18β-Glycyrrhetinic acid-loaded silver nanoparticles mitigate neuroinflammation and endoplasmic reticulum stress in the brain tissue of diabetic rats

Document Type : Original Article

Authors

1 Department of Histology and Embryology, Faculty of Medicine, Ağrı İbrahim Çeçen University, Agri, Turkey

2 Department of Histology and Embryology, Faculty of Veterinary Medicine, Mehmet Akif Ersoy University, Burdur, Turkey

3 Department of Molecular Biology and Genetics, Faculty of Science, Erzurum Technical University, Erzurum, Turkey

4 Department of Histology and Embryology, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan, Turkey

5 Department of Physiology, Faculty of Medicine, Atatürk University, Erzurum, Turkey

10.22038/ijbms.2025.86986.18801

Abstract

Objective(s): Diabetes mellitus (DM) causes oxidative stress, neuroinflammation, and endoplasmic reticulum (ER) dysfunction that contribute to neurodegeneration. This study investigated the effects of 18β-glycyrrhetinic acid-loaded silver nanoparticles (18β-GA-AgNPs) on brain injury in diabetic rats. 
Materials and Methods: Fifty-six male Wistar rats were divided into eight groups: Sham, 18β-GA, AgNPs, 18β-GA-AgNPs, DM, DM+18β-GA, DM+AgNPs, and DM+18β-GA-AgNPs. Diabetes was induced by alloxan (120 mg/kg, IP), and treatments were administered orally for 14 days. Biochemical markers (MDA, GSH, SOD), histopathology, and expression of ER stress and apoptotic proteins (ATF6, IRE1, Caspase-3, BCL-2, CREB, TNF-α, and IL-1β) were evaluated. 
Results: The DM group exhibited significant increases in MDA, TNF-α, IL-1β, ATF6, and Caspase-3 with reduced GSH, SOD, and BCL-2, indicating oxidative stress, inflammation, apoptosis, and ER stress. In contrast, IRE1 levels remained unchanged in DM rats but showed a slight elevation in the AgNPs group. Treatment with 18β-GA-AgNPs markedly reduced MDA, TNF-α, IL-1β, ATF6, and Caspase-3, while restoring GSH, SOD, BCL-2, and CREB expression. Histopathological analysis confirmed neuronal apoptosis and perivascular and extracellular space enlargement in DM rats, whereas 18β-GA-AgNPs substantially attenuated these changes. Overall, 18β-GA-AgNPs provided synergistic neuroprotection by suppressing oxidative stress, inflammation, and ER stress while enhancing antioxidant and anti-apoptotic defenses. 
Conclusion: These findings suggest that 18β-GA-AgNPs may represent a promising therapeutic strategy against diabetes-associated neurodegeneration, although further long-term, ultrastructural, and sex-inclusive studies are warranted.

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences
Volume 29, Issue 1
January 2026
Pages 81-89

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