Fermented seaweed extracts ameliorate diabetic nephropathy in streptozotocin-induced diabetic rats via PI3K/AKT/mTOR pathway

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The seaweed Laminaria japonica possesses a wide range of nutritional and medicinal properties, such as antioxidant and hypoglycemic effects. Previous research has demonstrated that fermenting Laminaria japonica with S. cerevisiae and Lactobacillus enhances its bioactivities. In this study, fermented Laminaria japonica underwent ethanol extraction to recover bioactive compounds. The impact of fermented seaweed extracts (FSE) on renal injury in streptozotocin-induced diabetic nephropathy rats was examined. Through UHPLC-MS/MS analysis, 44 compounds were identified in the fermented seaweed extracts, with carbohydrates and organic acids being the main classes. Fermented seaweed extracts significantly reduced streptozotocin-induced hyperglycemia, improved renal function markers (BUN, SCr, and Umalb), and mitigated kidney morphological changes. Specifically, the FSE-H group exhibited a 49% reduction in fasting glucose levels compared to the model group. Additionally, fermented seaweed extracts treatment downregulated both the transcriptional and protein levels of PI3K, Akt, and mTOR, suggesting involvement of the PI3K/AKT/mTOR-regulated pathway. These findings suggest that fermented seaweed extracts have potential as a therapeutic agent or functional ingredient for the treatment of diabetic nephropathy.