A Review of Preclinical Evidence and Translational Gaps

Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycaemia arising from impaired insulin secretion, insulin action, or both. Plant-derived products are investigated as possible sources of complementary antidiabetic agents because they contain chemically diverse constituents that may influence glucose regulation and diabetes-associated tissue injury. This review critically summarizes the preclinical evidence supplied for Azadirachta indica (neem) and Garcinia indica (kokum), with emphasis on glycaemic control, insulin-related pathways, oxidative stress, lipid abnormalities and organ-protective outcomes. Neem studies in chemically induced and diet-associated diabetic rodents report reductions in blood glucose, improvements in lipid indices, restoration of antioxidant enzymes and changes in insulin-signalling proteins. However, one neonatal streptozotocin model found that a 0.8% neem leaf preparation improved beta-cell morphology but did not restore glucose homeostasis, illustrating that outcomes depend on the model and preparation. Kokum studies report that aqueous fruit extract lowered fasting and postprandial glucose and restored erythrocyte glutathione in diabetic rats; other studies found glucose-, lipid- and renal-profile improvements with fruit-rind extracts, while a seed methanolic extract also reduced glucose in streptozotocin-treated rats. These findings are promising but remain preclinical. Differences in plant part, extraction solvent, dose, duration and diabetes model limit direct comparison. The evidence base lacks adequate standardization, pharmacokinetic characterization, long-term toxicology and controlled human efficacy data. Neither plant should be considered a proven substitute for established diabetes treatment. Further work should prioritize authenticated and chemically standardized extracts, reproducible dose-response studies, mechanistic validation, safety assessment and carefully designed clinical trials