Oleic acid alleviates LPS-induced acute kidney injury by restraining inflammation and oxidative stress via the Ras/MAPKs/PPAR-γ signaling pathway

Rehmannia Glutinosa Libosch. is applied for the treatment of renal and inflammatory-related diseases, and oleic acid (OA) is a compound isolated from Rehmannia Glutinosa Libosch.. Unfortunately, the pharmacological activity of OA on LPS treated acute kidney injury (AKI) has not been investigated. The research is aiming to probe the activities of OA on LPS-induced AKI. Information of OA effect on AKI were from network pharmacology. H&E staining, creatinine (CRE) and urea nitrogen (UN) were performed to evaluate the activities of OA on kidney function. Inflammatory factors in serum were measured by cytometric bead array. Increased ratio of reactive oxygen species (ROS) in kidney and immune cells in the peripheral blood were determined by flow cytometry (FCM). PPAR-γ, MAPK and apoptotic signaling pathways were measured by Western blot. Then, a metabolomics approach was utilized to investigate OA's response to AKI. The role of salirasib (FTS, Ras inhibitor) in OA acted on ROS, Ca2+, MMP and Ras signaling pathway in LPS treated NRK-52e cells were investigated by FCM and In-cell western. It is proved that OA effetively ameliorated renal function, alleviated inflammatory response and oxidative stress, and transformed apoptotic, MAPK and PPAR-γ signaling pathways in mice with AKI, regulated phenylalanine metabolism, purine metabolism, sphingolipid metabolism, taurine and hypotaurine metabolism, moreover, the role of OA in injury of NRK-52e was blocked by FTS. In a word, OA could alleviate AKI by restraining inflammation and oxidative stress via regulating the Ras/MAPKs/PPAR-γ signaling pathway, phenylalanine metabolism, purine metabolism, sphingolipid metabolism and taurine and hypotaurine metabolism, which might be a useful strategy for treating AKI.