Comparative Effects of Wild Hyperici Herba and <i>Hypericum perforatum</i> L. Hairy Root Extracts on Renal Carbohydrate Metabolism and Oxidative Stress in STZ-Induced Diabetic Rats

Abstract Chronic hyperglycemia-induced imbalances in renal carbohydrate metabolism and oxidative stress contribute to diabetic kidney complications, highlighting the urgent need for therapies targeting both pathways. This study evaluates nephroprotective effects of Hypericum perforatum L. extracts-wild Hyperici herba (HH) and hairy root (HR)-in streptozotocin-induced diabetic Wistar rats. Male Wistar rats received single intraperitoneal streptozotocin injection (45 mg/kg body weight) with diabetes confirmed by fasting blood glucose &gt;15 mmol/L. Diabetic rats were treated with daily oral doses of HH or HR extracts for 14 consecutive days. Renal carbohydrate metabolism was assessed through glycogen content, glucose levels, glucose-6-phosphate content, glucose-6-phosphatase and glucose-6-phosphate dehydrogenase activities. Oxidative stress markers evaluated included catalase, superoxide dismutase, glutathione reductase, glutathione peroxidase activities, total glutathione levels, and malondialdehyde (MDA) content. Diabetes induced 1.56-fold renal glucose increase, 1.7-fold glycogen accumulation, 47.5% higher glucose-6-phosphatase activity, 39.4% lower glucose-6-phosphate dehydrogenase activity, 44% catalase reduction, and elevated MDA levels. Both extracts significantly improved these parameters; HH reduced glucose-6-phosphatase by 33.1%, restored dehydrogenase by 61.5%; HR showed superior effects (37.5% and 67.3% respectively) plus normalized glycogen and enhanced catalase above controls. Glibenclamide had limited effects. Xanthone-enriched HR extract demonstrated superior nephroprotection versus HH and glibenclamide through comprehensive restoration of carbohydrate metabolism and antioxidant defenses in diabetic nephropathy.