Non-alcoholic fatty liver disease (NAFLD) is a global epidemic, tightly linked to the rising incidence of obesity and excessive body weight. This study sought to investigate the hepatoprotective potential of Melosira nummuloides using in vitro and in vivo NAFLD models. In vitro experiments with palmitate (PA)-treated HepG2 cells demonstrated the remarkable efficacy of M. Nummuloides ethanol extract ME, enhancing P-AMPK and HO-1 while suppressing NF-κB and ERK phosphorylation, surpassing other extracts. ME increased the mRNA expression of genes related to fatty acid oxidation and decreased lipogenesis while simultaneously downregulating the mRNA expression of inflammatory cytokines and upregulating antioxidant enzyme mRNA levels. In a high-fat diet (HFD)-fed NAFLD mice, ME treatment resulted in lower average body weight, body weight gain, and liver weight. Serum analysis confirmed reduced TG and T-CHO, increased HDL levels, and attenuated liver injury markers (AST and ALT) resulting in a notable decrease in hepatic lipid deposition which is validated through histological examination. Furthermore, western blot analysis revealed ME boosted proteins related to lipid oxidation and antioxidants such as P-AMPK, PPARα, and HO-1 while diminishing inflammation and lipogenesis-associated protein such as P-NFκB, P-ERK, and SREBP-1 in the livers. ME also curtailed lipogenesis and bolstered lipid oxidation as observed in HepG2 cells. In conclusion, ME exhibits potent hepatoprotective effects, highlighting its potential as a therapeutic agent for NAFLD. This research was supported by Korea Institute of Marine Science & Technology Promotion (KIMST) funded by the Ministry of Oceans and Fisheries, Korea (20220255) and by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education(2016R1A6A1A03012862).
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