Synergistic Hypoglycemic Effect of Kalanchoe pinnata and Metformin in Oxidative Stress Management in Diabetes

Background: Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia and associated oxidative stress. This study aimed to evaluate the effects of aqueous extract of Kalanchoe pinnata and metformin, individually and in combination, on glucose levels, oxidative stress biomarkers, and pancreatic histology in alloxan-induced diabetic Wistar rats. Methods: Thirty male Wistar rats were divided into five groups (n=6): normal control, alloxan-induced positive control (metformin only), K. pinnata-treated, untreated diabetic control, and a combination of K. pinnata and metformin. Diabetes was induced using alloxan (150 mg/kg), and treatments were administered orally for 28 days. Blood glucose levels, body weights, serum antioxidant activities (SOD, CAT, GSH), lipid peroxidation (TBARS), and histological changes in the pancreas were assessed. Phytochemical analysis of K. pinnata extract was conducted. Results: Phytochemical analysis showed reductions in oxalates (0.97% to 0.40%), flavonoids (3.01% to 1.27%), and alkaloids (1.94% to 0.49%) post-extraction. Blood glucose levels in the K. pinnata-treated group decreased from 16.47±1.08 mmol/L on Day 1 to 14.83±1.47 mmol/L on Day 28, and in the combination group from 17.12±0.93 mmol/L to 15.27±1.35 mmol/L, but differences were not significant (p>0.05). Oxidative stress markers showed minor increases in SOD and CAT activity in the K. pinnata-treated group, but the changes were not significant. TBARS levels slightly reduced in both the K. pinnata and combination groups. Histological analysis showed severe β-cell destruction in the untreated diabetic group, mild restoration in the K. pinnata group, and moderate preservation in the metformin group, with slight improvements in the combination group, but no significant additive effects. Conclusion: While K. pinnata exhibited slight improvements in glucose levels, oxidative stress biomarkers, and partial histological recovery, the observed changes were not statistically significant. Further research using higher doses or longer treatment durations may better elucidate its therapeutic potential.