Protective effect of Qiukui Taoren Recipe against acute renal injury by inhibiting oxidative stress, inflammation and apoptotic pathways

Abstract

Okra and peach kernel, named Qiukui and Taoren in China, respectively, which can be used for medicine and food, are widely applied for the treatment of multifaceted diseases. However, the protective effects against acute kidney injury (AKI) and the underlying mechanisms have not been fully assessed. The aim of this study was to assess the protective effect of Qiukui Taoren Recipe (QT), and the potential molecular mechanisms in AKI using network pharmacology prediction, in vivo and in vitro experiment. There were 42 active components of QT detected by HPLC-Q-TOF/MS, and network pharmacology showed that these active components mainly could act with 63 core targets such as TNF-α, Caspase-3, BCL2, STAT3, PPARγ, and regulated 110 signaling pathways for alleviating AKI. In addition, QT reduced periocular oedema, renal malformations and size reduction, partially restore renal excretory function, and reduced the accumulation of proteinuria in zebrafish AKI model induced by caristolochic acid (AA). QT could upregulate the mRNA expression of Nephrin and oxidative stress genes (Nrf2, HO-1, PPARγ), and downregulate inflammation- and apoptosis-related genes (IL-1β, IL-6, TNF-α, NF-κB, Caspase-3, P53). Furthermore, QT inhibited ROS elevation and apoptosis activated by cisplatin (CDDP) in HEK293T cells. Western blotting results showed that QT could enhance the protein expression of nephrin, and inhibited the protein expression of Kim-1, IL-18, NLRP3, STAT3, P53 and Caspase-3. Overall, these results indicated the protective effect of QT against AKI was due to the inhibition of oxidative stress, inflammation-and apoptosis-related pathways.