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

Sep 30, 2026

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Diabetic nephropathy is a major complication of diabetes, and Moringa oleifera seeds contain bioactive compounds with potential therapeutic value. This study isolated specific cyanoglycosides from the seeds and tested their renoprotective activity against high-glucose-induced diabetic nephropathy in hBZY-1 mesangial cells. The compounds’ effects were assessed on oxidative stress, inflammation, mitochondrial function, PFKFB3 expression, and the TGF-β1/Smad signaling pathway. Results showed two novel cyanoglycosides and three known compounds significantly improving renal injury markers while suppressing oxidative stress and inflammation, protecting mitochondria, modulating PFKFB3, and inhibiting TGF-β1/Smad-mediated metabolic dysregulation.

LanguageEnglish

CategoryHealthcare

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Pages13

Reading Time33 min

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Pharmaceutical Biology 2026, Vol. 64, No. 1, 130–142 [https://doi.org/10.1080/13880209.2025.2607563](https://doi.org/10.1080/13880209.2025.2607563) ReseaRch aRticle Cyanoglycosides isolated from Moringa oleifera seeds inhibited PFKFB3/TGF-β1/smads pathway to alleviate diabetic nephropathy through driving metabolic reprogramming chengyu Gea,b\#, Zhihua shic\#, Jia hea,b, Xu Fenga,b, Kaiqi shanga,b, Xiaolin liaoc, Yufeng liud, Yueping Jianga,b,c,e and shao liua,b aDepartment of Pharmacy, Xiangya hospital, central South university, changsha, hunan, china; bNational clinical research center for geriatric Disorders, Xiangya hospital, central South university, changsha, hunan, china; cDepartment of clinical Pharmacy, hunan university of medicine general hospital, huaihua, hunan, china; dcollege of Pharmacy, Jining medical university, rizhao, Shandong, china; ehunan Provincial Key laboratory of the research and Development of Novel Pharmaceutical Preparations,“the 14th Five-year Plan” application characteristic Discipline of hunan Province (Pharmaceutical Science), college of Pharmacy, changsha medical university, changsha, hunan, china ABSTRACT Context: Diabetic nephropathy (DN) is a major complication of diabetes. Moringaoleifera 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. Introduction ARTICLE HISTORY received 7 September 2025 revised 24 November 2025 accepted 16 December 2025 KEYWORDS Moringa oleifera seeds; cyanoglycosides; structure elucidation; diabetic nephropathy; metabolic reprogramming Diabetic nephropathy (DN), a serious complication of diabetes (Zhang et al. 2024), is the primary cause of end-stage renal disease worldwide (Patidar et al. 2024) . Its defining pathological feature is chronic kidney injury resulting from disrupted glucose metabolism (Chen et al. 2024) . DN progression manifests as proteinuria, which ultimately leads to renal interstitial fibrosis and glomerulosclerosis. Current first-line therapies predominantly target the renin-angiotensin system through CONTACT yueping Jiang [jiangyueping@csu.edu.cn](jiangyueping@csu.edu.cn) N

FAQs

What compounds were isolated from Moringa oleifera seeds in this study?

Four cyanoglycosides and one cyanoaglycone were isolated. Two cyanoglycosides were previously undescribed, while three were known compounds.

How were the renoprotective effects evaluated?

Renoprotective effects were assessed using an in vitro model of high-glucose-induced diabetic nephropathy in hBZY-1 mesangial cells.

Which mechanisms were investigated to explain the benefits?

Mechanistic studies examined oxidative stress, inflammation, mitochondrial function, glycolysis-related PFKFB3 expression, and inhibition of the TGF-β1/Smad signaling pathway.

Sep 30, 2026

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