Potential of syringol and guaiacol in mitigating hyperglycemia associated dicarbonyl stress in rats subjected to high-fat high-fructose diet

Objective The current study assessed the pharmacological potential of syringol and guaiacol, both separately and in combination, in hyperglycemia linked to dicarbonyl stress (DS). Methods The control group (n = 5) received a standard diet with Tween 20 and disease group received high-fat high-fructose diet. The remaining four groups received metformin, syringol (100 μg/kg), guaiacol (100 μg/kg), or a combination of both (50 + 50 μg/kg) starting on the 29th day and lasting 30 days. After study completion, glucose intolerance, oxidative stress markers, glycated products, liver, renal, lipid markers along with liver and pancreatic histology were assessed. NF-κB, TNF-α, IL-6, IL-1β, and nuclear factor erythroid 2-related factor 2 (Nrf2) expression levels were estimated using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). Key findings Combination therapy markedly decreased weight (31.30%), fasting blood glucose (74.92%), glucose intolerance (65.42%), and improved biochemical markers of lipid, hepatic, and renal function. The combination therapy significantly reduced (P < .05) malondialdehyde, nitric oxide, expression of NF-κB, TNF-α, IL-6, and IL-1β while increasing superoxide dismutase, catalase and reduced glutathione levels. Combination therapy significantly (P < .05) reduced HbA1c levels and increased Glo1, Glo2, and Nrf-2 levels. Histopathological variations showed reduced cellular damage in the treatment groups. Conclusion Combination of syringol and guaiacol exhibits significant pharmacological efficacy for managing DS associated with hyperglycemia.