Multi-target antidiabetic and organ-protective effects of a polyherbal ethanol extract in STZ-induced diabetic rats

In diabetes mellitus conditions, hyperglycemia leads to oxidative stress, inflammation, and β-cell dysfunction, and traditional pharmacotherapy targets only a single pathway, which gives suboptimal outcomes and drug-related problems. A novel, polyherbal ethanol extract (PHE) formulation from Tinospora cordifolia, Commiphora wightii, Cinnamomum zeylanicum, and Paeonia officinalis was evaluated for antidiabetic and organ-protective effects at different levels for multi-targeting in a streptozotocin (STZ)-induced rat model.

Male Wistar rats were made diabetic using intraperitoneal administration of streptozotocin (55 mg/kg) and randomly segregated into five groups: Normal, STZ-induced diabetic, STZ + PHE (200 mg/kg/day), Normal + PHE, and STZ + metformin (Met; 300 mg/kg/day). After 8 weeks of treatment, FBG, HbA1c, insulin, lipid profile, proinflammatory cytokines (TNF-α, IL-1β), oxidative stress biomarkers, and liver function markers were determined. Histological examination was performed on liver and pancreatic tissues with H&E staining, along with assessment of pancreatic insulin immunoreactivity. GC-MS analysis was conducted to characterize the phytochemical constituents of PHE.

PHE treatment significantly reduced FBG by 33%, HbA1c by 15%, and restored serum insulin levels (+34%) versus untreated diabetics (p < 0.05). Dyslipidemia was corrected, with LDL-C reduced by 30% and HDL-C increased by 46%. Hepatic ALT and AST levels were also attenuated after PHE treatment. Oxidative stress was alleviated, and TNF-α and IL-1β levels in the liver and pancreas were markedly suppressed. Histology showed preserved hepatocyte integrity and islet morphology, and immunohistochemistry confirmed improved β-cell integrity and enhanced insulin immunoreactivity.

The polyherbal preparation produced impressive control over glycemia, strong antioxidant and anti-inflammatory effects, and protection of liver and pancreatic architecture. These effects translate into its potential as a phytotherapeutic candidate for safely managing diabetes and its complications, warranting further molecular and clinical research.