Broccoli Leaf Phenolics Ameliorate NAFLD via Regulation of EGFR/AKT/SREBP Signaling Pathways and Gut Microbiota

Broccoli leaves are commonly discarded during industrial processing despite being rich in bioactive phytochemicals, resulting in substantial resource waste. This study investigated the protective effects and underlying mechanisms of a microwave-assisted green extract of broccoli leaf phenolics (BLP) against high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD). The LC-MS/MS profiling revealed that BLP is predominantly composed of cinnamic acid derivatives and flavonoids, notably sinapic acid, ferulic acid, kaempferol, and luteolin. In HFD-fed C57BL/6J mice, BLP supplementation significantly ameliorated hepatic steatosis and liver injury, evidenced by reduced serum AST, ALT, and lipid profiles (TG, TC, LDL). Mechanistically, BLP suppressed hepatic lipogenesis via SREBP-1c downregulation, modulated the EGFR/AKT/SREBP signaling pathway, and attenuated inflammatory responses by inhibiting the TLR4/NF-κB pathway and reducing pro-inflammatory cytokines (IL-6, IL-1β, TNF-α). Furthermore, BLP reinforced intestinal barrier integrity by upregulating tight junction proteins () and restored gut microbiota homeostasis, enriching beneficial taxa (, ) while suppressing dysbiosis-associated genera. Overall, BLP could exert hepatoprotective effects via the gut-liver axis, highlighting its immense potential as a value-added, food-derived functional ingredient for NAFLD prevention.