Combined Effects of Eugenol and Ascorbic Acid on Glycemic Regulation and Transcriptional Modulation of Metabolic and Inflammatory Genes in Alloxan-Induced Diabetic Rats

Articles in Press

Document Type : Research Article

Authors

Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran

Abstract

Diabetes mellitus is characterized by hyperglycemia, oxidative stress, inflammation, and progressive β-cell dysfunction. Current therapies primarily focus on glycemic control and may not fully address these underlying mechanisms. Antioxidant compounds such as eugenol and L-ascorbic acid (vitamin C) have attracted attention as potential complementary approaches. However, their individual and combined effects on metabolic regulation and diabetes-related gene expression remain unclear. Therefore, this study aimed to investigate the effects of eugenol and vitamin C, alone and in combination, on glucose homeostasis and the expression of insulin-related, glucose transport-related, and inflammatory genes in pancreatic and hepatic tissues of diabetic rats. Rats were divided into five groups: healthy control, diabetic control, eugenol-treated (10 mg/kg/day; 0.25 mL of 10 mg/mL), vitamin C-treated (100 mg/kg/day; 0.25 mL of 30 mg/mL), and combination-treated groups. Treatments were administered for six weeks. Fasting blood glucose (FBG), body weight, and the expression levels of insulin-related (Ins1/2, Insr, Pdx1), glucose transport-related (Glut1, Glut2), and inflammation-related (Tnfα) genes in pancreatic and hepatic tissues were measured. The diabetic group showed persistently elevated blood glucose levels and reduced weight gain compared with the healthy controls. Vitamin C and eugenol treatments reduced glucose levels, with vitamin C showing a greater reduction (410 to 220 mg/dL) than eugenol (343.5 to 258.5 mg/dL). The vitamin C + eugenol group exhibited the largest absolute decline in FBG from baseline (471 to 275 mg/dL), although its final glucose concentration remained higher than that of the vitamin C-treated group (220 mg/dL). Body weight trends indicated that vitamin C supported mild weight gain, whereas eugenol was associated with weight loss, which was attenuated by combination therapy. Gene expression analysis revealed reduced Ins1/2, Insr, Glut2, and Pdx1 expression in diabetic rats, while combination therapy partially restored the expression of some investigated genes. Elevated Tnfα expression in diabetes was markedly reduced by eugenol and vitamin C, indicating potential anti-inflammatory effects. However, combination therapy increased hepatic Tnfα expression, highlighting tissue-specific differences in gene expression responses. Overall, eugenol and vitamin C, particularly when administered together, were associated with improved glycemic profiles and modulation of key metabolic, β-cell-associated, and inflammatory gene transcripts. However, these transcriptional alterations require further validation at the protein and functional levels.

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References

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