Mechanism of activation of the Nrf2-Keap1 pathway by fermented Chinese herbal medicines via the gut-liver axis to alleviate cadmium-induced hepatotoxicity

作者：Jiang Li, Qiuhong Wu, Yilei Liang, Zhiwen Yang, Guang Wei Fan, Pan Zhou, Xinyue Liu, Yachao Wang · 发表于：Environmental Chemistry and Ecotoxicology · 年份：2025 · DOI：10.1016/j.enceco.2025.06.014 · 被引用次数：5 · 研究领域：Heavy Metal Exposure and Toxicity、Trace Elements in Health、Heavy Metals in Plants

Fermented Chinese herbal medicines (FCHM) as green feed additives are environmentally friendly, residue-free, and non-tolerant. The intention of this study was to investigate the mitigating effect of FCHM on cadmium-induced toxicity injury in largemouth bass. The experiment was set up with eight groups of CD (0, 1.024, 1.537, and 2.306 mg/L) and CD + FCHM (0, 1.024, 1.537, and 2.306 mg/L). During the cadmium exposure period, the CD group was fed a basal diet and the CD + FCHM group was fed a basal diet supplemented with 1 % FCHM for 60 days. The results showed that 1 % FCHM decreased the levels of ROS and MDA content, increased the expression of CAT, SOD, and GSH-PX, and alleviated histopathological damage. Additionally, 1 % FCHM activated the Nrf2-Keap1 pathway and decreased oxidative stress, inflammatory response, and apoptosis, while 1 % FCHM upregulated intestinal barrier genes to repair intestinal damage, and 1 % FCHM improved the intestinal flora structure, increased the abundance of Firmicutes , and decreased the abundance of Proteobacteria . Molecular docking showed that GLU, HIS, and ASP residues were important sites for cadmium to exert toxic effects. Meanwhile, multiple active FCHM components alleviated cadmium-induced hepatotoxicity injury by activating the hepatic Nrf2-Krap1 pathway via the gut-liver axis pathway. This study provides new scientific insights and a theoretical basis for the mechanism of FCHM to alleviate the toxicity of heavy metal cadmium