Potential molecular mechanisms underlying the ameliorative effect of Cola nitida (Vent.) Schott & Endl. on insulin resistance in rat skeletal muscles

Ethnopharmacological relevance: Cola nitida (Vent.) Schott & Endl. are among the common medicinal plants employed in traditional medicine for treating diabetes and its complications.Aim of the study: The present study investigated the effect of Cola nitida infusion on the expression of key genes involved in insulin signaling vis-`a-vis Insulin receptor substrate 1 (IRS-1), tumor protein P53 gene, glucose transporter type 4 (GLUT4), phosphoinositide 3-kinases (PI3K) and B-cell lymphoma-2 (BCL2) in skeletal muscles of type 2 diabetic (T2D) rats.Methods: Type 2 diabetic rats were administered C. nitida infusion at low and high doses (150 and 300 mg/kg bodyweight, respectively), while a high dose of the infusion was also administered to a normal toxicological group. Metformin served as the standard antidiabetic drug. The rats were sacrificed at the end of the experi-mental period. Their psoas muscles were harvested and assayed for the expressions of IRS1, p53, GLUT4, PI3K and BCL2. The studied genes were further subjected to enrichment analysis using the ShinyGO 0.76 online software.Results: Induction of T2D upregulated the expressions of IRS-1, p53, PI3K and BCL2 in psoas muscles, while concomitantly downregulating GLUT4 expression. These expressions were significantly reversed in type 2 dia-betic rats treated with C. nitida infusion, and the results were statistically significant compared to metformin. Gene enrichment analysis revealed that the genes were linked to intrinsic pathways and biological processes involved in insulin resistance. The infusion further improved muscle glucose uptake, ex vivo. Molecular docking and molecular dynamics stimulation of C. nitida infusion phytoconstituents, caffeine and theobromine with IRS -1, p53, GLUT4, PI3K and BCL2 revealed a strong binding affinity as evident by the RMSD and RMSF values.Conclusion: These results indicate the potentials of C. nitida infusion to improve glucose homeostasis in skeletal muscles of type 2 diabetic rats.