薏苡仁是禾本科植物薏苡仁（Coix lacryma-jobi L. var. ma-yuen Stapf）的干燥成熟种子仁，在中国和韩国作为中药和功能食品广泛消费。我们之前已经证明了薏苡仁醇（一种从薏苡仁中提取的多酚化合物）对弓形虫（T. gondii）感染引起的肺损伤的保护作用。然而薏苡仁醇对弓形虫感染所致肝损伤的保护作用尚未阐明。本研究探讨薏苡仁醇对弓形虫感染所致肝损伤的影响并阐明其潜在分子机制。雌性BALB/c小鼠采用Kupffer细胞（KCs）建立体内急性弓形虫感染模型和体外炎症模型。该研究检测了薏苡仁醇对弓形虫感染的肝脏巨噬细胞中弓形虫衍生的热休克蛋白 70 (T.g.HSP70)/Toll 样受体 4 (TLR4)/核因子 (NF)-κB 信号通路的影响。此外，还建立了KCs和NCTC-1469肝细胞的共培养体系，观察弓形虫感染的肝巨噬细胞对肝细胞损伤的影响。薏苡素显着抑制小鼠肝脏和KCs中速殖子的增殖和T.g.HSP70的表达，并减轻病理性肝损伤。此外，薏苡仁醇通过抑制体外和体内的TLR4/NF-κB信号通路，减少高迁移率族蛋白1、肿瘤坏死因子-α和诱导型一氧化氮合酶的产生。薏苡仁醇还可以减轻 KCs 介导的肝细胞损伤。薏苡仁醇可以通过抑制 KCs 中 T.g.HSP70/TLR4/NF-κB 信号通路介导的炎症级联反应来减少肝细胞损伤，从而防止弓形虫感染引起的肝损伤。这些发现为开发薏苡仁醇作为抗 T 细胞的先导化合物提供了新的视角。弓形虫药物。版权所有 © 2024。由 Elsevier B.V. 出版。

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.This study explores the impact of coixol on T. gondii infection-induced liver injury and elucidates the underlying molecular mechanisms.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.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.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.Copyright © 2024. Published by Elsevier B.V.