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Article Dans Chinois | WPRIM | ID: wpr-981327

Résumé

This study aimed to demonstrate the effect of Banxia Baizhu Tianma Decoction(BBTD) on realizing withdrawal of anti-epileptic drugs and explore the relationship between BBTD and the amino acid metabolism by transcriptomic analysis in the rat model of epilepsy induced by lithium chloride-pilocarpine. The rats with epilepsy were divided into a control group(Ctrl), an epilepsy group(Ep), a BBTD & antiepileptic drug integrative group(BADIG), and an antiepileptic drug withdrawal group(ADWG). The Ctrl and Ep were given ultrapure water by gavage for 12 weeks. The BADIG was given BBTD extract and carbamazepine solution by gavage for 12 weeks. The ADWG was given carbamazepine solution and BBTD extract by gavage for the former 6 weeks, and then only given BBTD extract for the latter 6 weeks. The therapeutic effect was evaluated by behavioral observation, electroencephalogram(EEG), and hippocampal neuronal morphological changes. High-throughput sequencing was used to obtain amino acid metabolism-related differen-tial genes in the hippocampus, and the mRNA expression in the hippocampus of each group was verified by real-time quantitative polymerase chain reaction(RT-qPCR). The hub genes were screened out through protein-protein interaction(PPI) network, and Gene Ontology(GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed. Two ceRNA networks, namely circRNA-miRNA-mRNA and lncRNA-miRNA-mRNA, were constructed for ADWG vs BADIG. The experimental results showed that compared with those in Ep, rats in ADWG were significantly improved in the behavioral observation, EEG, and hippocampal neuronal impairment. Thirty-four amino acid metabolism-related differential genes were obtained by transcriptomic analysis, and the sequencing results were confirmed by RT-qPCR. Eight hub genes were obtained through PPI network, involving several biological processes, molecular functions, and signal pathways related to amino acid metabolism. Finally, the circRNA-miRNA-mRNA ternary transcription network of 17 circRNA, 5 miRNA, and 2 mRNA, and a lncRNA-miRNA-mRNA ternary network of 10 lncRNA, 5 miRNA, and 2 mRNA were constructed in ADWG vs BADIG. In conclusion, BBTD can effectively achieve the withdrawal of antiepileptic drugs, which may be related to the transcriptomic regulation of amino acid metabolism.


Sujets)
Rats , Animaux , ARN circulaire/génétique , Transcriptome , ARN long non codant/génétique , Anticonvulsivants , microARN/génétique , ARN messager , Carbamazépine , Acides aminés , Réseaux de régulation génique
2.
Article Dans Anglais | WPRIM | ID: wpr-258841

Résumé

We evaluated the antimutagenic effects of 10 kinds of bioactive phytochemicals and some phytochemical combinations against methotrexate (MTX)-induced genotoxicity by the umu test in Salmonella typhimurium TA1535/pSK1002 combined with a micronucleus assay. We observed that allicin, proanthocyanidins, polyphenols, eleutherosides, and isoflavones had higher antimutagenic activities than the other five types of bioactive phytochemicals. At the highest dose tested, MTX-induced genotoxicity was inhibited by 25%-75%. Kunming mice treated by MTX along with bioactive phytochemical combinations showed significant reduction in micronucleus induction and sperm abnormality rate (P<0.01). These results indicate that bioactive phytochemical combinations can be potentially used as new cytoprotectors.


Sujets)
Animaux , Femelle , Mâle , Souris , Antimétabolites antinéoplasiques , Cytoprotection , Évaluation préclinique de médicament , Méthotrexate , Tests de micronucleus , Phytothérapie , Extraits de plantes , Répartition aléatoire , Salmonella typhimurium
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