Introduction: Diabetic nephropathy (DN), a global problem that threatens human health, is an important reason for chronic kidney disease and kidney failure. In our study, it was aimed to investigate the individual and combined effects of SA and EA in streptozotocin (STZ)-induced rats. Methods: The groups are as follows: Control, untreated diabetic, diabetic treated with Sinapic acid (SA), diabetic treated with Ellagic acid (EA), diabetic treated with SA and EA, treated with SA, treated with EA, and treated with SA and EA. Total kidney volume, total glomerulus volume, total filtration space volume, caspase-3, and 8-OHdG immunoreactivity, Malondialdehyde (MDA), Glutathione (GSH), Catalase (CAT), serum urea, and creatinine levels were evaluated by stereological, immunohistochemical, and biochemical methods. Results: The findings of the study showed that total kidney volume, total glomerulus volume, total filtration gap volume, caspase-3, and 8-OHdG immunoreactivity, MDA, serum urea, and creatinine levels significantly increased in the untreated diabetic group compared to the control group. Also, severe mesangial and glomerular enlargement, extracellular matrix accumulation, and glomerular and tubular basal membrane thickness were observed in the tubulointerstitial and glomerular of the diabetic rats. However, individual and combined treatments of SA and EA ameliorated these histological changes. Additionally, decreased GSH and CAT in the untreated diabetic group increased by SA and EA treatment. Conclusions: The findings suggest that treatment of SA and EA prevent apoptosis and DNA damage and structural changes in STZ-induced DN. However, the combined treatment of SA and EA were more effective than their individual treatments in all parameters except serum urea and creatinine.

Backgrounds: Scutellaria Pinnatifida subsp. pichleri (Stapf) Rech.f. (SP) is used in folk medicine for the treatment of diabetes. The aim of the study was to determine the phenolic profile of SP extract (SPE) by LC-MS/MS and to investigate the antidiabetic, hepatoprotective and nephroprotective effects of SPE in streptozotosin (STZ)-induced diabetic rat model. Methods: Forty-two rats were randomly divided into six groups (n = 7): Control (nondiabetic), diabetes mellitus (DM), DM + SP-100 (diabetic rats treated with SPE, 100 mg/kg/day), DM + SP-200 (diabetic rats treated with SPE, 200 mg/kg/day), DM + SP-400 (diabetic rats treated with SPE, 400 mg/kg/day) and DM + Gly-3 (diabetic rats treated with glibenclamide, 3 mg/kg/day). Live body weight, fasting blood glucose (FBG) level, antidiabetic, serum biochemical and lipid profile parameters, antioxidant defense system, malondyaldehyde (MDA) and histopathological examinations in liver, kidney and pancreas were evaluated. Results: Apigenin, luteolin, quinic acid, cosmosiin and epigallocatechin were determined to be the major phenolic compounds in the SPE. Administration of the highest dose of SP extract (400 mg/kg) resulted in a significant reduction in FBG levels and glycosylated hemoglobin levels in STZ-induced diabetic rats, indicating an antihyperglycemic effect. SPE (200 and 400 mg/kg) and glibenclamide significantly improved MDA in liver and kidney tissues. In addition, SPE contributed to the struggle against STZ-induced oxidative stress by stimulating antioxidant defense systems. STZ induction negatively affected liver, kidney and pancreas tissues according to histopathological findings. Treatment with 400 mg/kg and glibenclamide attenuated these negative effects. Conclusions: In conclusion, the extract of the aerial part of Scutellaria pinnatifida subsp. pichleri has hepatoprotective, nephroprotective and insulin secretion stimulating effects against STZ-induced diabetes and its complications due to its antidiabetic and antioxidant phytochemicals such as apigenin, luteolin, quinic acid, cosmosiin and epigallocatechin.