Vol.:(0123456789) 1 3 Environmental Science and Pollution Research https://doi.org/10.1007/s11356-022-24568-3 RESEARCH ARTICLE Inhibition of dipeptidyl peptidase‑4 (DPP4), antioxidant, antiglycation and anti‑infammatory efect of Ferulic acid against streptozotocin toxicity mediate nephropathy in diabetic rats Maryam A. AL‑Ghamdi 1,2,3  · Said S. Moselhy 4 Received: 26 September 2022 / Accepted: 30 November 2022 © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022 Abstract The protein glycation due to high blood glucose mediate release of infammatory intermediate contributes in the development of diabetic nephropathy. Ferulic acid (FA) is a phenolic compound distributed in diferent foods as whole grains. Inhibitors of DPP4 improve GLP-1-mediated insulin secretion and inhibit liver gluconeogenesis. This study investigated the impact of FA as anti-infammatory, antioxidant and antiglycation against streptozotocin-induced diabetic nephropathy in rats. This study was carried out on total ninety male rats allocated into six (each 15 rats); group I (control). All other animals (groups II–VI) were receiving 65 mg/kg STZ for induction of diabetes. Rats in group II (untreated diabetic). Rats in groups III–V were treated with FA (10, 20, 30 mg/kg bw) respectively, i.p. for 8 weeks. Group VI received 10 units insulin daily, sc. Fasting blood samples were subjected for assay of glycated hemoglobin (HA1c), serum MDA, aldose reductase, total antioxidant, DPP4 while kidney tissue subjected for assay of malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), IL-1β and AGEs. Data obtained showed that, FA showed antioxidant activity by reducing MDA and enhancement antioxidant activity compared with untreated rats (p < 0.001) with dose dependence. In addition, FA reduced the activities of aldose reductase, DPP4 (p < 0.001), decreased IL-6, TNF-α and AGEs versus untreated rats (p < 0.001). Histological investigation revealed an improvement in the nephron structure in diabetic rat treated with FA versus untreated group. It was concluded that, FA possesses a potent antioxidant and anti- infammatory and DPP4 inhibitor. For that, it was considered as a protective agent against the risk of diabetic nephropathy and can be used as alternative or complementary supplement. Keywords Ferulic acid · Diabetic · DPP4 · Nephropathy · Infammation · AGES Introduction Diabetes mellitus (DM) is a chronic disease characterized by chronic high blood glucose level (Papadopoulou-Marketou et al. 2017). The incidence of disease increased worldwide and caused economical cost and health problems (Brouwers et al. 2010). Long-term uncontrolled and management led to serious complications as nephropathy. Diagnosis of disease in early stage is very important to avoid renal failure (Ahmed et al. 2005). Changes in the lifestyle, type of foods, physical activity, suitable medication (oral or insulin) all help in man- agement and avoid end stage of diseases. The patients should be aware by update knowledges for achievement of glycemic control in their lifestyle (McLellan et al. 1994). All hypo- glycemic agents (oral or insulin) may lead to side efects on long-term uses; for that, many investigations should be done regularly for follow-up on any changes (D’Agati et al. 2010). ResponsibleEditor: Lotf Aleya * Said S. Moselhy moselhy6@hotmail.com 1 Department of Biochemistry, Faculty of Science, King Abdulaziz University (KAU), Jeddah, Saudi Arabia 2 Vitamin D Pharmacogenomics Research Group, King Abdulaziz University (KAU), Jeddah 23623, Saudi Arabia 3 Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University (KAU), Jeddah 23623, Saudi Arabia 4 Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt