Ameliorative Role of a Plant-based Decoction in Streptozotocin-induced β-cell Damage: Targeting Oxidative Stress and the Nucleotide-binding Domain Leucine-rich Receptor, the Pyrin Domain Containing 3/Thioredoxin-interacting Protein Pathway

Abstract Objective: Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by insulin resistance, β-cell dysfunction, oxidative stress, and chronic inflammation. Oxidative stress activates thioredoxin-interacting protein (TXNIP), which activates the nucleotide-binding domain leucine-rich receptor, the pyrin domain containing 3 (NLRP3) inflammasome, promoting the release of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and IL-18. Streptozotocin (STZ)-induced models replicate these pathological features in vivo . Botanical mixtures rich in phytochemicals offer multitarget therapeutic potential by modulating oxidative and inflammatory pathways in T2DM. Methodology: This study investigated the antidiabetic potential of a combined extract of Rheum spiciforme and Bergenia stracheyi in an STZ-induced type 2 diabetic rat model, aiming to assess their synergistic efficacy. The therapeutic effects were evaluated through measurements of glucose regulation, oxidative stress markers, inflammatory mediators, and pancreatic histology. Results: The botanical mixture significantly reduced proinflammatory cytokines (IL-18, IL-1β, and TNF-α), as measured by enzyme-linked immunosorbent assay, and downregulated the gene expression of NLRP3 and TXNIP, indicating effective suppression of inflammatory pathways. Oxidative stress was alleviated through the upregulation of endogenous antioxidant defense mechanisms, evidenced by increased activities of superoxide dismutase, catalase, and elevated glutathione levels. Concurrently, a significant reduction in malondialdehyde indicated decreased lipid peroxidation. Histopathological analysis demonstrated protection of pancreatic islet architecture, with reduced β-cell damage, supporting the tissue-protective effects of the intervention. Conclusions: These findings suggest that the botanical mixture exerts potent antidiabetic effects through anti-inflammatory and antioxidant mechanisms, supporting β-cell preservation and improved metabolic regulation in T2DM.