Lycopus lucidus Turcz. extract ameliorates CCl4-induced liver damage by MAPK/Nrf2 signaling pathways and gut microbiota in mice

This work explored the protection of free phenolic extract from Lycopus lucidus root (FPLR) against liver damage caused by CCl 4 and its underlying mechanisms in mice. Mice were separated into the normal group (control), model group (CCl 4 ), and FPLR group (FPLR+ CCl 4 ). FPLR reduced liver or spleen index, improved liver function, and alleviated histopathological lesions, oxidative stress, and inflammation. Meanwhile, FPLR inhibited protein phosphorylation in the mitogen-activated protein kinases (MAPK) pathway, up-regulated gene and protein expression in the Nuclear Factor erythroid 2-Related Factor 2 (Nrf2) pathway, and down-regulated kelch-like ECH-associated protein 1 (Keap1) expression. Furthermore, FPLR increased the number of beneficial gut microbes, including Bacteroidales_S24_7_group , Lactobacillus, and Parabacteroides distasonis , while lowering the Firmicutes / Bacteroidetes ratio and harmful ones, such as Streptococcaceae , Ruminococcaceae_UCG-014, and Oscillibacter (all p < 0.05). Correlation analysis suggested nine bacteria, including Lactobacillus , Staphylococcus, and Parabacteroides_distasonis , played an important role in preventing liver damage, activating the Nrf2 pathway and inhibiting Keap1. In conclusion, FPLR successfully mitigated CCl 4 -induced liver damage by modulating the MAPK/Nrf2 pathways and gut microbiota. • FPLR improved liver function, alleviated oxidative stress and inflammation. • FPLR inhibited protein phosphorylation in the mitogen-activated protein kinases (MAPK) pathway. • FPLR successfully mitigated CCl 4 -induced liver damage by modulating the gut microbiota.