Kolaviron Modulates Glucose Metabolism-associated Genes in Streptozotocin-Induced Diabetic Wistar Rats

Abstract

Background: Despite advances in diabetic treatment, side effects of antidiabetic drugs, including hypoglycemia and allergic reactions, drive the search for safer natural alternatives. Kolaviron (KV), a biflavonoid complex from Garcinia kola, has demonstrated antihyperglycemic properties, but its molecular impact on glucose metabolism-related genes remains understudied. This study aims to evaluate the effects of KV on Aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNT), Rat Insulin-2 (RATINS), Glucose transport type 4 (GLUT-4), and Toll-like receptor type 4 (TLR-4) gene expressions in streptozotocin-induced diabetic Wistar rats. Materials and Methods: A total of 22 adult male and female Wistar rats weighing 200–250 g were divided into five groups. Diabetes was induced in 20 rats using 42 mg/kg streptozotocin (STZ). Animals were grouped into five: Group A (non-diabetic control, n=2), Group B (untreated diabetic, n=2), Group C (diabetic, metformin 100 mg/kg, n=6), Group D (diabetic, KV 100 mg/kg, n=6), and Group E (diabetic, KV 200 mg/kg, n=6). Treatments lasted three months. Blood glucose and HbA1c were assessed monthly. mRNA expression of target genes was evaluated by qPCR. Sequence variations were analyzed using Sanger sequencing. Results: KV at 100 and 200 mg/kg body weight significantly reduced blood glucose and HbA1c levels (P<0.001). There was a significant upregulation of ARNT, RATINS, GLUT-4, and TLR-4 in KV-treated groups, with minor fluctuations in some months. A silent A→G mutation was detected at amino acid 885 of TLR-4 without altering protein function. Conclusion: KV improved glycemic control and modulated key genes in glucose metabolism without inducing harmful mutations, supporting its potential as a natural antidiabetic agent.