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

TL;DR

This study finds that compounds from Moringa seeds protect kidney cells in diabetic nephropathy by altering metabolism and reducing inflammation.

Contribution

Two novel cyanoglycosides from Moringa seeds were identified and shown to protect against diabetic nephropathy through metabolic reprogramming.

Findings

Five compounds from Moringa seeds showed renoprotective effects in high-glucose-induced kidney cells.

The compounds suppressed oxidative stress, inflammation, and TGF-β1/Smad signaling while preserving mitochondrial function.

These effects were linked to metabolic reprogramming via modulation of PFKFB3 and inhibition of key signaling pathways.

Abstract

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.

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.

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.

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.

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.

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