Cyanoglycosides isolated from Moringa oleifera seeds inhibited PFKFB3/TGF-β1/smads pathway to alleviate diabetic nephropathy through driving metabolic reprogramming.

CONTEXT: Diabetic nephropathy (DN) is a major complication of diabetes. Moringa oleifera seeds are recognized as a source of bioactive compounds with potential health benefits, prompting investigation into their specific components and effects on DN. OBJECTIVE: This study aimed to isolate bioactive compounds from M. oleifera seeds and evaluate their renoprotective effects and underlying mechanisms of action against high-glucose-induced diabetic nephropathy. MATERIALS AND METHODS: Four cyanoglycosides and one cyanoaglycone were isolated from M. oleifera seeds using chromatographic techniques. The renoprotective effects of these compounds were then evaluated using an in vitro model of high-glucose-induced diabetic nephropathy in HBZY-1 mesangial cells. Mechanistic studies further investigated the compounds' effects on oxidative stress, inflammation, mitochondrial function, expression of the glycolysis-related protein PFKFB3, and the TGF-β1/Smad signaling pathway. RESULTS: Two previously undescribed cyanoglycosides were isolated alongside three known compounds. All five compounds demonstrated significant renoprotective effects in the high-glucose-induced HBZY-1 cell model. Mechanistically, these effects were achieved by suppressing oxidative stress and inflammation, protecting mitochondrial function, modulating the expression of the glycolysis-related protein PFKFB3, and inhibiting the TGF-β1/Smad signaling pathway, collectively contributing to beneficial metabolic reprogramming. CONCLUSIONS: This study isolated two novel cyanoglycosides from M. oleifera seeds. These compounds, alongside known ones, protect against high-glucose-induced renal injury. Their renoprotection involves metabolic reprogramming via suppressing oxidative stress/inflammation, preserving mitochondrial function, modulating PFKFB3, and inhibiting TGF-β1/Smad signaling. These findings offer insights for utilizing M. oleifera seeds and suggest these cyanoglycosides as potential diabetic nephropathy therapeutics.