic or main toxic compounds. Molecular docking and molecular dynamics simulation results show that the core compound has a high affinity for the target.Conclusion This study clarified the mechanism of densefruit pittany root-bark-induced intestinal-liver-brain toxicity, which was the first study on the toxicity of densefruit pittany root-bark based on the concept of TEC, and provided a reference for future research on the toxicity mechanism of densefruit pittany root-bark. However, further experimental validation is required before using densefruit pittany root-bark in clinical practise.

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Section: Introductionmentioning

confidence: 99%