Insulin-Sensitizing Effect of Buchanania lanzan Leaf Extract: Integrated Computational and in vivo Evidence

Background: Buchanania lanzan Spreng. is a plant having anti-diabetic, anti-inflammatory properties. Aim: The aim of this research is to assess methanolic extract of Buchanania lanzan leaves for insulin sensitivity in diet induced insulin resistance rats and to elucidate the mechanisms of Buchanania lanzan phytoconstituents. Materials and Methods: Bioactive compounds from Buchanania lanzan were retrieved from phytochemical databases and published literature. Docking was performed using GNU Parallel-based pipeline- Parallelized Open Babel & AutoDock suite Pipeline. Diet-induced insulin resistance model was used to evaluate the Buchanania lanzan for insulin sensitivity followed by an oral glucose tolerance test, fasting glucose, and fasting insulin. Biochemical parameters such as glycogen content, glucose uptake, Tumor Necrosis Factor-α (TNF-α), antioxidant biomarkers, and lipid profiles were quantified along with histology study on the liver and pancreas. Results: Pathways enrichment analysis of 33 targets identified 14 molecular pathways associated with insulin resistance and its complications. It was found that the PI3K-Akt signaling pathway had the lowest false discovery rate and the highest gene count. Myricetin 3-galactoside-3'-rhamnoside (-8.9 kcal/mol), kaempferol-7-o’glucoside (-8.5 kcal/ mol), myricetin 3-galactoside-3'-rhamnoside (-7.6 kcal/mol) were identified as best hits against Peroxisome Proliferator-Activated Receptor Gamma (PPARG), Dipeptidyl Peptidase-4 (DPP4), and Protein Tyrosine Phosphatase Non-Receptor Type 1 (PTPN1) respectively that formed the highest interactions with active site residues compared to standard molecules. These results were correlated with the results of in-vivo study. Buchanania lanzan lowered elevated blood glucose levels by stimulating insulin secretion, played a vital role in preserving liver and islet cells, regulating glycolysis or gluconeogenesis, increasing glucose uptake in skeletal muscles, and decreasing TNF-α levels in serum. Conclusion: Results confirmed that Buchanania lanzan exhibit significant anti-insulin resistance, anti-inflammatory, anti-hyperlipidemic, anti-hyperglycemic, and antioxidant activities. These effects are likely ascribed to the presence of flavonoids in the leaves. Buchanania lanzan potentially modulate key proteins such as PPARG, DPP4, and PTPN1, thereby enhancing insulin sensitivity through the activation of the PI3K-Akt signaling pathway.