Icariin Attenuates Renal Injury in Streptozotocin-Induced Diabetic Rats with and Without Adenine-Induced Chronic Kidney Disease

Background: Diabetes mellitus (DM) and chronic kidney disease (CKD) are major contributors to global morbidity and mortality, with disease progression being closely linked to persistent inflammation, oxidative damage, and apoptotic pathways. Icariin (ICA), a bioactive flavonoid compound isolated from Epimedium brevicornum Maxim, has attracted considerable interest because of its diverse pharmacological properties. We evaluated the effect of ICA on streptozotocin (STZ)-induced diabetic rats with or without adenine-induced CKD. This combined model reproduces several key structural and functional characteristics observed in human diabetic kidney disease and advanced CKD. Methods: Male Wistar rats were allocated to five treatment groups and followed for 35 days. Group 1 served as the untreated control and received standard chow; Group 2 was administered streptozotocin (STZ); Group 3 received STZ together with icariin (ICA); Group 4 received a combination of adenine and STZ; and Group 5 was treated with adenine, STZ, and ICA. ICA was administered at a dose of 200 mg/kg by oral gavage. Biochemical, oxidative stress and inflammatory markers were assessed. Results: Rats treated with STZ, with or without adenine, exhibited significant hyperglycemia, elevated plasma levels of cystatin C and indoxyl sulphate, increased urinary levels of N-acetyl-β-D-glucosaminidase (NAG) and NAG/creatinine ratio, and reduced creatinine clearance. Additionally, there were significant decreases in renalase activity and urine osmolality, significant increases in interleukins IL-1β and IL-6 and TNF-alpha levels, and a decrease in IL-10 level. Oxidative stress biomarkers were also significantly impaired in both groups, along with significant renal histopathological changes. ICA significantly ameliorated these alterations in both experimental groups. Conclusions: These findings demonstrate that ICA exerts renoprotective and anti-inflammatory effects in a clinically relevant model of advanced diabetic CKD. Further studies are warranted to elucidate the underlying mechanisms and determine the translational relevance of these findings.