۱۸β-Glycyrrhetinic acid-loaded silver nanoparticles mitigate neuroinflammation and endoplasmic reticulum stress in the brain tissue of diabetic rats

Objective(s): Diabetes mellitus (DM) causes oxidative stress, neuroinflammation, and endoplasmic reticulum (ER) dysfunction that contribute to neurodegeneration. This study investigated the effects of ۱۸β-glycyrrhetinic acid-loaded silver nanoparticles (۱۸β-GA-AgNPs) on brain injury in diabetic rats. Materials and Methods: Fifty-six male Wistar rats were divided into eight groups: Sham, ۱۸β-GA, AgNPs, ۱۸β-GA-AgNPs, DM, DM+۱۸β-GA, DM+AgNPs, and DM+۱۸β-GA-AgNPs. Diabetes was induced by alloxan (۱۲۰ mg/kg, IP), and treatments were administered orally for ۱۴ days. Biochemical markers (MDA, GSH, SOD), histopathology, and expression of ER stress and apoptotic proteins (ATF۶, IRE۱, Caspase-۳, BCL-۲, CREB, TNF-α, and IL-۱β) were evaluated. Results: The DM group exhibited significant increases in MDA, TNF-α, IL-۱β, ATF۶, and Caspase-۳ with reduced GSH, SOD, and BCL-۲, indicating oxidative stress, inflammation, apoptosis, and ER stress. In contrast, IRE۱ levels remained unchanged in DM rats but showed a slight elevation in the AgNPs group. Treatment with ۱۸β-GA-AgNPs markedly reduced MDA, TNF-α, IL-۱β, ATF۶, and Caspase-۳, while restoring GSH, SOD, BCL-۲, and CREB expression. Histopathological analysis confirmed neuronal apoptosis and perivascular and extracellular space enlargement in DM rats, whereas ۱۸β-GA-AgNPs substantially attenuated these changes. Overall, ۱۸β-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 ۱۸β-GA-AgNPs may represent a promising therapeutic strategy against diabetes-associated neurodegeneration, although further long-term, ultrastructural, and sex-inclusive studies are warranted.

کلیدواژه ها:

Apoptosis ، Brain ، Diabetes Mellitus ، Endoplasmic reticulum - stress ، Glycyrrhetinic acid ، Neuroinflammation ، Oxidative stress ، Silver nanoparticles