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Journal of ethnopharmacology · 2026

Water-soluble anthocyanins from Vaccinium myrtillus L. alleviate diabetic kidney disease by targeting ALOX15-mediated lipid peroxidation.

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Sun Jie, Ding Xue, Zhang Yi-Han, Fan Huai-Min, Shi Ya-Li, Yan Chang-Yu, Huang Rui-Ting, Liu Fan-Na, He Rui-Kun, He Rong-Rong, Sun Wan-Yang

Аннотация

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic kidney disease (DKD) is a major diabetic complication with limited therapeutic options. Vaccinium myrtillus L. (bilberry) has a long history in European traditional medicine for treating microvascular disorders, inflammatory conditions, and urinary system ailments. As a traditional medicinal food rich in water-soluble anthocyanins, it has been reported to exert nephroprotective effects; however, its bioactive constituents and molecular mechanisms remain poorly defined.

AIM OF THE STUDY: This study aimed to investigate the renoprotective effects of a water-soluble anthocyanin-rich bilberry extract (VmE) in DKD, to identify its bioactive components, and to elucidate the underlying molecular mechanisms.

MATERIALS AND METHODS: A high-fat diet/streptozotocin-induced DKD mouse model was employed. The chemical profile of VmE was characterized by LC-MS. Renal function, histopathology, and metabolomics were evaluated. Integrated network pharmacology, molecular docking, microscale thermophoresis (MST), and molecular dynamics (MD) simulations were conducted to identify and validate key molecular targets.

RESULTS: VmE dose-dependently improved renal function, ameliorated tubulointerstitial injury, and restored metabolic homeostasis. Delphinidin-3-O-glucoside (Dp3Glc) and cyanidin-3-O-glucoside (Cy3Glc) were identified as the major anthocyanins. Both MST and MD simulations confirmed that Dp3Glc and Cy3Glc directly bind to arachidonate 15-lipoxygenase (ALOX15). This interaction inhibited ALOX15-mediated lipid peroxidation, resulting in reduced malondialdehyde (MDA) accumulation and iron overload, as well as restored glutathione (GSH) homeostasis, thereby attenuating ferroptosis in renal tubular cells.

CONCLUSIONS: VmE through its major anthocyanins Dp3Glc and Cy3Glc, alleviates DKD by directly targeting ALOX15 and suppressing lipid peroxidation-driven ferroptosis. These findings establish a pharmacological basis for developing VmE as a standardized nutraceutical for DKD management, bridging traditional use with modern mechanistic evidence.

Предметные рубрики MeSH

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты