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

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 • FCHM is a green, environmentally friendly biotechnology that promotes healthy largemouth bass growth. • FCHM can activate the Nrf2-Keap1 signaling pathway and alleviate cadmium-induced oxidative stress. • FCHM can alleviate hepatotoxic injury through the gut-liver axis pathway. • The molecular docking technique predicted the targets of action of key components of Chinese herbal medicine.