1. Coixol mitigates Toxoplasma gondii infection-induced liver injury by inhibiting the Toxoplasma gondii HSP70/TLR4/NF-κB signaling pathway in hepatic macrophages.
- Author
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Zhou JY, Lu YN, Shen XY, Quan YZ, Lu JM, Jin GN, Liu YM, Zhang SH, Xu GH, Xu X, and Piao LX
- Subjects
- Animals, Female, Mice, Kupffer Cells drug effects, Kupffer Cells metabolism, Liver drug effects, Liver parasitology, Liver metabolism, Liver pathology, Toxoplasmosis drug therapy, Macrophages drug effects, Macrophages metabolism, Macrophages parasitology, Coix chemistry, NF-kappa B metabolism, Toll-Like Receptor 4 metabolism, Mice, Inbred BALB C, Signal Transduction drug effects, HSP70 Heat-Shock Proteins metabolism, Toxoplasma drug effects
- Abstract
Ethnopharmacological Relevance: Coix seed, the dry mature seed kernel of the gramineous plant coix (Coix lacryma-jobi L. var. ma-yuen Stapf), is widely consumed as a traditional Chinese medicine and functional food in China and South Korea. We have previously demonstrated the protective effect of coixol, a polyphenolic compound extracted from coix, against Toxoplasma gondii (T. gondii) infection-induced lung injury. However, the protective effect of coixol on hepatic injury induced by T. gondii infection have not yet been elucidated., Aim of the Study: This study explores the impact of coixol on T. gondii infection-induced liver injury and elucidates the underlying molecular mechanisms., Materials and Methods: Female BALB/c mice and Kupffer cells (KCs) were employed to establish an acute T. gondii infection model in vivo and an inflammation model in vitro. The study examined coixol's influence on the T. gondii-derived heat shock protein 70 (T.g.HSP70)/toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling pathway in T. gondii-infected liver macrophages. Furthermore, a co-culture system of KCs and NCTC-1469 hepatocytes was developed to observe the impact of liver macrophages infected with T. gondii on hepatocyte injury., Results: Coixol notably inhibited the proliferation of tachyzoites and the expression of T.g.HSP70 in mouse liver and KCs, and attenuated pathological liver injury. Moreover, coixol decreased the production of high mobility group box 1, tumor necrosis factor-α, and inducible nitric oxide synthase by suppressing the TLR4/NF-κB signaling pathway in vitro and in vivo. Coixol also mitigated KCs-mediated hepatocyte injury., Conclusions: Coixol protects against liver injury caused by T. gondii infection, potentially by diminishing hepatocyte injury through the suppression of the inflammatory cascade mediated by the T.g.HSP70/TLR4/NF-κB signaling pathway in KCs. These findings offer new perspectives for developing coixol as a lead compound for anti-T. gondii drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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