Investigation of the Efficacy of Orientin in Streptozotocin-Induced Type 1 Diabetes Model and Pancreatic Beta-TC6 Cells.

Diabetes mellitus is a major endocrine disorder with rapidly increasing global prevalence and numerous systemic complications. Orientin, a flavonoid isolated from various medicinal plants, is known for its potent antioxidant and anti-inflammatory properties. This study evaluated the protective effects of Orientin in a streptozotocin (STZ)-induced type 1 diabetes model and in the pancreatic Beta-TC6 cell line. In the in vivo phase, 42 mice were randomly divided into seven groups, and diabetes was induced by a single intraperitoneal injection of STZ (160 mg/kg). Proinflammatory (IL-1β, IL-6) and anti-inflammatory (TGF-β, IL-10) cytokines were measured by ELISA. Pancreatic tissues were evaluated histopathologically (Masson's trichrome, Hematoxylin-eosin) and immunohistochemically (NF-κB p65), while oxidative stress parameters (SOD, CAT, GSH, and MDA) were analyzed. In addition, hepatic oxidative stress parameters were assessed, and liver tissues were examined using Periodic Acid-Schiff (PAS) staining. In vitro, the protective effects of Orientin against STZ-induced damage in Beta-TC6 cells were investigated. Apoptotic markers (Caspase-3, Caspase-9, Bax, and Bcl-2) were evaluated immunohistochemically, and pyroptotic markers (IL-1β and Caspase-1) were analyzed by ELISA. STZ-induced diabetes increased NF-κB immunopositivity, proinflammatory cytokines, and oxidative stress in pancreatic tissue. Orientin treatment reduced proinflammatory cytokines, increased anti-inflammatory cytokines, and improved oxidative stress parameters in both pancreatic and hepatic tissues. In Beta-TC6 cells, Orientin upregulated Bcl-2 and downregulated Bax, Caspase-3, Caspase-9, Caspase-1, and IL-1β levels. These findings suggest that Orientin protects against STZ-induced pancreatic damage by modulating oxidative stress, inflammation, apoptosis, and pyroptosis, supporting its potential as a therapeutic agent for preserving beta-cell integrity in diabetes.