Licorice Total Flavonoids and Its Gut-Enriched Lactobacillus plantarum Synergistically Activate the Nrf2 Pathway to Alleviate Liver Injury

Licorice (Glycyrrhiza uralensis Fisch.), a medicinal and food homologous herb, contains licorice total flavonoids (LTF) as key bioactive components with unresolved hepatoprotective mechanisms. In this study, we focused on the mechanism by which LTF improved antioxidant capacity and regulated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway according to network pharmacology. LTF upregulated the expression of Nrf2 and its downstream antioxidant-related factors, thereby enhancing the antioxidant capacity of the RAW264.7 cells. LTF alleviated liver injury in mice by activating the Nrf2 pathway and increased the abundance of Allobaculum, Lactobacillus, and Akkermansia in the gut. We isolated a strain of Lactobacillus plantarum (L. plantarum) from mouse feces. Indeed, both L. plantarum and heat-inactivated L. plantarum alleviated liver injury in mice by activating the Nrf2 pathway. These results suggest that LTF and its upregulated L. plantarum synergistically activate the Nrf2 pathway to alleviate liver injury in mice.