Beibei Zhang1, Mengnan Zeng1, Yangyang Wang2, Meng Li1, Yuanyuan Wu1, Ruiqi Xu1, Qinqin Zhang1, Jufang Jia1, Yanjie Huang3, Xiaoke Zheng4, Weisheng Feng5. 1. 156 Jinshui East Road, Henan University of Chinese Medicine, Zhengzhou 450046, China; The Engineering and Technology Center for Chinese Medicine Development of Henan Province, 156 Jinshui East Road, Zhengzhou 450046, China. 2. College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, China. 3. 156 Jinshui East Road, Henan University of Chinese Medicine, Zhengzhou 450046, China. 4. 156 Jinshui East Road, Henan University of Chinese Medicine, Zhengzhou 450046, China; The Engineering and Technology Center for Chinese Medicine Development of Henan Province, 156 Jinshui East Road, Zhengzhou 450046, China. Electronic address: zhengxk.2006@163.com. 5. 156 Jinshui East Road, Henan University of Chinese Medicine, Zhengzhou 450046, China; The Engineering and Technology Center for Chinese Medicine Development of Henan Province, 156 Jinshui East Road, Zhengzhou 450046, China. Electronic address: fwsh@hactcm.edu.cn.
Abstract
BACKGROUND: 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. AIMS: The research is aiming to probe the activities of OA on LPS-induced AKI. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: 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. AIMS: The research is aiming to probe the activities of OA on LPS-induced AKI. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Gloria Dávila-Ortiz; Erick Damian Castañeda-Reyes; Carlos Ignacio Juárez-Palomo; María de Jesús Perea-Flores; Ricardo Pérez-Pastén-Borja; Yazmín Karina Márquez-Flores; Elvira González de Mejía Journal: Int J Environ Res Public Health Date: 2022-09-16 Impact factor: 4.614