Malvidin-3-O-Glucoside from Blueberry Ameliorates Nonalcoholic Fatty Liver Disease by Regulating Transcription Factor EB-Mediated Lysosomal Function and Activating the Nrf2/ARE Signaling Pathway

Nonalcoholic fatty liver disease (NAFLD) has become a universal health issue, whereas there is still a lack of widely accepted therapy until now. Clinical research studies have shown that blueberry could effectively regulate the lipid metabolism, thereby improving obesity-related metabolic syndromes; however, the specific active substances and mechanisms remain unclear. Herein, the effects of the major 10 kinds of anthocyanins from blueberry against NAFLD were investigated using an free fatty acid (FFA)-induced cell model. Among these anthocyanins, malvidin-3-O-glucoside (M3G) and malvidin-3-O-galactoside (M3Ga) could remarkably ameliorate FFA-induced lipid accumulation. Besides, M3G and M3Ga also inhibited oxidative stress via suppressing reactive oxygen species and superoxide anion overproduction, increasing glutathione levels, and enhancing activities of antioxidant enzymes. Further studies unveiled that the representative anthocyanin M3G-upregulated transcription factor EB (TFEB)-mediated lysosomal function possibly interacted with TFEB and activated the Nrf2/ARE (antioxidant responsive element) signaling pathway. Overall, this study enriched the knowledge about the health-promoting effects of blueberry anthocyanins against NAFLD and provided ideas for the development of functional foods of blueberry anthocyanins.