{"title":"Rutin Ameliorates Toxoplasma gondii-Induced Brain Tissue Damage via Inhibiting P2X7R/NLRP3 Pro-Inflammatory and Enhancing PI3K/AKT/Nrf2/HO-1 Antioxidant Signaling Pathway","authors":"Chengquan Han, Biao Wei, Lizeng Guan, Lu Xu","doi":"10.1134/s1062359023606481","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Bain damage caused by <i>Toxoplasma gondii</i> (<i>T. gondii</i>) is associated with increased inflammatory response and oxidative stress. Rutin, a natural product extracted from tobacco leaves and tomatoes, has excellent anti-inflammatory and antioxidant properties in vivo, but its ameliorative effect on <i>T. gondii</i> infection-induced brain tissue damage remain unknown. In this study, mice were acutely infected with RH virulent strains of <i>T. gondii</i>, then treated with 0–50 mg/kg of Rutin. Results showed that Rutin significantly reduced the number of abnormal morphological neurons in the hippocampal region of brain tissue, decreased the concentration of Iba-1, the biomarker of microglia which indicates increased tissue damage and inflammation in the brain; decreased the level of inflammatory factors (TNF-α, IL-6 and IL-1β) in serum and increased the content of antioxidant enzymes (GSH and SOD) in brain tissue; and decreased the enrichment of oxidation products MDA. Results showed significant downregulation of key proteins in the two inflammation-related pathways, TLRs/NF-κB, P2X7R/NLRP3. While the proteins in the antioxidant-related pathways were noticeably upregulated in the <i>T. gondii</i>-infected brain tissue with Rutin treatment. These findings suggest that Rutin ameliorates <i>T. gondii</i>-induced brain tissue damage, may involving in inhibiting the TLRs/NF-κB and P2X7R/NLRP3 inflammatory signaling pathways, and activating the PI3K/AKT/Nrf2/HO-1 antioxidant pathway. The findings could provide some theoretical support for Rutin’s potential therapeutic use in treating <i>T. gondii</i>-related brain damage in the future.</p>","PeriodicalId":55366,"journal":{"name":"Biology Bulletin","volume":"7 1","pages":""},"PeriodicalIF":0.5000,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biology Bulletin","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1134/s1062359023606481","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOLOGY","Score":null,"Total":0}
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Abstract
Bain damage caused by Toxoplasma gondii (T. gondii) is associated with increased inflammatory response and oxidative stress. Rutin, a natural product extracted from tobacco leaves and tomatoes, has excellent anti-inflammatory and antioxidant properties in vivo, but its ameliorative effect on T. gondii infection-induced brain tissue damage remain unknown. In this study, mice were acutely infected with RH virulent strains of T. gondii, then treated with 0–50 mg/kg of Rutin. Results showed that Rutin significantly reduced the number of abnormal morphological neurons in the hippocampal region of brain tissue, decreased the concentration of Iba-1, the biomarker of microglia which indicates increased tissue damage and inflammation in the brain; decreased the level of inflammatory factors (TNF-α, IL-6 and IL-1β) in serum and increased the content of antioxidant enzymes (GSH and SOD) in brain tissue; and decreased the enrichment of oxidation products MDA. Results showed significant downregulation of key proteins in the two inflammation-related pathways, TLRs/NF-κB, P2X7R/NLRP3. While the proteins in the antioxidant-related pathways were noticeably upregulated in the T. gondii-infected brain tissue with Rutin treatment. These findings suggest that Rutin ameliorates T. gondii-induced brain tissue damage, may involving in inhibiting the TLRs/NF-κB and P2X7R/NLRP3 inflammatory signaling pathways, and activating the PI3K/AKT/Nrf2/HO-1 antioxidant pathway. The findings could provide some theoretical support for Rutin’s potential therapeutic use in treating T. gondii-related brain damage in the future.
期刊介绍：
Biology Bulletin (Izvestiya Rossiiskoi Akademii Nauk – Seriya Biologicheskaya) is an interdisciplinary journal of general biology. It focuses on fundamental studies in the fields of cell biology, biochemistry, zoology, botany, physiology, and ecology. This journal publishes current materials of experimental studies and surveys on current problems in general biology. It also publishes information on scientific conferences and new books in the fields of general biology.
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