Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, China.
Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, China.
J Ethnopharmacol. 2024 Dec 5;335:118694. doi: 10.1016/j.jep.2024.118694. Epub 2024 Aug 13.
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.
薏苡仁，禾本科植物薏苡（Coix lacryma-jobi L. var. ma-yuen Stapf）的干燥成熟种子仁，在中国和韩国被广泛用作传统中药和功能性食品。我们之前已经证明了从薏苡仁中提取的多酚化合物薏苡仁醇对刚地弓形虫（Toxoplasma gondii，T. gondii）感染引起的肺损伤的保护作用。然而，薏苡仁醇对刚地弓形虫感染引起的肝损伤的保护作用尚未阐明。
本研究旨在探讨薏苡仁醇对刚地弓形虫感染诱导的肝损伤的影响，并阐明其潜在的分子机制。
采用雌性 BALB/c 小鼠和枯否细胞（KCs）建立体内刚地弓形虫感染模型和体外炎症模型。研究检测了薏苡仁醇对刚地弓形虫热休克蛋白 70（T.g.HSP70）/Toll 样受体 4（TLR4）/核因子（NF）-κB 信号通路的影响在感染刚地弓形虫的肝巨噬细胞中。此外，建立了枯否细胞和 NCTC-1469 肝细胞的共培养系统，以观察感染刚地弓形虫的肝巨噬细胞对肝细胞损伤的影响。
薏苡仁醇显著抑制了速殖子的增殖和小鼠肝和 KCs 中 T.g.HSP70 的表达，并减轻了病理性肝损伤。此外，薏苡仁醇通过抑制 TLR4/NF-κB 信号通路，降低了高迁移率族蛋白 1、肿瘤坏死因子-α和诱导型一氧化氮合酶的产生，无论是在体外还是体内。薏苡仁醇还减轻了 KCs 介导的肝细胞损伤。
薏苡仁醇可预防刚地弓形虫感染引起的肝损伤，可能是通过抑制 KCs 中 T.g.HSP70/TLR4/NF-κB 信号通路介导的炎症级联反应，减轻肝细胞损伤。这些发现为开发薏苡仁醇作为抗刚地弓形虫药物的先导化合物提供了新的视角。
