Scutellarin protects the kidney from ischemia/reperfusion injury by targeting Nrf2. Issue 8 (15th June 2022) - Dai, Jie
Abstract: Background: Acute kidney injury (AKI) results in high morbidity and mortality among inpatients, while effective treatment and intervention are still absent. Therefore, this study aims to explore the effects of Scutellarin (Scu) in experimental models in vivo and in vitro. Methods: In vivo experiment, we employed a total of 30 Wistar rats, which further were modelled by a bilateral renal pedicle clip for 45 min, then received 50 mg/kg/day Scu. In vitro, HK‐2 cells were administered with 20μΜ Scu and then incubated in hypoxia/reoxygenation (H/R) conditions for 24 h. The knockdown of Nrf2 expression was conducted by small interfering RNA (siRNA) transfection. Results: As a result, the AKI model was well established with an increased SCr, BUN, KIM‐1 level, and histological injury score, while Scu treatment reduced the levels above and increased the antioxidative enzyme HO‐1. H/R induced an increase of ROS in HK‐2 cells, while Scu decreased the ROS level. Bioinformatics results showed the transcription factor Nrf2 was a hub protein during the AKI, which also bound to Scu with low binding energy, indicating that the downstream effect of Scu might be mediated by Nrf2. To verify the suppose above, we employed siRNA against Nrf2, which shows a significant increase in ROS after Nrf2 was blocked. Meanwhile, the HO‐1 showed similar expression compared with the 'H/R + Nrf2 siRNA' and 'H/R + Nrf2 siRNA + Scu' group, implying the protective effect of Scu was mediated by the Nrf2/HO‐1 pathway. Conclusion: Scu led to up‐regulation of HO‐1 through activating the Nrf2 signalling pathway, protecting the kidneys from ischemia/reperfusion (I/R)‐induced oxidative damage. Summary at a Glance: This study suggests that Scutellarin, a traditional Chinese medicine, protects the kidney from ischemia/reperfusion by reducing renal oxidative stress. By molecular docking and the knockdown of Nrf2, we verify that Scutellarin alleviates renal oxidative injury through the Nrf2/HO‐1 pathway.