Neuroprotective effects of black elderberry (Sambucus nigra) extract through the role of miR-124-5p and miR-144-5p in a streptozotocin-induced Type 2 diabetic rat model

Background: Type 2 diabetes mellitus (T2DM) leads to neurological complications through multiple pathways. Black elderberry (Sambucus nigra, SN) is rich in bioactive compounds with potential neuroprotective properties. This study sought to evaluate the neural-protective potential of SN extract in STZ-diabetic rats using an integrated molecular, biochemical, and histomorphological approach. Methods: Forty male Sprague-Dawley rats were divided into four groups (n = 10/group): control (C; 0.9% NaCl), SN (0.040 g/kg body weight), diabetes mellitus (DM; streptozotocin 50 mg/kg), and DM + SN (streptozotocin + SN). The treatment period was 10 weeks. Brain tissue was analyzed for histopathological changes, caspase-3 expression, microRNA (miRNA) expression, and oxidative stress markers. Results: Histopathological examination revealed severe neuronal degeneration in the DM group, significantly attenuated in the DM + SN group (p < 0.001). Caspase-3 immunoreactivity was markedly increased in DM group compared to controls and significantly reduced by SN treatment (p < 0.01). In situ hybridization showed high ribonucleic acid (rno)-miR-124-5p and rno-miR-144-5p expression in C and SN groups, with reduced expression in DM group (p < 0.05). SN treatment moderated these changes in DM + SN group. Quantitative real-time polymerase chain reaction (qRT-PCR) confirmed decreased miR-124 expression in DM group, restored to control levels by SN treatment. Biochemically, SN extract reversed diabetes-induced changes in oxidative stress markers, decreasing malondialdehyde (MDA) levels while increasing glutathione (GSH) and nitric oxide synthase (NOS) levels (p < 0.01). Conclusions: SN extract exerted robust neuroprotective actions in the diabetic brain through apoptosis inhibition, miRNA profile restoration, and amelioration of redox imbalance, underscoring its therapeutic promise for diabetes-associated neuropathy. © The Author(s), under exclusive licence to Springer Nature B.V. 2026.