Systematic evaluation of phenolic compounds and protective capacity of a new mulberry cultivar J33 against palmitic acid-induced lipotoxicity using a simulated digestion method

This research aimed to investigate the protective effects of a new mulberry cultivar J33 with simulated gastrointestinal digestion against palmitic acid (PA)-induced lipotoxicity. LC-MS analysis revealed that the contents of four flavonoid glycosides (quercetin rhamnosylhexoside hexoside, quercetin rhamnosylhexoside, quercetin hexoside, kaempferol rhamnosylhexoside) increased after digestion. Besides, mulberry digest (MBD) at 0.5-2 mg/mL significantly reduced PA-induced lipotoxicity in human hepatocytes, while mulberry extract without digestion (MBE) showed no protection. Further investigations demonstrated that the protection of MBD was attributed to two aspects. On the one hand, MBD could attenuate PA-induced oxidative stress by suppressing ROS accumulation, regulating intracellular glutathione and ameliorating mitochondrial dysfunction. On the other hand, MBD could promote PA incorporation into inert triglycerides (TG) to deal with the acute lipid overload, reducing the lipotoxicity caused by PA. Overall, our research might provide a new perspective of mulberry cultivar J33 in ameliorating non-alcoholic fatty liver disease (NAFLD).