Protective effect of mulberry fruit anthocyanin on human hepatocyte cells (LO2) and Caenorhabditis elegans under hyperglycemic conditions

•MAE reduced glucose-induced oxidative stress in LO2 cells.•MAE recovered shortened lifespan of C. elegans under a hyperglycemic condition.•MAE could not restore shortened longevity in daf-2 mutant fed with a glucose diet.•MAE intervention led to alteration of 92 genes expression by RNA-Seq analysis.

Type 2 diabetes is a chronic disease and hyperglycemia is important in the pathogenesis of diabetic complications. Exposure of LO2 cells to high glucose resulted in cellular glucose consumption and uptake decreases, reactive oxygen species (ROS) and superoxide anion (O2−) accumulation and mitochondrial dysfunction, which could be partly recovered by mulberry anthocyanin extract (MAE). And these protective effects were partly associated with regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream targets. As the insulin-signaling pathway is evolutionarily well conserved from Caenorhabditis elegans to mammals, C. elegans has been considered as a model system to study effects of glucose toxicity. Glucose shortened the lifespan of C. elegans, while MAE suppressed the damage, accompanied by malondialdehyde (MDA) and triglyceride accumulation reduction as well as total superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity recovery and PMK-1/p38 expression promotion. In contrast, MAE failed to recover shortened longevity, glucose and triglyceride accumulation in daf-2 (−) mutants fed a glucose-supplemented diet. Transcriptional profile revealed MAE intervention led to 92 genes alteration compared with the glucose-treatment. Interestingly, expressions of DAF-2/insulin receptor related genes were increased by glucose but impaired by MAE in nematodes. Our studies suggested that MAE might help to improve the antioxidant defense system, resulting in prevention of glucose-induced damage both in vitro and in vivo.

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