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

Abstract

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.