Abstract
Toxoplasma gondii (T. gondii) infection can cause liver injury by inducing inflammation and oxidative stress. The Chinese herbal extract luteoloside (Lut) has considerable anti-inflammatory and antioxidant properties, but its effects on the liver injury during T. gondii infection have not been reported. This study investigated the hepatoprotective effects of Lut by treating T. gondii-infected mice with 0–200 mg/kg doses of Lut and further examined the expression of key proteins in the inflammation and oxidative stress-related pathways in the liver to investigate the potential mechanism of the hepatoprotective effects of Lut. Results showed that Lut remarkably reduced serum ALT and AST levels, considerably decreased inflammatory factors TNF-α, IL-6, and IL-1β, as well as oxidative products MDA, and greatly increased antioxidant enzymes SOD and GSH. The expression of key proteins TLR4, Myd88, TRAF6, p-NF-κB p65 in the TLR4/NF-κB pathway and P2X7R, NLRP3, caspase 1, IL-1β, IL-18 in the P2X7R/NLRP3 pathway were significantly decreased in the liver. And the expression of key proteins Nrf2, HO-1, NQO-1, and GCLC in the Nrf2/HO-1 antioxidant-related pathway was significantly upregulated. In conclusion, Lut attenuated T. gondii-induced liver injury by inhibiting the inflammatory response and enhancing antioxidant capacity. The hepatoprotective mechanisms of Lut are involved in inhibiting TLR4/NF-κB and P2X7R/NLRP3 inflammatory signaling pathways, as well as enhancing the Nrf2/HO-1 antioxidant pathway. These findings not only provide some reference for further exploring the specific hepatoprotective mechanism of Lut during T. gondii infection, but also provide some theoretical basis for the future clinical application of Lut as a hepatoprotective drug in T. gondii infection.
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This study was supported by the National Natural Science Foundation of China (No. 31660614).
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The idea for the paper was conceived by Lu Xu. The experiments were designed by Lu Xu. The experiments were performed by Lu Xu, Chengquan Han, Lizeng Guan. The data were analyzed by Lu Xu and Chengquan Han. First draft of the manuscript was written by Chengquan Han and Lu Xu, and the final version of the manuscript was approved by all the authors.
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Han, C., Guan, L. & Xu, L. Protective effect of luteoloside against Toxoplasma gondii-induced liver injury through inhibiting TLR4/NF-κB and P2X7R/NLRP3 and enhancing Nrf2/HO-1 signaling pathway. Parasitol Res 122, 1333–1342 (2023). https://doi.org/10.1007/s00436-023-07833-3
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DOI: https://doi.org/10.1007/s00436-023-07833-3