A composite plant extract attenuates alcohol-induced hepatic lipogenesis via AMPK-FAS signaling and gut-liver axis modulation

Alcoholic liver disease (ALD) is characterized by hepatic lipid dysregulation, oxidative stress, and inflammation, for which effective pharmacological interventions remain limited. In this study, we investigated the hepatoprotective effects of SCF extract, a rationally designed composite plant extract consisting of phospholipidated silymarin (68%), Cynara scolymus extract (21%), and fucoxanthin microcapsule powder (11%), using a Lieber-DeCarli liquid ethanol diet-induced ALD mouse model. SCF extract markedly alleviated alcohol-induced liver injury, normalized hepatic and serum lipid profiles, enhanced antioxidant capacity through glutathione elevation, and suppressed inflammatory responses via cytokine modulation. Transcriptomic analysis combined with RT-qPCR and Western blot assays revealed activation of the AMP-activated protein kinase (AMPK) pathway and suppression of fatty acid synthase (FAS), associated with reduced hepatic de novo lipogenesis. Notably, SCF extract also reshaped gut microbiota composition and short-chain fatty acid production, thereby restoring gut-liver axis homeostasis. Collectively, these findings indicate that SCF extract exerts protective effects against alcohol-induced hepatic injury through multi-target regulation of lipid metabolism, oxidative stress, inflammation, and gut-liver axis homeostasis.