Synthesis, characterization and MAFLD prevention potential of Ganoderma lucidum spore polysaccharide-stabilized selenium nanoparticles.

The unstability of selenium nanoparticles (SeNPs) results in decreased activity which limits its therapeutic potential. In this study, we utilized Ganoderma lucidum spore polysaccharide (GLP, Mw = 983.96 kDa) as a novel stabilizer to synthesize GLP-SeNPs. GLP-SeNPs (Se/GLP = 1/3) with an average diameter of 149 nm were successfully prepared and it was stable for at least 30 days at 4 °C. It exhibited an orange-red color, zero valence state, amorphous structure, selenium uniform distribution, a zeta potential of -29.73 mV, selenium content of 16.04 %. GLP-SeNPs pretreatment decreased lipid accumulation, reduced ROS content and enhanced SOD and CAT activity in HepG2 cells. Fe and MDA contents were decreased, while GPX4 and GSH activities were increased. All these ameliorated effects could be abolished by NRF2 antagonist ML385. The expression of anti-oxidant genes and iron exporter was up-regulated, while that of pro-oxidant and lipid biosynthesis gene was down-regulated. The GPX4 activity could be reduced by ML385 addition. In conclusion, GLP-SeNPs was successfully constructed at the ratio of 1/3 (Se/GLP). It prevents MAFLD by targeting ferroptosis, including lowering iron overload, inhibiting lipid accumulation and attenuating oxidative stress. The improvement was conducted via activating SLC40A1-mediated iron pathway, ACSL4-mediated lipid metabolism and NRF2-mediated GSH-GPX4 pathway. Therefore, GLP-SeNPs can be used as potential selenium nutritional supplements or adjuvants for MAFLD prevention.