Rutin Ameliorates Toxoplasma gondii-Induced Brain Tissue Damage via Inhibiting P2X7R/NLRP3 Pro-Inflammatory and Enhancing PI3K/AKT/Nrf2/HO-1 Antioxidant Signaling Pathway

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.